High-resolution short-term prediction of the COVID-19 epidemic based on spatial-temporal model modified by historical meteorological data.

In the global challenge of Coronavirus disease 2019 (COVID-19) pandemic, accurate prediction of daily new cases is crucial for epidemic prevention and socioeconomic planning. In contrast to traditional local, one-dimensional time-series data-based infection models, the study introduces an innovative approach by formulating the short-term prediction problem of new cases in a region as multidimensional, gridded time series for both input and prediction targets. A spatial-temporal depth prediction model for COVID-19 (ConvLSTM) is presented, and further ConvLSTM by integrating historical meteorological factors (Meteor-ConvLSTM) is refined, considering the influence of meteorological factors on the propagation of COVID-19. The correlation between 10 meteorological factors and the dynamic progression of COVID-19 was evaluated, employing spatial analysis techniques (spatial autocorrelation analysis, trend surface analysis, etc.) to describe the spatial and temporal characteristics of the epidemic. Leveraging the original ConvLSTM, an artificial neural network layer is introduced to learn how meteorological factors impact the infection spread, providing a 5-day forecast at a 0.01° × 0.01° pixel resolution. Simulation results using real dataset from the 3.15 outbreak in Shanghai demonstrate the efficacy of Meteor-ConvLSTM, with reduced RMSE of 0.110 and increased R 2 of 0.125 (original ConvLSTM: RMSE = 0.702, R 2 = 0.567; Meteor-ConvLSTM: RMSE = 0.592, R 2 = 0.692), showcasing its utility for investigating the epidemiological characteristics, transmission dynamics, and epidemic development.

Estimation of near-surface ozone concentration and analysis of main weather situation in China based on machine learning model and Himawari-8 TOAR data.

Ozone (O3) is an important greenhouse gas in the atmosphere. Stratospheric ozone protects human beings, but high near-surface ozone concentrations threaten environment and human health. Owing to the uneven distribution of ground-monitoring stations and the low time resolution of polar orbiting satellites, it is difficult to accurately evaluate the refinement and synergistic pollution of near-surface ozone in China. Besides, atmospheric circulation patterns also affect ozone concentrations greatly. In this study, a new generation of geostationary satellite is used to estimate the hourly near-surface ozone concentration with a spatial resolution of 0.05°. First, the Pearson correlation coefficient and maximum information coefficient were used to study the correlation between the top of atmospheric radiation (TOAR) of Himawari-8 satellite and O3 concentration; seven TOAR channels were selected. Second, based on an interpretable deep learning model, the hourly ozone concentration in China from September 2015 to August 2021 was obtained using the TOAR-O3 model. Finally, the self-organizing map method was used to determine six major summer weather circulation patterns in China. The results showed that (1) the near-surface O3 concentration can be accurately estimated; the R2 (RMSE: µg/m3) values of the daily, monthly, and annual tenfold cross validation results were 0.91 (12.74), 0.97 (5.64), and 0.98 (1.75), respectively. The feature importance of the model showed that the temperature, TOAR, and boundary layer height contributed 38 %, 22 %, and 13 %, respectively. (2) The O3 concentration showed obvious spatiotemporal difference and gradually increased from 10:00 to 15:00 (Beijing time) every day. In most areas of China, O3 concentration had increased significantly. (3) The O3 concentration in northern China was the highest under the circulation pattern of the Meiyu front over the Yangtze River Delta, while in southern China, it was the highest under the circulation pattern of the northeast cold vortex controlling most of China.

Effects of nurse-led multidisciplinary team management on cardiovascular hospitalization and quality of life in patients with atrial fibrillation: Randomized controlled trial.

BACKGROUND: Atrial fibrillation is globally the most common sustained cardiac arrhythmia which increases patient morbidity and mortality, dramatically influencing well-being. Despite substantial efforts, an optimal clinical pathway for chronic atrial fibrillation management has yet to be developed. In recent practice, a multidisciplinary team management has been recommended for patients with atrial fibrillation. However, experiments exploring nurse-led multidisciplinary team management in chronic atrial fibrillation management relative to standard clinical management are still sparse and limited. OBJECTIVE: To evaluate the effects of a nurse-led multidisciplinary team approach on cardiovascular hospitalization and death, and quality of life in patients with atrial fibrillation. DESIGN: Randomized controlled trial. SETTING: The Cardiology Department of a tertiary referral hospital in Beijing, China. PARTICIPANTS: Eligible patients diagnosed with atrial fibrillation who consented. METHODS: Subjects were randomly assigned into one of two Cardiology Units upon admission. Patients in the control group (n = 119) received usual care and those in the intervention group (n = 116) underwent a nurse-led multidisciplinary team approach. Follow-up lasted for 12 months. The primary endpoint was a composite of cardiovascular hospitalization and cardiovascular death. The secondary endpoint was the differences in the quality of life between the groups observed at 6 months and 12 months of follow-up, compared to the baseline data, as determined using a Chinese version of the Medical Outcome Study Short-Form 36 General Health Survey. RESULTS: Patients under intervention showed a fewer cardiovascular hospitalization (17 vs. 35, p = 0.006) than those receiving usual care. Discernible differences were also observed in rates of cardiovascular hospitalization between the two groups (hazard ratio: 2.115, 95% confidential interval: 1.228-3.643, log-rank = 6.746, p = 0.009). Quality of life was improved in both groups, but more so in the intervention group (scores, 588.0 ± 106.0 vs. 519.1 ± 120.7 at 6 months and 674.4 ± 53.4 vs. 584.1 ± 105.9 at 12 months; both p < 0.001). Repeated measures analysis of variance indicated that group-by-time and between-subjects effects in respect of patients' quality of life (F = 9.310, p < 0.01; F = 29.042, p < 0.01, respectively). No relationships were found with cardiovascular death. CONCLUSIONS: Nurse-led multidisciplinary team management reduces cardiovascular hospitalization and improves quality of life in patients with atrial fibrillation, suggesting that this innovative management approach should be implemented in clinical practice. REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1800018851).

Efficacy of pressure ulcer prevention interventions in adult intensive care units: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Pressure ulcers (PUs) are associated with substantial health burden. Patients in intensive care units (ICUs) are at high risk for developing PU. In the absence of large randomised controlled trials (RCTs) that compare commonly known interventions for preventing PU in ICUs, uncertainty remains around the best practice strategy for PU management in adult ICUs. This study, therefore, aims to identify the most effective interventions and combinations of interventions that prevent PU in adult ICU using systematic review and network meta-analysis (NMA). METHODS AND ANALYSIS: We will search for all published and unpublished RCTs evaluating interventions to prevent PU compared with other PU prevention measures or with usual care in adult ICU. The primary outcomes are the incidence of PUs and PU severity in critically ill patients in ICU. The secondary outcomes include number of PUs per patient and intervention-related harms caused by the prevention intervention or intervention-related harms. All data extraction will be performed by at least two independent reviewers on the basis of a priori developed extraction form. We will evaluate the risk of bias of the included RCTs in accordance with the Cochrane Collaboration's risk of bias tool, and assess the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation. A standard pairwise meta-analysis and a Bayesian NMA will be conducted to compare the efficacy of different PU prevention interventions. A surface under the cumulative ranking curve will be used to rank the probabilities of each prevention intervention for various outcomes. ETHICS AND DISSEMINATION: This study will not require the ethics approval as it is a review based on published studies. The findings of this study will be submitted to a peer-reviewed journal for publication. We anticipate that the results of the study will provide the evidence to inform clinicians and guideline developers on determining the best interventions for the prevention of PU in ICU patients. PROSPERO REGISTRATION NUMBER: CRD42018085562.

Association of two proteolipids of unknown function with ATP synthase from bovine heart mitochondria.

ATP synthase, or F-ATPase, purified from bovine heart mitochondria in the absence of phospholipids is an assembly of 16 different subunits. In the presence of exogenous phospholipids, two additional hydrophobic proteins, a 6.8kDa proteolipid and diabetes associated protein in insulin sensitive tissue (DAPIT), were associated with the purified complex, with DAPIT at sub-stoichiometric levels. Both proteins are conserved in vertebrates and invertebrates, but not in fungi, and prokaryotic F-ATPases do not contain orthologues of either of them. Therefore, their roles are likely to be peripheral to the synthesis of ATP.

AMPylation targets the rate-limiting step of BiP's ATPase cycle for its functional inactivation.

The endoplasmic reticulum (ER)-localized Hsp70 chaperone BiP contributes to protein folding homeostasis by engaging unfolded client proteins in a process that is tightly coupled to ATP binding and hydrolysis. The inverse correlation between BiP AMPylation and the burden of unfolded ER proteins suggests a post-translational mechanism for adjusting BiP's activity to changing levels of ER stress, but the underlying molecular details are unexplored. We present biochemical and crystallographic studies indicating that irrespective of the identity of the bound nucleotide AMPylation biases BiP towards a conformation normally attained by the ATP-bound chaperone. AMPylation does not affect the interaction between BiP and J-protein co-factors but appears to allosterically impair J protein-stimulated ATP-hydrolysis, resulting in the inability of modified BiP to attain high affinity for its substrates. These findings suggest a molecular mechanism by which AMPylation serves as a switch to inactivate BiP, limiting its interactions with substrates whilst conserving ATP.

AMPylation matches BiP activity to client protein load in the endoplasmic reticulum.

The endoplasmic reticulum (ER)-localized Hsp70 chaperone BiP affects protein folding homeostasis and the response to ER stress. Reversible inactivating covalent modification of BiP is believed to contribute to the balance between chaperones and unfolded ER proteins, but the nature of this modification has so far been hinted at indirectly. We report that deletion of FICD, a gene encoding an ER-localized AMPylating enzyme, abolished detectable modification of endogenous BiP enhancing ER buffering of unfolded protein stress in mammalian cells, whilst deregulated FICD activity had the opposite effect. In vitro, FICD AMPylated BiP to completion on a single residue, Thr(518). AMPylation increased, in a strictly FICD-dependent manner, as the flux of proteins entering the ER was attenuated in vivo. In vitro, Thr(518) AMPylation enhanced peptide dissociation from BiP 6-fold and abolished stimulation of ATP hydrolysis by J-domain cofactor. These findings expose the molecular basis for covalent inactivation of BiP.

G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases.

Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selectivity. However, selectivity was restored by crude cell lysate or purified G-actin, which joined PPP1R15-PP1 to form a stable ternary complex. In crystal structures of the non-selective PPP1R15B-PP1G complex, the functional core of PPP1R15 made multiple surface contacts with PP1G, but at a distance from the active site, whereas in the substrate-selective ternary complex, actin contributes to one face of a platform encompassing the active site. Computational docking of the N-terminal lobe of eIF2a at this platform placed phosphorylated serine 51 near the active site. Mutagenesis of predicted surface-contacting residues enfeebled dephosphorylation, suggesting that avidity for the substrate plays an important role in imparting specificity on the PPP1R15B-PP1G-actin ternary complex.

The phosphorylation of subunits of complex I from bovine heart mitochondria.

In bovine heart mitochondria and in submitochondrial particles, membrane-associated proteins with apparent molecular masses of 18 and 10 kDa become strongly radiolabeled by [(32)P]ATP in a cAMP-dependent manner. The 18-kDa phosphorylated protein is subunit ESSS from complex I and not as previously reported the 18 k subunit (with the N-terminal sequence AQDQ). The phosphorylated residue in subunit ESSS is serine 20. In the 10 kDa band, the complex I subunit MWFE was phosphorylated on serine 55. In the presence of protein kinase A and cAMP, the same subunits of purified complex I were phosphorylated by [(32)P]ATP at the same sites. Subunits ESSS and MWFE both contribute to the membrane arm of complex I. Each has a single hydrophobic region probably folded into a membrane spanning alpha-helix. It is likely that the phosphorylation site of subunit ESSS lies in the mitochondrial matrix and that the site in subunit MWFE is in the intermembrane space. Subunit ESSS has no known role, but subunit MWFE is required for assembly into complex I of seven hydrophobic subunits encoded in the mitochondrial genome. The possible effects of phosphorylation of these subunits on the activity and/or the assembly of complex I remain to be explored.

Lysine 43 is trimethylated in subunit C from bovine mitochondrial ATP synthase and in storage bodies associated with batten disease.

The hydrophobic membrane protein, subunit c, has been isolated from ATP synthase purified from bovine heart mitochondria. It has also been obtained from lysosomal storage bodies associated with ceroid lipofuscinosis from ovine liver and from human brain tissue of a victim of Batten disease. It is likely that the lysosomal protein has originated from the mitochondrion. These samples have been characterized by mass spectrometric methods. Irrespective of its source, subunit c has an intact molecular mass of 7650 Da, 42 Da greater than the value calculated from the amino acid sequence, and the protein has been modified post-translationally. In all three samples, the modification is associated with lysine 43, which lies in a polar loop region linking the two transmembrane alpha-helices of the protein. This residue is conserved throughout vertebrate sequences. The additional mass arises from trimethylation and not acetylation at the epsilon-N-position of the residue. These experiments show that the post-translational modification of subunit c is not, as has been suggested, an abnormal phenomenon associated with the etiology of Batten disease and ceroid lipofucinoses. Evidently, it occurs either before or during import of the protein into mitochondria or at a mitochondrial location after completion of the import process. The function of the trimethyllysine residue in the assembled ATP synthase complex is obscure. The residue and the modification are not conserved in all ATP synthases, and their role in the assembly and (or) functioning of the enzyme appear to be confined to higher organisms.