Many studies have shown the positive impact of serious educational games (SEGs) on learning outcomes. However, there still exists insufficient research that delves into the impact of immersive ...experience in the process of gaming on SEG‐based science learning. The dual purpose of this study was to further explore this impact. One purpose was to develop and validate an innovative measurement, the Game Immersion Questionnaire (GIQ), and to further verify the hierarchical structure of game immersion by construct validity approaches, including exploratory factor analysis (EFA) (n = 257) and confirmatory factor analysis (CFA) (n = 1044). The second purpose was to investigate the impact of game immersion on science learning through SEG play (n = 260). Overall, the results supported the internal structure of the GIQ with good reliability and validity, and the inter factor bivariate correlations for each construct indicated a high internal consistency. Players did learn from playing an SEG, and game immersion experience did lead to higher gaming performance. Moreover, players' gaming performance plays a role in mediating the effect of immersion on science learning outcomes through SEG play. However, as players became more emotionally and subjectively attached to the game, the science learning outcomes were not definitively reliable.
We calculated the organic matter to organic carbon mass ratios (OM/OC mass ratios) in PM2.5 collected from 14 Chinese cities during summer and winter of 2003 and analyzed the causes for their ...seasonal and spatial variability. The OM/OC mass ratios were calculated two ways. Using a mass balance method, the calculated OM/OC mass ratios averaged 1.92 ± 0.39 year-round, with no significant seasonal or spatial variation. The second calculation was based on chemical species analyses of the organic compounds extracted from the PM2.5 samples using dichloromethane/methanol and water. The calculated OM/OC mass ratio in summer was relatively high (1.75 ± 0.13) and spatially-invariant due to vigorous photochemistry and secondary organic aerosol (OA) production throughout the country. The calculated OM/OC mass ratio in winter (1.59 ± 0.18) was significantly lower than that in summer, with lower values in northern cities (1.51 ± 0.07) than in southern cities (1.65 ± 0.15). This likely reflects the wider usage of coal for heating purposes in northern China in winter, in contrast to the larger contributions from biofuel and biomass burning in southern China in winter. On average, organic matter constituted 36% and 34% of Chinese urban PM2.5 mass in summer and winter, respectively. We report, for the first time, a high regional correlation between Zn and oxalic acid in Chinese urban aerosols in summer. This is consistent with the formation of stable Zn oxalate complex in the aerosol phase previously proposed by Furukawa and Takahashi (2011). We found that many other dicarboxylic acids were also highly correlated with Zn in the summer Chinese urban aerosol samples, suggesting that they may also form stable organic complexes with Zn. Such formation may have profound implications for the atmospheric abundance and hygroscopic properties of aerosol dicarboxylic acids.
Summary
Healthcare workers involved in aerosol‐generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID‐19. However, the magnitude of this risk is unknown. We ...conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID‐19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self‐reporting. The primary endpoint was the incidence of laboratory‐confirmed COVID‐19 diagnosis or new symptoms requiring self‐isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure‐related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR range) follow‐up of 32 (18–48 0–116) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID‐19 subsequently reported a COVID‐19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID‐19 transmission.
Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained ...with the Candida albicans cell wall constituent β-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1α (hypoxia-inducible factor-1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1α pathway represents the metabolic basis of trained immunity.
Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct ...patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.
Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment.
We ...selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample.
Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10(-37) and P=2.52×10(-37), respectively) and in the replication sample of 100 patients (P=9.19×10(-15) for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing.
Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).
Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms ...involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
Vibrational spectroscopy allows us to understand complex physical and chemical interactions of molecular crystals and liquids such as ammonia, which has recently emerged as a strong hydrogen fuel ...candidate to support a sustainable society. We report inelastic neutron scattering measurement of vibrational properties of ammonia along the solid-to-liquid phase transition with high enough resolution for direct comparisons to ab-initio simulations. Theoretical analysis reveals the essential role of nuclear quantum effects (NQEs) for correctly describing the intermolecular spectrum as well as high energy intramolecular N-H stretching modes. This is achieved by training neural network models using ab-initio path-integral molecular dynamics (PIMD) simulations, thereby encompassing large spatiotemporal trajectories required to resolve low energy dynamics while retaining NQEs. Our results not only establish the role of NQEs in ammonia but also provide general computational frameworks to study complex molecular systems with NQEs.
Colonic fermentation of dietary fibre to short-chain fatty acids (SCFA) influences appetite hormone secretion in animals, but SCFA production is excessive in obese animals. This suggests there may be ...resistance to the effect of SCFA on appetite hormones in obesity.
To determine the effects of inulin (IN) and resistant starch (RS) on postprandial SCFA, and gut hormone (glucagon-like peptide (GLP-1), peptide-tyrosine-tyrosine (PYY) and ghrelin) responses in healthy overweight/obese (OWO) vs lean (LN) humans.
Overnight-fasted participants (13 OWO and 12 LN) consumed 300 ml water containing 75 g glucose (GLU) as control or 75 g GLU plus 24 g IN, or 28.2 g RS using a randomised, single-blind, cross-over design. Blood for appetite hormones and SCFA was collected at intervals over 6 h. A standard lunch was served 4 h after the test drink.
Relative to GLU, IN, but not RS, significantly increased SCFA areas under the curve (AUC) from 4-6 h (AUC
). Neither IN nor RS affected GLP-1 or PYY-AUC
. Although neither IN nor RS reduced ghrelin-AUC
compared with GLU, ghrelin at 6 h after IN was significantly lower than that after GLU (P<0.05). After IN, relative to GLU, the changes in SCFA-AUC
were negatively related to the changes in ghrelin-AUC
(P=0.017). SCFA and hormone responses did not differ significantly between LN and OWO.
Acute increases in colonic SCFA do not affect GLP-1 or PYY responses in LN or OWO subjects, but may reduce ghrelin. The results do not support the hypothesis that SCFA acutely stimulate PYY and GLP-1 secretion; however, a longer adaptation to increased colonic fermentation or a larger sample size may yield different results.
Little is known about the biological mechanisms underpinning the pathology of schizophrenia. We have analysed the proteome of stimulated and unstimulated peripheral blood mononuclear cells (PBMCs) ...from schizophrenia patients and controls as a potential model of altered cellular signaling using liquid-chromatography mass spectrometry proteomic profiling. PBMCs from patients and controls were stimulated for 72 h in vitro using staphylococcal enterotoxin B. In total, 18 differentially expressed proteins between first-onset, antipsychotic-naive patients and controls in the unstimulated and stimulated conditions were identified. Remarkably, eight of these proteins were associated with the glycolytic pathway and patient-control differences were more prominent in stimulated compared with unstimulated PBMCs. None of these proteins were altered in chronically ill antipsychotic-treated patients. Non-linear multivariate statistical analysis showed that small subsets of these proteins could be used as a signal for distinguishing first-onset patients from controls with high precision. Functional analysis of PBMCs did not reveal any difference in the glycolytic rate between patients and controls despite increased levels of lactate and the glucose transporter-1, and decreased levels of the insulin receptor in patients. In addition, subjects showed increased serum levels of insulin, consistent with the idea that some schizophrenia patients are insulin resistant. These results show that schizophrenia patients respond differently to PBMC activation and this is manifested at disease onset and may be modulated by antipsychotic treatment. The glycolytic protein signature associated with this effect could therefore be of diagnostic and prognostic value. Moreover, these results highlight the importance of using cells for functional discovery and show that it may not be sufficient to measure protein expression levels in static states.