A population-based study exploring association of parasomnia symptoms with sleep onset delay among school-aged children.

OBJECTIVE: Parasomnia is potentially implicated in sleep pattern and sleep architecture, however, evidence is quite limited. This study aimed to investigate the association between parasomnia symptoms and sleep onset delay among children through a large epidemiological study. METHODS: Two rounds of cross-sectional studies were conducted among 21,704 children aged 3-11; one taking place in Shanghai and the other in Sanya, Hainan province. Children's sleep characteristics were evaluated using the Children's Sleep Habits Questionnaire (CSHQ). Propensity score matching was adopted to balance the difference of covariates, and the logistic regression models were implemented to examine the associations between parasomnia symptoms and sleep onset delay. RESULTS: A total of 38.2 % of children had sleep onset delay. Parasomnias, especially non rapid eye movement (NREM) and rapid eye movement (REM) parasomnia symptoms, were associated with an increased risk of sleep onset delay (Sleep Walking: OR = 1.55; Sleep Terror: OR = 1.34; Nightmare: OR = 1.37, all p˂0.001). The similar findings were observed in stratified analyses according to sleep duration, and the association was pronounced in sleep sufficiency group (Sleep Walking: OR = 1.62; Sleep Terror: OR = 1.35; Nightmare: OR = 1.35, all p˂0.001). Moreover, a dose-dependent pattern was observed, in which cumulative parasomnia symptoms were associated with increasing risk of sleep onset delay (2 symptoms: OR = 1.19; ≥3 symptoms: OR = 1.40; by comparison with ≤1 symptom). All these findings were also similarly observed in the propensity score matching sample. Moreover, the associations were generally established in both Shanghai and Sanya children. CONCLUSIONS: Parasomnia symptoms were associated with a higher risk of sleep onset delay independently of sleep duration among children. More studies are needed to enrich the current evidence, thus further clarifying the association and interaction among different sleep parameters.

Free time-induced retroactive effects in working memory: Evidence from the single-gap paradigm.

Free time in a working memory task often improves the recall performances of the to-be-remembered items. It is still debated whether the free-time effect in working memory is purely proactive, purely retroactive, or both proactive and retroactive. In the present study, we used the single-gap paradigm to explore this question. In Experiment 1, we measured the gap-length effect (i.e., the difference in memory performance elicited by the gap-length difference) under three long-short-gap combinations (i.e., 2,500 ms/100 ms, 2,500 ms/500 ms, 2,500 ms/1,000 ms). Proactive effects have been observed in all the three combinations whereas retroactive effects have only been found in two of them (i.e., 2,500 ms/100 ms, 2,500 ms/500 ms). To rule out the possibility that the retroactive effects found in Experiment 1 were simply due to the temporal grouping caused by the gap, in Experiment 2, the 2,500 ms/500 ms combination was retested, with the memory materials being changed from letters (the material used in Experiment 1) to words. The results showed that the range of the retroactive effect (i.e., the number of affected memory items prior to the gap) increased when the memory material changed from letters to words, which cannot be explained by temporal grouping. Taken together, the two experiments provided solid evidence that free time in working memory could produce both retroactive and proactive effects that cannot be explained by temporal grouping. These findings also provide insight into the underlying mechanism of working memory, for example, whether rehearsal would occur during the free time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Composite Microfluidic Petri Dish-Chip (MPD-Chip) without Protein Coating for 2D Cell Culture.

Hydrophilicity is a requisite attribute for the 2D cell culture substrate's surface, facilitating cell adhesion and spreading. Conventional poly(dimethylsiloxane) (PDMS) microfluidic chips necessitate protein coatings to enhance hydrophilicity; however, this approach is afflicted by issues of transient efficacy, interference with cell analysis, and high costs. This paper presents a protein-free microfluidic chip, termed a "microfluidic Petri dish-chip (MPD-chip)", integrating PDMS as the cover and a tissue culture-treated (TC-treated) Petri dish as the substrate. Microstructures are hot-embossed onto the Petri dish substrate using a silicon mold. This meticulous replication process serves to establish stable flow field dynamics within the chip. A simplified method for irreversible bonding, utilizing plasma activation and silylation, is proposed for affixing the PDMS cover onto the microstructured Petri dish substrate. The prepared composite chip exhibits remarkable tightness, boasting a notable bond strength of 2825 kPa. Furthermore, the composite microfluidic chip demonstrates the capability to withstand flow velocities of at least 200 µL/min, effectively meeting the required injection standards for both cell suspension and culture medium. SH-SY5Y and HeLa cells are cultured dynamically in the MPD-chip and control groups. Outcomes encompassing normalized cell density, cell adhesion area, and cell viability metrics unequivocally highlight the superiority of the MPD-chip in facilitating long-term two-dimensional (2D) cell cultures.

Cost-effectiveness of neoadjuvant pembrolizumab plus chemotherapy with adjuvant pembrolizumab for early-stage non-small cell lung cancer in the United States.

Introduction: Perioperative (neoadjuvant and adjuvant) pembrolizumab has shown favorable efficacy in patients with early-stage non-small cell lung cancer (NSCLC). This study aims to evaluate the cost-effectiveness of this treatment from the perspective of the United States healthcare payers. Methods: We established a Markov model to compare the cost-effectiveness of perioperative pembrolizumab with that of neoadjuvant chemotherapy in 21-day cycles, utilizing data from the phase 3 KEYNOTE-671 trial. Additional data were extracted from other publications or online sources. Sensitivity analyses were conducted to evaluate the robustness of the findings. A willingness-to-pay threshold of $150,000 per quality-adjusted life-years (QALYs) gained was established. The main outcomes of this study were the measurement of QALYs, overall costs, incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB). Results: During a 10-year time horizon, the total costs of perioperative pembrolizumab and the control treatment were $224,779.1 and $110,026.3, respectively. The QALYs were 4.19 and 2.97 for the two treatments, respectively, which led to an ICER of $94,222.29 per QALY gained. The NMB at the WTP threshold at $150,000 per QALY gained was $67,931.3. One-way sensitivity analysis identified the cost of pembrolizumab as the primary factor influencing cost-effectiveness. Probabilistic sensitivity analysis indicated a 97.7% probability of perioperative pembrolizumab being cost-effective at the WTP threshold. Conclusions: From the perspective of the United States healthcare payers, perioperative pembrolizumab is a cost-effective treatment for patients with early-stage NSCLC.

Assessing causal relationships between gut microbiota and asthma: evidence from two sample Mendelian randomization analysis.

Background: Accumulating evidence has suggested that gut microbiota dysbiosis is commonly observed in asthmatics. However, it remains unclear whether dysbiosis is a cause or consequence of asthma. We aimed to examine the genetic causal relationships of gut microbiota with asthma and its three phenotypes, including adult-onset asthma, childhood-onset asthma, and moderate-severe asthma. Methods: To elucidate the causality of gut microbiota with asthma, we applied two sample Mendelian randomization (MR) based on the largest publicly available genome-wide association study (GWAS) summary statistics. Inverse variance weighting meta-analysis (IVW) was used to obtain the main estimates; and Weighted median, MR-Egger, Robust Adjusted Profile Score (MR-RAPS), Maximum likelihood method (ML), and MR pleiotropy residual sum and outlier (MR-PRESSO) methods were applied in sensitivity analyses. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation. Results: In the absence of heterogeneity and horizontal pleiotropy, the IVW method revealed that genetically predicted Barnesiella and RuminococcaceaeUCG014 were positively correlated with the risk of asthma, while the association between genetically predicted CandidatusSoleaferrea and asthma was negative. And for the three phenotypes of asthma, genetically predicted Akkermansia reduced the risk of adult-onset asthma, Collinsella and RuminococcaceaeUCG014 increased the risk of childhood-onset asthma, and FamilyXIIIAD3011group, Eisenbergiella, and Ruminiclostridium6 were correlated with the risk of moderate-severe asthma (all P<0.05). The reverse MR analysis didn't find evidence supporting the reverse causality from asthma and its three phenotypes to the gut microbiota genus. Conclusion: This study suggested that microbial genera were causally associated with asthma as well as its three phenotypes. The findings deepened our understanding of the role of gut microbiota in the pathology of asthma, which emphasizes the potential of opening up a new vista for the prevention and diagnosis of asthma.

Association of residential greenness with chronotype among children.

BACKGROUND: The association between residential greenness and chronotype remains unclear, especially among children. The current study aimed to explore the associations between residential greenness and chronotype parameters in children and examine potential pathways for these associations. METHODS: In this cross-sectional study, 16,421 children ages 3-12 were included. Two satellite-derived vegetation indices, i.e., the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI), were used to estimate residential greenness. The mid-sleep point on a workday (MSW) and the mid-sleep point on free days (MSF) were considered. And mid-sleep time on free days adjusted for sleep debt (MSFsc) was used as an indicator of chronotype. In addition to multivariable linear regression models, subgroup analyses were conducted to explore effect modifiers, and mediation analyses were used to explore possible mediating mechanisms of air pollutants underlying the associations. RESULTS: An interquartile range (IQR) increase in both NDVI500-m and EVI500-m was significantly associated with an earlier MSFsc of -0.061 (95 % confidence interval (CI): -0.072, -0.049) and -0.054 (95 % CI: -0.066, -0.042), respectively. Non-linear dose response relationships were discovered between greenness indices and MSFsc and MSF. The results of stratified analyses showed the effect of residential greenness on MSW was stronger among primary school children and individuals with higher household income than among kindergarten children and those with lower household income. The joint mediation effects of PM2.5, PM1, PM10, NO2, and SO2 on the associations of NDVI500-m and EVI500-m with MSFsc were 89.6 % and 76.0 %, respectively. CONCLUSIONS: Higher levels of residential greenness may have beneficial effects on an earlier chronotype in the child population, by reducing the effects of air pollutants, especially PM2.5. Our research hopes to promote the deployment of green infrastructure and healthy urban design strategies.

A cell-electrode interface signal-to-noise ratio model for 3D micro-nano electrode.

Objective. Three-dimensional micro-nano electrodes (MNEs) with the vertical nanopillar array distributed on the surface play an increasingly important role in neural science research. The geometric parameters of the nanopillar array and the cell adhesion state on the nanopillar array are the factors that may affect the MNE recording. However, the quantified relationship between these parameters and the signal-to-noise ratio (SNR) is still unclear. This paper establishes a cell-MNE interface SNR model and obtains the mathematical relationship between the above parameters and SNR.Approach. The equivalent electrical circuit and numerical simulation are used to study the sensing performance of the cell-electrode interface. The adhesion state of cells on MNE is quantified as engulfment percentage, and an equivalent cleft width is proposed to describe the signal loss caused by clefts between the cell membrane and the electrode surface.Main results. Whether the planar substrate is insulated or not, the SNR of MNE is greater than planar microelectrode only when the engulfment percentage is greater than a certain value. Under the premise of maximum engulfment percentage, the spacing and height of nanopillars should be minimized, and the radius of the nanopillar should be maximized for better signal quality.Significance. The model can clarify the mechanism of improving SNR by nanopillar arrays and provides the theoretical basis for the design of such nanopillar neural electrodes.

Identification of Inflammatory Endotypes by Clinical Characteristics and Nasal Secretion Biomarkers in Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: The emergency of biologics and surgical techniques targeting the specific inflammatory endotype in chronic rhinosinusitis with nasal polyps (CRSwNP) asks for efficient identification of patients with different endotypes. Although mucosal IL-4, IL-5, IL-13, and IgE have been used to define type 2 (T2) inflammation, the optimal one remains unclear. In this study, we aimed to determine the optimal anchor for T2 inflammation and identify clinical characteristics and nasal secretion biomarkers predicting different endotypes in CRSwNP. METHODS: Six mediators in sinonasal tissue and 36 mediators in nasal secretion samples were detected by the Bio-Plex suspension array system. Mucosal IFN-γ and IL-17A levels were used to define the T1 and T3 endotype, respectively. The efficacy of mucosal IL-4, IL-5, IL-13, and IgE to define the T2 endotype was compared. The power of clinical characteristics and nasal secretion biomarkers to predict the T1, T2, and T3 endotype was analyzed. RESULTS: Among mucosal IL-4, IL-5, IL-13, and IgE, IL-13 was the best one to coincide with the expression of other T2 biomarkers. A combination of atopy, facial pain symptom score, ethmoid/maxillary computed tomography score ratio, and blood eosinophil percentage had a moderate predictive performance for T2 endotype (area under the receiver operating curve [AUC] = 0.815), comparable to that of nasal secretion IL-5 (AUC = 0.819). For the T3 endotype, nasal secretion IL-1Rα identified it with an AUC value of 0.756. No efficient marker for the T1 endotype was found. CONCLUSION: IL-13 is a primary anchor for the T2 endotype in CRSwNP. Clinical characteristics and nasal secretion biomarkers are helpful for identifying the T2 and T3 endotype of CRSwNP.

Perturbated glucose metabolism augments epithelial cell proinflammatory function in chronic rhinosinusitis.

BACKGROUND: Glucose concentrations are increased in nasal secretions in chronic rhinosinusitis (CRS). However, the glucose metabolism and its contribution to disease pathogenesis in CRS remain unexplored. OBJECTIVES: We sought to explore the glucose metabolism and its effect on the function of nasal epithelial cells in CRS with and without nasal polyps (CRSwNP and CRSsNP). METHODS: Glucose metabolites were detected with mass spectrometry. The mRNA levels of glucose transporters (GLUTs), metabolic enzymes, and inflammatory mediators were detected by quantitative RT-PCR. The protein expression of GLUTs was studied by immunofluorescence staining, Western blotting, and flow cytometry. Glucose uptake was measured by using fluorescent glucose analog. Human nasal epithelial cells (HNECs) were cultured. Bioenergetic analysis was performed with Seahorse XF analyzer. Gene expression in HNECs was profiled by RNA sequencing. RESULTS: Increased glucose concentrations in nasal secretions was confirmed in both CRSsNP and CRSwNP. GLUT4, GLUT10, and GLUT11 were abundantly expressed in HNECs, whose expression was upregulated by inflammatory cytokines and D-glucose and was increased in CRS. Glucose uptake, glycolysis and tricarboxylic acid cycle metabolites, metabolic enzymes, and extracellular acidification rate and oxygen consumption rates were increased in HNECs in CRSsNP and CRSwNP, with a predominant shift to glycolysis. HNECs treated with high-level apical D-glucose showed enhanced glucose uptake, predominant glycolysis, and upregulated production of IL-1α, IL-1ß, TNF-α, CCL20, and CXCL8, which was suppressed by 2-deoxy-D-glucose, an inhibitor of glycolysis. CONCLUSIONS: Increased glucose in nasal secretions promotes glucose uptake and predominant glycolysis in epithelial cells, augmenting the proinflammatory function of epithelial cells in CRS.

A microfluidic device inspired by leaky tumor vessels for hematogenous metastasis mechanism research.

Endothelial intercellular pores of tumor vessels generally lead to enhanced interstitial flow and may facilitate the migration of tumor cells. The permeability of tumor vessels causes a concentration gradient of growth factors (CGGF) from blood vessels to tumor tissues, which is opposite to the direction of interstitial flow. In this work, exogenous chemotaxis under the CGGF is demonstrated as a mechanism of hematogenous metastasis. A bionic microfluidic device inspired by endothelial intercellular pores of tumor vessels has been designed to study the mechanism. A porous membrane vertically integrated into the device using a novel compound mold is utilized to mimic the leaky vascular wall. The formation mechanism of the CGGF caused by endothelial intercellular pores is numerically analyzed and experimentally verified. The migration behavior of U-2OS cells is studied in the microfluidic device. The device is divided into three regions of interest (ROI): primary site, migration zone, and tumor vessel. The number of cells in the migration zone increases significantly under the CGGF, but decreases under no CGGF, indicating tumor cells may be guided to the vascellum by exogenous chemotaxis. Transendothelial migration is subsequently monitored, demonstrating the successful replication of the key steps in vitro in the metastatic cascade by the bionic microfluidic device.

Strategic orientation, business model innovation and corporate performance-Evidence from construction industry.

In the highly competitive Chinese construction market, developing a strategic orientation alone fails to maintain the sustainable competitive advantage of firms. In this paper, the mechanism of strategic orientation and business model innovation on corporate performance in a dynamic environment is investigated. Based on a sample of 356 Chinese construction firms, the partial least squares structural equation modelling (PLS-SEM) was adopted to test the hypotheses. It is found that entrepreneurial orientation and market orientation affect corporate performance differently. Unlike market orientation, which directly affects corporate performance, entrepreneurial orientation through business model innovation exerts influence instead of direct affection. Business model innovation plays a fully mediating role between entrepreneurial orientation and corporate performance and partially between market orientation and corporate performance. Meanwhile, environmental dynamism can positively moderate the relationship between business model innovation and corporate performance. This paper deepens the research on strategic orientation, business model innovation and corporate performance. The findings can provide a reference for construction firm managers to develop strategies and conduct business model innovation, which can finally help seek sustainable development in a dynamic environment.

Metagenomics next-generation sequencing for the diagnosis of central nervous system infection: A systematic review and meta-analysis.

Objective: It is widely acknowledged that central nervous system (CNS) infection is a serious infectious disease accompanied by various complications. However, the accuracy of current detection methods is limited, leading to delayed diagnosis and treatment. In recent years, metagenomic next-generation sequencing (mNGS) has been increasingly adopted to improve the diagnostic yield. The present study sought to evaluate the value of mNGS in CNS infection diagnosis. Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2022 guidelines, we searched relevant articles published in seven databases, including PubMed, Web of Science, and Cochrane Library, published from January 2014 to January 2022. High-quality articles related to mNGS applications in the CNS infection diagnosis were included. The comparison between mNGS and the gold standard of CNS infection, such as culture, PCR or serology, and microscopy, was conducted to obtain true positive (TP), true negative (TN), false positive (FP), and false negative (FN) values, which were extracted for sensitivity and specificity calculation. Results: A total of 272 related studies were retrieved and strictly selected according to the inclusion and exclusion criteria. Finally, 12 studies were included for meta-analysis and the pooled sensitivity was 77% (95% CI: 70-82%, I 2 = 39.69%) and specificity was 96% (95% CI: 93-98%, I 2 = 72.07%). Although no significant heterogeneity in sensitivity was observed, a sub-group analysis was conducted based on the pathogen, region, age, and sample pretreatment method to ascertain potential confounders. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for CNS infection was 0.91 (95% CI: 0.88-0.93). Besides, Deek's Funnel Plot Asymmetry Test indicated no publication bias in the included studies (Figure 3, p > 0.05). Conclusion: Overall, mNGS exhibits good sensitivity and specificity for diagnosing CNS infection and diagnostic performance during clinical application by assisting in identifying the pathogen. However, the efficacy remains inconsistent, warranting subsequent studies for further performance improvement during its clinical application. Study registration number: INPLASY202120002.

The Impact of Scenarios on the Performance of Entrepreneurial Imaginativeness: Evidence From an Experiment.

With the advent of the era of artificial intelligence, "scenario" frequently appears in new product development and has gradually become an effective tool for analyzing user needs. However, the reasons for this phenomenon have not been explored in depth. New product development is a creative activity that requires product designers to imagine how people will live in the near future. So, we speculated that a familiar scenario that matches designers' background (including knowledge, expertise, and experience) can spark their entrepreneurial imaginativeness by empathic simulation and conducted an experiment to research the impact of scenarios on the performance of entrepreneurial imaginativeness. Results of this study confirmed that a familiar scenario did indeed inspire entrepreneurial imaginativeness more than an unfamiliar scenario, especially for high entrepreneurial imaginativeness. This study provided a new respective for understanding the relationship between the empathy process and entrepreneurial opportunity recognition and evaluation processes and had practical implications for entrepreneurial practice, especially those that make human life better based on new digital technologies. Finally, we gave some suggestions on enhancing individuals' entrepreneurial imaginativeness through different familiar scenarios and improving the team performance on creative tasks.

Set size effects in spatial updating are independent of the online/offline updating strategy.

Spatial updating of self-to-object spatial relations may be performed online or offline. The set size effects in spatial updating are generally considered as a benchmark for indicating which updating strategy is used. Online updating is associated with transient egocentric representations and the presence of set size effects, whereas offline updating is associated with enduring allocentric representations and the absence of set size effects. In the present study, the updating strategy and the available spatial representations in updating were manipulated factorially. In a working memory (WM) paradigm, observers briefly learned a new layout of objects in each trial such that only the transient spatial representation was available during updating, whereas in a reference memory (RM) paradigm, observers learned the same layout of objects across trials such that both transient and enduring representations were available in updating. In both paradigms, observers were instructed to update online or offline. Set size effects showed up only in the WM paradigm but disappeared in the RM paradigm, regardless of the updating strategy. These results suggest that both updating strategies will produce set size effects if they use transient representations alone and that set size effects can be eliminated as long as enduring representations are used. These findings challenge the 2-system theories of spatial updating by showing that although online updating is naturally associated with transient spatial presentations, whereas offline updating is naturally associated with enduring representations, these default associations can be switched under manipulation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).