68 research outputs found
Explainable Deep Learning for Disease Activity Prediction in Chronic Inflammatory Joint Diseases
Leveraging Token-Based Concept Information and Data Augmentation in Few-Resource NER: ZuKyo-EN at the NTCIR-16 Real-MedNLP task
In this paper, we discuss our contribution to the NII Testbeds and Community for Information Access Research (NTCIR) - 16 Real- MedNLP shared task. Our team (ZuKyo) participated in the English subtask: Few-resource Named Entity Recognition. The main challenge in this low-resource task was a low number of training documents annotated with a high number of tags and attributes. For our submissions, we used different general and domain-specific transfer learning approaches in combination with multiple data augmentation methods. In addition, we experimented with models enriched with biomedical concepts encoded as token-based input feature
Approach for Named Entity Recognition and Case Identification Implemented by ZuKyo-JA Sub-team at the NTCIR-16 Real-MedNLP Task
In this NTCIR-16 Real-MedNLP shared task paper, we present the methods of the ZuKyo-JA subteam for solving the Japanese part of Subtask1 and Subtask3 (Subtask1-CR-JA, Subtask1-RR- JA, Subtask3-RR-JA). Our solution is based on a sliding- window approach using a Japanese BERT pre-trained masked- language model., which was used as a common architecture for addressing the specific subtasks. We additionally present a method that makes extensive use of medical knowledge for the same case identification subtask3-RR-JA
The role of epigenetics in renal ageing
An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects
The protein mat(ters)-revealing the biologically relevant mechanical contribution of collagen- and fibronectin-coated micropatterns
Understanding cell-material interactions requires accurate characterization of the substrate mechanics, which are generally measured by indentation-type atomic force microscopy. To facilitate cell-substrate interaction, model extracellular matrix coatings are used although their tensile mechanical properties are generally unknown. In this study, beyond standard compressive stiffness estimation, we performed a novel tensile mechanical characterization of collagen- and fibronectin-micropatterned polyacrylamide hydrogels. We further demonstrate the impact of the protein mat on the tensile stiffness characterization of adherent cells. To our knowledge, our study is the first to uncover direction-dependent mechanical behavior of the protein coatings and to demonstrate that it affects cellular response relative to substrate mechanics
Focus on time: dynamic imaging reveals stretch-dependent cell relaxation and nuclear deformation
Among the stimuli to which cells are exposed in vivo, it has been shown that tensile deformations induce specific cellular responses in musculoskeletal, cardiovascular, and stromal tissues. However, the early response of cells to sustained substrate-based stretch has remained elusive because of the short timescale at which it occurs. To measure the tensile mechanical properties of adherent cells immediately after the application of substrate deformations, we have developed a dynamic traction force microscopy method that enables subsecond temporal resolution imaging of transient subcellular events. The system employs a novel, to our knowledge, tracking approach with minimal computational overhead to compensate substrate-based, stretch-induced motion/drift of stretched single cells in real time, allowing capture of biophysical phenomena on multiple channels by fluorescent multichannel imaging on a single camera, thus avoiding the need for beam splitting with the associated loss of light. Using this tool, we have characterized the transient subcellular forces and nuclear deformations of single cells immediately after the application of equibiaxial strain. Our experiments reveal significant differences in the cell relaxation dynamics and in the intracellular propagation of force to the nuclear compartment in cells stretched at different strain rates and exposes the need for time control for the correct interpretation of dynamic cell mechanics experiments
Green fluorescent protein transformation sheds more light on a widespread mycoparasitic interaction
Powdery mildews, ubiquitous obligate biotrophic plant pathogens, are often attacked in the field by mycoparasitic fungi belonging to the genus Ampelomyces. Some Ampelomyces strains are commercialized biocontrol agents of crop pathogenic powdery mildews. Using Agrobacterium tumefaciens-mediated transformation (ATMT), we produced stable Ampelomyces transformants that constitutively expressed green fluorescent protein (GFP) to (i) improve the visualization of the mildew–Ampelomyces interaction and (ii) decipher the environmental fate of Ampelomyces fungi before and after acting as a mycoparasite. Detection of Ampelomyces structures, and especially hyphae, was greatly enhanced when diverse powdery mildew, leaf, and soil samples containing GFP transformants were examined with fluorescence microscopy compared with brightfield and differential interference contrast optics. We showed for the first time, to our knowledge, that Ampelomyces strains can persist up to 21 days on mildew-free host plant surfaces, where they can attack powdery mildew structures as soon as these appear after this period. As saprobes in decomposing, powdery mildew-infected leaves on the ground and also in autoclaved soil, Ampelomyces strains developed new hyphae but did not sporulate. These results indicate that Ampelomyces strains occupy a niche in the phyllosphere where they act primarily as mycoparasites of powdery mildews. Our work has established a framework for a molecular genetic toolbox for the genus Ampelomyces using ATMT
Shear-stress sensing by PIEZO1 regulates tendon stiffness in rodents and influences jumping performance in humans
Athletic performance relies on tendons, which enable movement by transferring forces from muscles to the skeleton. Yet, how load-bearing structures in tendons sense and adapt to physical demands is not understood. Here, by performing calcium (Ca2+) imaging in mechanically loaded tendon explants from rats and in primary tendon cells from rats and humans, we show that tenocytes detect mechanical forces through the mechanosensitive ion channel PIEZO1, which senses shear stresses induced by collagen-fibre sliding. Through tenocyte-targeted loss-of-function and gain-of-function experiments in rodents, we show that reduced PIEZO1 activity decreased tendon stiffness and that elevated PIEZO1 mechanosignalling increased tendon stiffness and strength, seemingly through upregulated collagen cross-linking. We also show that humans carrying the PIEZO1 E756del gain-of-function mutation display a 13.2% average increase in normalized jumping height, presumably due to a higher rate of force generation or to the release of a larger amount of stored elastic energy. Further understanding of the PIEZO1-mediated mechanoregulation of tendon stiffness should aid research on musculoskeletal medicine and on sports performance
Modulation of inhibitory control by prefrontal anodal tDCS: A crossover double-blind sham-controlled fMRI study
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