GenHPF: General Healthcare Predictive Framework for Multi-task Multi-source Learning.

Despite the remarkable progress in the development of predictive models for healthcare, applying these algorithms on a large scale has been challenging. Algorithms trained on a particular task, based on specific data formats available in a set of medical records, tend to not generalize well to other tasks or databases in which the data fields may differ. To address this challenge, we propose General Healthcare Predictive Framework (GenHPF), which is applicable to any EHR with minimal preprocessing for multiple prediction tasks. GenHPF resolves heterogeneity in medical codes and schemas by converting EHRs into a hierarchical textual representation while incorporating as many features as possible. To evaluate the efficacy of GenHPF, we conduct multi-task learning experiments with single-source and multi-source settings, on three publicly available EHR datasets with different schemas for 12 clinically meaningful prediction tasks. Our framework significantly outperforms baseline models that utilize domain knowledge in multi-source learning, improving average AUROC by 1.2%P in pooled learning and 2.6%P in transfer learning while also showing comparable results when trained on a single EHR dataset. Furthermore, we demonstrate that self-supervised pretraining using multi-source datasets is effective when combined with GenHPF, resulting in a 0.6 pretraining. By eliminating the need for preprocessing and feature engineering, we believe that this work offers a solid framework for multi-task and multi-source learning that can be leveraged to speed up the scaling and usage of predictive algorithms in healthcare.1.

Distinct dynamics of the nucleolus in response to nutrient availability and during development in the rice blast fungus.

IMPORTANCE: The nucleolus is a dynamic subnuclear structure that is involved in many fundamental processes of the nucleus. In higher eukaryotic cells, the size and shape of nucleoli correlate with nucleolar activities. For fungi, knowledge of the nucleolus and its functions is primarily gleaned from budding yeast. Whether such correlation is conserved and how nucleolar functions are regulated in filamentous fungi including important human and crop pathogens are largely unknown. Our observations reveal that the dynamics of nucleolus in a model plant pathogenic fungus, Magnaporthe oryzae, is distinct from those of animal and yeast nucleoli under low nutrient availability and during pathogenic development. Our data not only provide new insight into the nucleoli in filamentous fungi but also highlight the need for investigating how nucleolar dynamics is regulated in comparison to other eukaryotes.

Plasmonic-Magnetic Active Nanorheology for Intracellular Viscosity.

We demonstrate active plasmonic systems where plasmonic signals are repeatedly modulated by changing the orientation of nanoprobes under an external magnetic field, which is a prerequisite for in situ active nanorheology in intracellular viscosity measurements. Au/Ni/Au nanorods act as "nanotransmitters", which transmit the mechanical motion of nanorods to an electromagnetic radiation signal as a periodic sine function. This fluctuating optical response is transduced to frequency peaks via Fourier transform surface plasmon resonance (FTSPR). As a driving frequency of the external magnetic field applied to the Au/Ni/Au nanorods increases and reaches above a critical threshold, there is a transition from the synchronous motion of nanorods to asynchronous responses, leading to the disappearance of the FTSPR peak, which allows us to measure the local viscosity of the complex fluids. Using this ensemble-based method with plasmonic functional nanomaterials, we measure the intracellular viscosity of cancer cells and normal cells in a reliable and reproducible manner.

Large-Scale Screening of the Plant Extracts for Antifungal Activity against the Plant Pathogenic Fungi.

Plants produce chemicals of immense diversity that provide great opportunities for development of new antifungal compounds. In search for environment-friendly alternatives to the fungicide of current use, we screened plant extracts obtained from more than eight hundred plant materials collected in Korea for their antifungal activity against the model plant pathogenic fungus, Magnaporthe oryzae. This initial screening identified antifungal activities from the eleven plant extract samples, among which nine showed reproducibility in the follow-up screening. These nine samples were able to suppress not only M. oryzae but also other fungal pathogens. Interestingly, the plant extracts obtained from Actinostemma lobatum comprised five out of eight samples, and were the most effective in their antifungal activity. We found that butanol fraction of the A. lobatum extract is the most potent. Identification and characterization of antifungal substances in the A. lobatum extracts would provide the promising lead compounds for new fungicide.

A Histone Deacetylase, Magnaporthe oryzae RPD3, Regulates Reproduction and Pathogenic Development in the Rice Blast Fungus.

Acetylation and deacetylation of histones are key epigenetic mechanisms for gene regulation in response to environmental stimuli. RPD3 is a well-conserved class I histone deacetylase (HDAC) that is involved in diverse biological processes. Here, we investigated the roles of the Magnaporthe oryzae RPD3 (MoRPD3) gene, an ortholog of Saccharomyces cerevisiae Rpd3, during development and pathogenesis in the model plant-pathogenic fungus Magnaporthe oryzae. We demonstrated that the MoRPD3 gene is able to functionally complement the yeast Rpd3 deletion mutant despite the C-terminal extension of the MoRPD3 protein. MoRPD3 localizes primarily to the nuclei of vegetative hyphae, asexual spores, and invasive hyphae. Deletion of MoRPD3 appears to be lethal. Depletion of MoRPD3 transcripts via gene silencing (MoRPD3kd, where "kd" stands for "knockdown") has opposing effects on asexual and sexual reproduction. Although conidial germination and appressorium formation rates of the mutants were almost comparable to those of the wild type, in-depth analysis revealed that the appressoria of mutants are smaller than those of the wild type. Furthermore, the MoRPD3kd strain shows a significant reduction in pathogenicity, which can be attributed to the delay in appressorium-mediated penetration and impaired invasive growth. Interestingly, MoRPD3 does not regulate potassium transporters, as shown for Rpd3 of S. cerevisiae. However, it functioned in association with the target of rapamycin (TOR) kinase pathway, resulting in the dependency of appressorium formation on hydrophilic surfaces and on TOR's inhibition by MoRPD3. Taken together, our results uncovered distinct and evolutionarily conserved roles of MoRPD3 in regulating fungal reproduction, infection-specific development, and virulence. IMPORTANCE RPD3 is an evolutionarily conserved class I histone deacetylase (HDAC) that plays a pivotal role in diverse cellular processes. In filamentous fungal pathogens, abrogation of the gene encoding RPD3 results in either lethality or severe growth impairment, making subsequent genetic analyses challenging. Magnaporthe oryzae is a causal agent of rice blast disease, which is responsible for significant annual yield losses in rice production. Here, we characterized the RPD3 gene of M. oryzae (MoRPD3) in unprecedented detail using a gene-silencing approach. We provide evidence that MoRPD3 is a bona fide HDAC regulating fungal reproduction and pathogenic development by potentially being involved in the TOR-mediated signaling pathway. To the best of our knowledge, this work is the most comprehensive genetic dissection of RPD3 in filamentous fungal pathogens. Our work extends and deepens our understanding of how an epigenetic factor is implicated in the development and virulence of fungal pathogens of plants.

Au nanolenses for near-field focusing.

We report a novel strategy for the synthesis of Pt@Au nanorings possessing near-field focusing capabilities at the center through which single-particle surface enhanced Raman scattering could be readily observed. We utilized Pt@Au nanorings as a light-absorber; the absorbed light could be focused at the center with the aid of a Au nanoporous structure. We synthesized the Au nanolens structure through a Galvanic exchange process between Au ions and Ag block at the inner domain of the Pt@Au nanoring. For this step, Ag was selectively pre-deposited at the inner domain of the Pt@Au nanorings through electrochemical potential-tuned growth control and different surface energies with regard to the inner and outer boundaries of the nanoring. Then, the central nanoporous architecture was fabricated through the Galvanic exchange of sacrificial Ag with Au ions leading to the resulting Au nanoring with a Au nanoporous structure at the center. We monitored the shape-transformation by observing their corresponding localized surface plasmon resonance (LSPR) profiles. By varying the rim thickness of the starting Pt@Au nanorings, the inner diameter of the nanolens was accordingly tuned to maximize near-field focusing, which enabled us to obtain the reproducible and light-polarization independent measurements of single-particle SERS. Through theoretical simulation, the near-field electromagnetic field focusing capability was visualized and confirmed through single-particle SERS measurement showing an enhancement factor of 1.9 × 108 to 1.0 × 109.