Application of a Machine Learning Algorithms in a Wrist-Wearable Sensor for Patient Health Monitoring during Autonomous Hospital Bed Transport.

Smart sensors, coupled with artificial intelligence (AI)-enabled remote automated monitoring (RAMs), can free a nurse from the task of in-person patient monitoring during the transportation process of patients between different wards in hospital settings. Automation of hospital beds using advanced robotics and sensors has been a growing trend exacerbated by the COVID crisis. In this exploratory study, a polynomial regression (PR) machine learning (ML) RAM algorithm based on a Dreyfusian descriptor for immediate wellbeing monitoring was proposed for the autonomous hospital bed transport (AHBT) application. This method was preferred over several other AI algorithm for its simplicity and quick computation. The algorithm quantified historical data using supervised photoplethysmography (PPG) data for 5 min just before the start of the autonomous journey, referred as pre-journey (PJ) dataset. During the transport process, the algorithm continued to quantify immediate measurements using non-overlapping sets of 30 PPG waveforms, referred as in-journey (IJ) dataset. In combination, this algorithm provided a binary decision condition that determined if AHBT should continue its journey to destination by checking the degree of polynomial (DoP) between PJ and IJ. Wrist PPG was used as algorithm's monitoring parameter. PPG data was collected simultaneously from both wrists of 35 subjects, aged 21 and above in postures mimicking that in AHBT and were given full freedom of upper limb and wrist movement. It was observed that the top goodness-of-fit which indicated potentials for high data accountability had 0.2 to 0.6 cross validation score mean (CVSM) occurring at 8th to 10th DoP for PJ datasets and 0.967 to 0.994 CVSM at 9th to 10th DoP for IJ datasets. CVSM was a reliable metric to pick out the best PJ and IJ DoPs. Central tendency analysis showed that coinciding DoP distributions between PJ and IJ datasets, peaking at 8th DoP, was the precursor to high algorithm stability. Mean algorithm efficacy was 0.20 as our proposed algorithm was able to pick out all signals from a conscious subject having full freedom of movement. This efficacy was acceptable as a first ML proof of concept for AHBT. There was no observable difference between subjects' left and right wrists.

IKKε isoform switching governs the immune response against EV71 infection.

The reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNß and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens.

Enterovirus 71 Infection Shapes Host T Cell Receptor Repertoire and Presumably Expands VP1-Specific TCRß CDR3 Cluster.

Enterovirus 71 (EV71) has become an important public health problem in the Asia-Pacific region in the past decades. EV71 infection might cause neurological and psychiatric complications and even death. Although an EV71 vaccine has been currently approved, there is no effective therapy for treating EV71-infected patients. Virus infections have been reported to shape host T cell receptor (TCR) repertoire. Therefore, understanding of host TCR repertoire in EV71 infection could better the knowledge in viral pathogenesis and further benefit the anti-viral therapy development. In this study, we used a mouse-adapted EV71 (mEV71) model to observe changes of host TCR repertoire in an EV71-infected central nervous system. Neonate mice were infected with mEV71 and mouse brainstem TCRß repertoires were explored. Here, we reported that mEV71 infection impacted host brainstem TCRß repertoire, where mEV71 infection skewed TCRß diversity, changed VJ combination usages, and further expanded specific TCRß CDR3 clones. Using bioinformatics analysis and ligand-binding prediction, we speculated the expanded TCRß CDR3 clone harboring CASSLGANSDYTF sequence was capable of binding cleaved EV71 VP1 peptides in concert with major histocompatibility complex (MHC) molecules. We observed that mEV71 infection shaped host TCRß repertoire and presumably expanded VP1-specific TCRß CDR3 in mEV71-infected mouse brainstem that integrated EV71 pathogenesis in central nervous system.

Host relieves lnc-IRAK3-3-sequestered miR-891b to attenuate apoptosis in Enterovirus 71 infection.

Enterovirus 71 (EV71) is an emerging life-threatening pathogen particularly in the Asia-Pacific region. Apoptosis is a major pathogenic feature in EV71 infection. However, which molecular mechanism participating in EV71-induced apoptosis is not completely understood. Long noncoding RNAs (lncRNAs), a newly discovered class of regulatory RNA molecules, govern a wide range of biological functions through multiple regulatory mechanisms. Whether lncRNAs involved in EV71-induced apoptosis was investigated in this study. We conducted an apoptosis-oriented approach by integrating lncRNA and mRNA profilings. lnc-IRAK3-3 is down-regulated in EV71 infection and plays an important role in EV71 infection-induced apoptosis. Compensation of lnc-IRAK3-3 in EV71 infection promoted cell apoptosis wherein GADD45ß expression was increased and further triggered caspase3 and PARP cleavage. Using bioinformatics analysis and functional assays, lnc-IRAK3-3 could functionally sequester miR-891b and GADD45ß 3'UTR whereas miR-891b showed the inhibitory activity on GADD45ß expression. Taken together, lnc-IRAK3-3 has the ability capturing miR-891b to enforce GADD45ß expression and eventually promotes apoptosis. On the contrary, host cells suppress lnc-IRAK3-3 to relieve lnc-IRAK3-3-sequestered miR-891b, restrain GADD45ß, and attenuate apoptosis in EV71 infection that prevent host cells from severe damages. We discover a new molecular mechanism by which host cells counteract EV71-induced apoptosis through the lnc-IRAK3-3/miR-891b/GADD45ß axis partially.