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Background and Objective Sleep is an important physiological process for humans. Students of tertiary institutions, especially those at the university, are often reported to have poor sleep quality due to changing social opportunities and increasing academic demands. This study aimed to investigate the prevalence of poor sleeping quality and its relationship with academic performance and psychological distress among university students in Malaysia.Methods An online questionnaire-based, cross-sectional study was conducted among students of tertiary institutions in Malaysia. The questionnaire consisted of respondents’ demographics, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Horne-Ostberg Morningness-Eveningness Scale (MES) and Depression-Anxiety-Stress Scales (DASS-21). Simple and multiple linear regression were used to identify the relationship between the independent and dependent variables (PSQI score and MES score).Results Of the 403 respondents, about three-fourths were poor-quality sleepers. The cumulative grade point average (CGPA) was the only factor with a significant linear and positive relationship with the PSQI score. Only the depression and anxiety scores showed a significant linear and positive relationship between the PSQI score and the MES score.Conclusions Poor sleep quality was prevalent among university students. Poor sleep was associated with better academic performance. Students with depression or anxiety were significantly associated with poor sleep quality and being a morning bird.

To investigate the influence of executive function (EF) on current and future quality of life (QoL) and negative emotion (NE) in older adults with diabetes.A total of 128 older adults with diabetes were recruited. Independent variables (demographic information, health and medical conditions, cognitive function, life function) were collected in the first year. Dependent variables (QoL and NE) were collected for 3 years. Pearson's correlation coefficient analysis and stepwise multiple linear regression analysis were performed to identify the predictors of QoL and NE.EF was the strongest predictor for overall QoL and NE in all 3 years, and accounted for 23.0-36.2% and 11.1-17.1% of the variance, respectively. The second strongest predictor for overall QoL in all 3 years was pain interference, which accounted for 3.2-5.8% of the variance. Pain interference was also the second strongest predictor for NE in the second year, accounting for 5.5% of the variance.The present study revealed that EF is more predictive than pain for current and future QoL and NE in older adults with diabetes. We recommend that EF be included as an indicator for diabetes surveillance, and that prevention of EF decline be a part of diabetes management plans.

ObjectiveGastric cancer (GC) comprises multiple molecular subtypes. Recent studies have highlighted mesenchymal-subtype GC (Mes-GC) as a clinically aggressive subtype with few treatment options. Combining multiple studies, we derived and applied a consensus Mes-GC classifier to define the Mes-GC enhancer landscape revealing disease vulnerabilities.DesignTranscriptomic profiles of ~1000 primary GCs and cell lines were analysed to derive a consensus Mes-GC classifier. Clinical and genomic associations were performed across >1200 patients with GC. Genome-wide epigenomic profiles (H3K27ac, H3K4me1 and assay for transposase-accessible chromatin with sequencing (ATAC-seq)) of 49 primary GCs and GC cell lines were generated to identify Mes-GC-specific enhancer landscapes. Upstream regulators and downstream targets of Mes-GC enhancers were interrogated using chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing, CRISPR/Cas9 editing, functional assays and pharmacological inhibition.ResultsWe identified and validated a 993-gene cancer-cell intrinsic Mes-GC classifier applicable to retrospective cohorts or prospective single samples. Multicohort analysis of Mes-GCs confirmed associations with poor patient survival, therapy resistance and few targetable genomic alterations. Analysis of enhancer profiles revealed a distinctive Mes-GC epigenomic landscape, withTEAD1as a master regulator of Mes-GC enhancers and Mes-GCs exhibiting preferential sensitivity to TEAD1 pharmacological inhibition. Analysis of Mes-GC super-enhancers also highlightedNUAK1kinase as a downstream target, with synergistic effects observed between NUAK1 inhibition and cisplatin treatment.ConclusionOur results establish a consensus Mes-GC classifier applicable to multiple transcriptomic scenarios. Mes-GCs exhibit a distinct epigenomic landscape, and TEAD1 inhibition and combinatorial NUAK1 inhibition/cisplatin may represent potential targetable options.

Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects through a prospective 10-year study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as small clonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of somatic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident “pseudoantralized” subtype associated with incomplete histology, antral/intestinal cell types,ARID1Amutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical- genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.

Gastric cancer heterogeneity represents a barrier to disease management. We generated a comprehensive single-cell atlas of gastric cancer (>200,000 cells) comprising 48 samples from 31 patients across clinical stages and histologic subtypes. We identified 34 distinct cell-lineage states including novel rare cell populations. Many lineage states exhibited distinct cancer-associated expression profiles, individually contributing to a combined tumor-wide molecular collage. We observed increased plasma cell proportions in diffuse-type tumors associated with epithelial-resident KLF2 and stage-wise accrual of cancer-associated fibroblast subpopulations marked by high INHBA and FAP coexpression. Single-cell comparisons between patient-derived organoids (PDO) and primary tumors highlighted inter- and intralineage similarities and differences, demarcating molecular boundaries of PDOs as experimental models. We complemented these findings by spatial transcriptomics, orthogonal validation in independent bulk RNA-sequencing cohorts, and functional demonstration using in vitro and in vivo models. Our results provide a high-resolution molecular resource of intra- and interpatient lineage states across distinct gastric cancer subtypes.Significance:We profiled gastric malignancies at single-cell resolution and identified increased plasma cell proportions as a novel feature of diffuse-type tumors. We also uncovered distinct cancer-associated fibroblast subtypes with INHBA–FAP-high cell populations as predictors of poor clinical prognosis. Our findings highlight potential origins of deregulated cell states in the gastric tumor ecosystem.This article is highlighted in the In This Issue feature, p. 587

Supplementary Data from Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric Cancer

This study mainly is carried out to discuss the effect of nitrogen annealing temperature on perovskite solar cells. The annealing temperature affects perovskite solar cells during the annealing process. It also affects the formation of perovskite crystals. Perovskite crystals need to form in a nitrogen box for manufacturing Perovskite solar cells. Spin-coating MAPbI3 on the substrate is annealed with a nitrogen furnace tube to form perovskite crystals. The remaining PbI2 after the annealing is completed to improve the efficiency of perovskite solar cells. The optimal temperature for the formation of perovskite crystals is found by adjusting the annealing temperature. By using UV-visible spectrometer, field emission-scanning electron microscope, and measurements of photoelectric conversion efficiency, cell structure and optoelectronic properties are analyzed as the final results.

Gastric cancer heterogeneity represents a barrier to disease management. We generated a comprehensive single-cell atlas of gastric cancer (>200,000 cells) comprising 48 samples from 31 patients across clinical stages and histologic subtypes. We identified 34 distinct cell-lineage states including novel rare cell populations. Many lineage states exhibited distinct cancer-associated expression profiles, individually contributing to a combined tumor-wide molecular collage. We observed increased plasma cell proportions in diffuse-type tumors associated with epithelial-resident KLF2 and stage-wise accrual of cancer-associated fibroblast subpopulations marked by high INHBA and FAP coexpression. Single-cell comparisons between patient-derived organoids (PDO) and primary tumors highlighted inter- and intralineage similarities and differences, demarcating molecular boundaries of PDOs as experimental models. We complemented these findings by spatial transcriptomics, orthogonal validation in independent bulk RNA-sequencing cohorts, and functional demonstration using in vitro and in vivo models. Our results provide a high-resolution molecular resource of intra- and interpatient lineage states across distinct gastric cancer subtypes. Significance: We profiled gastric malignancies at single-cell resolution and identified increased plasma cell proportions as a novel feature of diffuse-type tumors. We also uncovered distinct cancer-associated fibroblast subtypes with INHBA–FAP-high cell populations as predictors of poor clinical prognosis. Our findings highlight potential origins of deregulated cell states in the gastric tumor ecosystem. This article is highlighted in the In This Issue feature, p. 587

Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia and the main cause of treatment failure is metastasis. A lot of biological and pharmacological actions of dihydromyricetin (DHM) have been reported such as regulating glucose and anti-cancer effects. The effects of DHM on the cancer invasion and migration of NPC, however, are still unclear. We therefore investigated the in vitro anti-metastatic properties of DHM on three human NPC cell lines (HONE-1, NPC-39, and NPC-BM), as well as the underlying signaling pathways. Our study revealed that DHM could suppress the migration and invasion in NPC cells. Gelatin zymography assay and western blotting assays demonstrated that DHM suppressed the enzyme activity and protein expression of matrix metalloproteinases-2 (MMP-2). Mitogen-activated protein kinases were also investigated to elucidate the signaling pathway, which showed that phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) was inhibited after the treatment of DHM. In conclusion, our data revealed that DHM inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 via down regulating the ERK1/2 signaling pathway.

Direct epitaxial integration of magnetic layers with wide bandgap nitride semiconductors will enable spin-controlled transport and photonic phenomena, seeding ideas for functional spintronic devices. Using plasma-assisted molecular beam epitaxy (MBE) in a previously unexplored window, significantly improved ferrimagnetic Mn4N layers are successfully grown on GaN with ~ 1 nm surface roughness. Distinct from earlier reports, the Mn4N layers grown on GaN are found to be 001 oriented with 12-fold in-plane symmetry in the diffraction pattern. This unique epitaxial registry originates from three equivalent rotational domains. The ferrimagnetic magnetotransport properties of low growth temperature Mn4N layers on GaN are comparable to those reported on cubic substrates such as MgO. However, a sign-flip of the Hall resistance is discovered for Mn4N layers grown above 300 °C.

Clostridioides difficile infection (CDI) is a common cause of nosocomial diarrhea. TcdB is a major C. difficile exotoxin that activates macrophages to promote inflammation and epithelial damage. Lysosome impairment is a known trigger for inflammation. Herein, we hypothesize that TcdB could impair macrophage lysosomal function to mediate inflammation during CDI. Effects of TcdB on lysosomal function and the downstream pro-inflammatory SQSTM1/p62-NFKB (nuclear factor kappa B) signaling were assessed in cultured macrophages and in a murine CDI model. Protective effects of two lysosome activators (i.e., vitamin D3 and carbamazepine) were assessed. Results showed that TcdB inhibited CTNNB1/β-catenin activity to downregulate MITF (melanocyte inducing transcription factor) and its direct target genes encoding components of lysosomal membrane vacuolar-type ATPase, thereby suppressing lysosome acidification in macrophages. The resulting lysosomal dysfunction then impaired autophagic flux and activated SQSTM1-NFKB signaling to drive the expression of IL1B/IL-1β (interleukin 1 beta), IL8 and CXCL2 (chemokine (C-X-C motif) ligand 2). Restoring MITF function by enforced MITF expression or restoring lysosome acidification with 1α,25-dihydroxyvitamin D3 or carbamazepine suppressed pro-inflammatory cytokine expression in vitro. In mice, gavage with TcdB-hyperproducing C. difficile or injection of TcdB into ligated colon segments caused prominent MITF downregulation in macrophages. Vitamin D3 and carbamazepine lessened TcdB-induced lysosomal dysfunction, inflammation and histological damage. In conclusion, TcdB inhibits the CTNNB1-MITF axis to suppress lysosome acidification and activates the downstream SQSTM1-NFKB signaling in macrophages during CDI. Vitamin D3 and carbamazepine protect against CDI by restoring MITF expression and lysosomal function in mice. Abbreviations: ATP6V0B: ATPase H+ transporting V0 subunit b; ATP6V0C: ATPase H+ transporting V0 subunit c; ATP6V0E1: ATPase H+ transporting V0 subunit e1; ATP6V1H: ATPase H+ transporting V1 subunit H; CBZ: carbamazepine; CDI: C. difficile infection; CXCL: chemokine C-X-X motif ligand; IL: interleukin; LAMP1: lysosomal-associated membrane protein 1; LC3: microtubule-associated protein 1 light chain 3; LEF: lymphoid enhancer binding factor 1; MITF: melanocyte inducing transcription factor; NFKB: nuclear factor kappa B; PMA: phorbol 12-myristate 13-acetate; TcdA: Clostridial toxin A; TcdB: Clostridial toxin B; TFE3: transcription factor E3; TFEB: transcription factor EB. Published version This work was supported by the National Natural Science Foundation of China [82070576] and the Hong Kong Food and Health Bureau (FHB) Commissioned Health and Medical Research Fund [CID-CUHK-C].

To counteract proteotoxic stress and cellular aging, protein quality control (PQC) systems rely on the refolding, degradation and sequestration of misfolded proteins. In Saccharomyces cerevisiae the Hsp70 chaperone system plays a central role in protein refolding, while degradation is predominantly executed by the ubiquitin proteasome system (UPS). The sequestrases Hsp42 and Btn2 deposit misfolded proteins in cytosolic and nuclear inclusions, thereby restricting the accessibility of misfolded proteins to Hsp70 and preventing the exhaustion of limited Hsp70 resources. Therefore, in yeast, sequestrase mutants show negative genetic interactions with double mutants lacking the Hsp70 co-chaperone Fes1 and the Hsp104 disaggregase (fes1Δ hsp104Δ, ΔΔ) and suffering from low Hsp70 capacity. Growth of ΔΔbtn2Δ mutants is highly temperature-sensitive and results in proteostasis breakdown at non-permissive temperatures. Here, we probed for the role of the ubiquitin proteasome system in maintaining protein homeostasis in ΔΔbtn2Δ cells, which are affected in two major protein quality control branches. We show that ΔΔbtn2Δ cells induce expression of diverse stress-related pathways including the ubiquitin proteasome system to counteract the proteostasis defects. Ubiquitin proteasome system dependent degradation of the stringent Hsp70 substrate firefly Luciferase in the mutant cells mirrors such compensatory activities of the protein quality control system. Surprisingly however, the enhanced ubiquitin proteasome system activity does not improve but aggravates the growth defects of ΔΔbtn2Δ cells. Reducing ubiquitin proteasome system activity in the mutant by lowering the levels of functional 26S proteasomes improved growth, increased refolding yield of the Luciferase reporter and attenuated global stress responses. Our findings indicate that an imbalance between Hsp70-dependent refolding, sequestration and ubiquitin proteasome system-mediated degradation activities strongly affects protein homeostasis of Hsp70 capacity mutants and contributes to their severe growth phenotypes.

Genu valgum results in lower limb malalignment and altered joint mechanics. The study aimed to identify the effects of genu valgum on balance control and muscular work at the joints during gait in children.Would bilateral genu valgum affect balance control and muscular work at the joints during gait in children?Thirteen children with genu valgum and thirteen healthy peers walked at their preferred speed while the body's motions and ground reaction forces were measured to calculate the inclination angles (IA) and the rates of change of IA (RCIA) of the body's center of mass (COM) relative to the center of pressure (COP), as well as the muscular work done at the joints. An independent t-test was used to compare the variables between groups (α = 0.05).Compared to the controls, the patients showed significantly increased step width with altered frontal IA and RCIA variables (p0.05), including increased average IA over single-limb support and increased peak RCIA during double-limb support (p0.05). The patients significantly increased posterior RCIA at heel-strike but decreased anterior RCIA at toe-off (p0.05). The patients showed increased muscular work at both the hip and knee during single-limb support (p0.05).The children with genu valgum showed a specific balance control strategy during gait. In the frontal plane, greater hip and knee muscular work was needed to maintain balance under an increased IA, likely owing to increased step width associated with the valgus alignment. In the sagittal plane, less smooth and less stable COM-COP control with increased RCIA at the key gait events indicates faster weight transfer between double-limb and single-limb support. It is suggested that patients with genu valgum, especially in more severe cases, should be monitored for signs of decreased ability and/or muscular strength in maintaining balance during gait.

Online Appendix

The effect of varying amounts of CoAl2O4 inoculant ranging from 0 to 2 wt pct on the microstructure evolution of Inconel 718(IN718) fabricated by selective laser melting (SLM) was evaluated. Characterization of the as-built microstructure revealed that addition of CoAl2O4 resulted in a modest degree of grain refinement with a slight increase in microstructural anisotropy. Increasing the total CoAl2O4 content beyond 0.2 wt pct resulted in severe agglomeration of the non-metallic particles and the formation of slag inclusions measuring up to 100 μm in size present in the as-built microstructure. In addition to large agglomerates, the inoculant was chemically reduced to form a fine dispersion of submicron-sized Al2O3 particles throughout the IN718 matrix. The fine dispersion of oxides significantly hindered grain recrystallization during the post-fabrication heat treatment due to a Zener pinning effect. The findings from this study indicate in order to effectively utilize CoAl2O4 as a grain refining inoculant for additive manufacturing, the process parameters need to be optimized to avoid agglomeration of the non-metallic particles and other process-related defects.

The component of working memory that the frontal cortex subserves is frequently characterized as the executive working memory (EWM). This study applied a neuropsychological measure of EWM (NPM-EWM) in older adults with memory impairment to investigate the EWM. Thirty-two older adults from the community were recruited as older healthy controls (OHCs), and 58 older adults from a memory clinic were diagnosed with mild cognitive impairment (MCI) and mild dementia (MD). Significant differences were found among the three groups in the Clinical Dementia Rating (CDR), the Chinese version of Mini-Mental State Examination (MMSE-C), and the Cognitive Abilities Screening Instrument (CASI). The NPM-EWM was applied by using the learning task of the Comprehensive Nonverbal Memory Test Battery, where the 7 scores were divided into two categories: mnemonic capacity and executive error. All OHCs, more than 50% MCI, and less than 25% of MD patients passed the NPM-EWM. The MCI-passed and MD-passed subgroups showed similar mnemonic capacity and executive errors, and both the subgroups had significantly worse performance than the OHC group. The MD-passed subgroup had a higher Hamilton Depression Rating Scale (HDRS) score than did the MD-failed subgroup. The MCI-failed subgroup had a higher Hierarchy of Care Required (HCR) level in instrumental activities of daily living (IADL) than did the MCI-passed subgroup. These findings indicated that applying the NPM-EWM for older adults with memory impairment may offer precise and tailored care to a whole person, especially for the MCI patients with poorer EWM and the MD patients with relatively intact EWM.

This study presents a technique for measuring the centering error of a lens. The technique uses power analysis and is highly accurate. The module is designed by a prism that is patterned using a subwavelength grating combined with a reflection-centering system by using the −1st-order rays at 5 mW and 650 nm. The optical axis error is tested and analyzed by the powermeter by using Snell’s law and diffractive characteristics. The resolution of the optical-centering error in the system is amplified by a factor of 4 compared with the centering error measuring system based on autocollimation. The technique proposed in this study improves the sensitivity of the instrument and reduces the requirements of the sensor at the end side based on the direction or energy variation of the light.

Silicon carbide (SiC) is a typical, difficult-to-machine material that has been widely used in the fabrication of optical elements and structural and heat-resistant materials. Parallel grinding has been frequently adopted to produce a high-quality surface finish. Surface generation is a vital issue for assessing surface quality, and extensive modeling has been developed. However, most of the models were based on a disc wheel with a cylindrical surface, whereas the surface topography generation based on an arc-shaped tool has been paid relatively little attention. In this study, a new theoretical model for surface generation in ultra-precision parallel grinding has been established by considering the arc-shaped effect, synchronous vibration of the wheel, and cutting profile interference in the tool feed direction. Finally, the ground surface generation mechanism and grinding ductility were analyzed in the grinding of SiC ceramics. The results showed that the spiral and straight-line mode vibration patterns were the main feature of the machined surface, and its continuity was mainly affected by the phase shift. Furthermore, for the in-phase shift condition, the grinding ductility was more significant than for the out-of-phase shift due to the continuously decreasing relative linear speed between the wheel and workpiece.

Optical fiber gratings inscribed on polymer fibers are more versatile compare with those in silica fibers due to the diversity of the polymers. However the present polymer fiber gratings have weak thermostability as they are made on thermoplastic materials. In this work, we have greatly improved their thermostability by developing a novel fiber grating on thermosetting silicone using deep ultraviolet (UV) laser induced refractive index (RI) increment and ablation. The spectra evolutions in high temperatures thermal treatment have been recorded in order to demonstrate the thermal stability. Nano silica particles dopant owing to the high wettability of silicone could further stabilize the grating. The Raman spectra show partial pyrolysis reactions of the silicone grating at high temperature, and the basis for stability.

Growing concerns about "online harm" and "duty of care" fuel debate about how best to regulate and moderate "troubling content" on social media. This has become a pressing issue in relation to the potential application of media guidelines to online discussion of death by suicide-discussion which is troubling because it is often transgressive and contested. Drawing on an innovative mixed-method analysis of a large-scale Twitter dataset, this article explores in depth, for the first time, the complexities of applying existing media guidelines on reporting death by suicide to online contexts. By focusing on five highly publicised deaths, it illustrates the limits of this translation but also the significance of empathy (its presence and absence) in online accounts of these deaths. The multi-relational and politicised nature of empathy, and the polarised nature of Twitter debate, suggests that we need to step back from calls for the automatic application of guidelines produced in a pre-digital time to understand more about the sociocultural context of how suicide is discussed on social media. This stepping back matters because social media is now a key part of how lives and deaths are deemed grievable and deserving of our attention.

Prior literature has debated over whether the age-related positivity effect, defined as older adults showing a greater bias in cognitive processing for positively over negatively valenced information relative to younger adults, is goal-driven. This study attempted to directly address this debate by disentangling the influences of valence alone and the instrumentality of emotion on visual attention toward valenced stimuli. We reasoned that if the age-related positivity effect was goal-driven, it would be reversed, that is, older adults would pay more attention to anger-related than happiness-related stimuli when anger was made instrumental for the context. Eye-tracking findings generally support this hypothesis, suggesting that as we age, we selectively prioritize stimuli that are useful to us, not necessarily pleasant stimuli, in cognitive processing. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Purpose An objective and quantitative assessment of facial symmetry is essential for the surgical planning and evaluation of treatment outcomes in orthognathic surgery (OGS). This study applied the transfer learning model with a convolutional neural network based on 3-dimensional (3D) contour line features to evaluate the facial symmetry before and after OGS. Methods A total of 158 patients were recruited in a retrospective cohort study for the assessment and comparison of facial symmetry before and after OGS from January 2018 to March 2020. Three-dimensional facial photographs were captured by the 3dMD face system in a natural head position, with eyes looking forward, relaxed facial muscles, and habitual dental occlusion before and at least 6 months after surgery. Three-dimensional contour images were extracted from 3D facial images for the subsequent Web-based automatic assessment of facial symmetry by using the transfer learning with a convolutional neural network model. Results The mean score of postoperative facial symmetry showed significant improvements from 2.74 to 3.52, and the improvement degree of facial symmetry (in percentage) after surgery was 21% using the constructed machine learning model. A Web-based system provided a user-friendly interface and quick assessment results for clinicians and was an effective doctor-patient communication tool. Conclusions This work was the first attempt to automatically assess the facial symmetry before and after surgery in an objective and quantitative value by using a machine learning model based on the 3D contour feature map.