We introduce a Feasible Artificial Intelligence with Simple Trajectories for Predicting Adverse Catastrophic Events (FAST-PACE) solution for preparing immediate intervention in emergency situations. FAST-PACE utilizes a concise set of collected features to construct an artificial intelligence model that predicts the onset of cardiac arrest or acute respiratory failure from 1 h to 6 h prior to its occurrence. Data from the trajectory of 29,181 patients in intensive care units of two hospitals includes periodic vital signs, a history of treatment, current health status, and recent surgery. It excludes the results of laboratory data to construct a feasible application in wards, out-hospital emergency care, emergency transport, or other clinical situations where instant medical decisions are required with restricted patient data. These results are superior to previous warning scores including the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS). The primary outcome was the feasibility of an artificial intelligence (AI) model predicting adverse events 1 h to 6 h prior to occurrence without lab data; the area under the receiver operating characteristic curve of this model was 0.886 for cardiac arrest and 0.869 for respiratory failure 6 h before occurrence. The secondary outcome was the superior prediction performance to MEWS (net reclassification improvement of 0.507 for predicting cardiac arrest and 0.341 for predicting respiratory failure) and NEWS (net reclassification improvement of 0.412 for predicting cardiac arrest and 0.215 for predicting respiratory failure) 6 h before occurrence. This study suggests that AI consisting of simple vital signs and a brief interview could predict a cardiac arrest or acute respiratory failure 6 h earlier.
This paper presents an empirical exploration of the use of capsule networks for text classification. While it has been shown that capsule networks are effective for image classification, their validity in the domain of text has not been explored. In this paper, we show that capsule networks indeed have potential for text classification, and that they have several advantages over convolutional neural networks. We further suggest a simple routing method that effectively reduces the computational complexity of dynamic routing. We utilized seven benchmark datasets to demonstrate that capsule networks, along with the proposed routing method provide comparable results.
We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8, thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquitination and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast, a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together, our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.
Manuscript 2 AbsrtactThe marine red alga Porphyra yezoensis has been proposed as a model plant for physiological and genetic studies in seaweeds because of its biological and economical importance. However, the progress of molecular biological studies using gene transfection and genetic transformation systems has been hindered by difficulties in the expression of foreign genes in P. yezoensis cells. To overcome this situation, we developed a transient gene expression system to monitor gene expression in P. yezoensis cells. An artificial -glucuronidase (GUS) coding region was synthesized to adapt it to the codon usage of P. yezoensis (PyGUS) and then evaluated for efficiency as a reporter of transient gene expression by particle bombardment. We also demonstrated the importance of using the promoter of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene from P. yezoensis for efficient expression of PyGUS, because the cauliflower mosaic virus (CaMV) 35S promoter, which has been successfully used for monitoring gene expression in nuclei and chloroplasts of higher plants, was less active in P. yezoensis cells. Therefore, the lack of knowledge about differences in the regulatory machinery of gene expression between P. yezoensis and terrestrial plants seems to be why experimental systems for monitoring gene expression were previously not developed in P. yezoensis. Establishment of the transient gene expression system in P. yezoensis could facilitate biotechnological developments in this organism.3
We investigated whether cognitive decline could be explained by resting-state electroencephalography (EEG) biomarkers measured in prefrontal regions that reflect the slowing of intrinsic EEG oscillations. In an aged population dwelling in a rural community (total = 496, males = 165, females = 331), we estimated the global cognitive decline using the Mini-Mental State Examination (MMSE) and measured resting-state EEG parameters at the prefrontal regions of Fp1 and Fp2 in an eyes-closed state. Using a tertile split method, the subjects were classified as T3 (MMSE 28–30, N = 162), T2 (MMSE 25–27, N = 179), or T1 (MMSE ≤ 24, N = 155). The EEG slowing biomarkers of the median frequency, peak frequency and alpha-to-theta ratio decreased as the MMSE scores decreased from T2 to T1 for both sexes (−5.19 ≤ t-value ≤ −3.41 for males and −7.24 ≤ t-value ≤ −4.43 for females) after adjusting for age and education level. Using a double cross-validation procedure, we developed a prediction model for the MMSE scores using the EEG slowing biomarkers and demographic covariates of sex, age and education level. The maximum intraclass correlation coefficient between the MMSE scores and model-predicted values was 0.757 with RMSE = 2.685. The resting-state EEG biomarkers showed significant changes in people with early cognitive decline and correlated well with the MMSE scores. Resting-state EEG slowing measured in the prefrontal regions may be useful for the screening and follow-up of global cognitive decline in elderly individuals.
The development of complex organs such as the eye requires a delicate and coordinated balance of cell division and cell death. Although apoptosis is prevalent in the proximoventral optic cup, the precise role it plays in eye development needs to be investigated further. In this study, we show that reduced apoptosis in the proximoventral optic cup prevents closure of the optic fissure. We also show that expression of ephrin A5 (Efna5) partially overlaps with Eph receptor B2 (Ephb2) expression in the proximoventral optic cup and that binding of EphB2 to ephrin A5 induces a sustained activation of JNK. This prolonged JNK signal promotes apoptosis and prevents cell proliferation. Thus, we propose that the unique cross-subclass interaction of EphB2 with ephrin A5 has evolved to function upstream of JNK signaling for the purpose of maintaining an adequate pool of progenitor cells to ensure proper closure of the optic fissure.
Endocytosis of Eph-ephrin complexes may be an important mechanism for converting cell-cell adhesion to a repulsive interaction. Here, we show that an endocytosisdefective EphA8 mutant forms a complex with EphAs and blocks their endocytosis in cultured cells. Further, we used bacterial artificial chromosome transgenic (Tg) mice to recapitulate the anterior4posterior gradient of EphA in the superior colliculus (SC). In mice expressing the endocytosis-defective EphA8 mutant, the nasal axons were aberrantly shifted to the anterior SC. In contrast, in Tg mice expressing wild-type EphA8, the nasal axons were shifted to the posterior SC, as predicted for the enhanced repellent effect of ephrinA reverse signalling. Importantly, Rac signalling was shown to be essential for EphAephrinA internalization and the subsequent nasal axonal repulsion in the SC. These results indicate that endocytosis of the Eph-ephrin complex is a key mechanism by which axonal repulsion is generated for proper guidance and topographic mapping.
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