Compulsivity-related behavioral features of problematic usage of the internet: A scoping review of paradigms, progress, and perspectives.

Background and aims: Compulsivity contributes to the development and maintenance of multiple addictive disorders. However, the relationship between compulsivity-related cognitive features and problematic usage of the internet (PUI), an umbrella term for various internet use disorders/interfering behaviors, remains largely unclear, partly due to the multidimensional nature of compulsivity. This scoping review utilized a four-domain framework of compulsivity to consider this topic and aimed to summarize available evidence on compulsivity-related neuropsychological characteristics in PUI based on this framework. Methods: A systematic literature search was conducted by applying the combination of search term to the search engines of PubMed, PsycINFO and Web of Science. A four-domain framework of compulsivity, involving cognitive flexibility, set-shifting, attentional bias, and habit learning, was used to consider its complex structure and frequently used tasks. Main findings in related PUI studies were summarized based on this framework. Our secondary aim was to compare compulsivity-related features between different PUI subtypes. Results: Thirty-four empirical studies were retained, comprising 41 task-results and 35 independent data sets. Overall, individuals with PUI showed more consistent deficits in attentional biases and were relatively intact in set-shifting. Few studies have examined cognitive flexibility and habit learning, and more evidence is thus needed to establish reliable conclusions. Moreover, most studies focused on internet gaming disorder, whereas other PUI sub-types were not sufficiently examined. Conclusion: This systematic review highlights the use of the four-domain framework for advancing understanding of mechanisms underlying compulsivity in PUI. Related therapeutic implications and future directions are discussed.

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

The Psychosomatic Traits of "People with the Five Elements in Traditional Chinese Medicine": A Qualitative Study.

Objective: To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of "people with the five elements in traditional Chinese medicine (TCM)." Methods: Data collected from the literature review, two sessions of brainstorming of experts with related experience in "people with the five elements in TCM" from October 2020 to December 2020, and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed. Triangulation was used in this study, and theming and synthesizing were used to analyze the data. Results: A total of 31 experts and 30 interviewees participated in this study. The median age of the experts and interviewees were 48.0 and 38.5 years, respectively; 51.66% and 54.8% of experts and interviewees, respectively, were men. The descriptors of facial diagrams of "people with the five elements in TCM" were complexion, shape, distribution state of facial bones, convergence trend of facial muscles, and facial expression. A theoretical model of "people with the five elements in TCM" was shaped based on these findings. Conclusion: The study suggests a possibility for bridging the gap between personality and bodily state, identifying an avenue for personality research from the perspective of TCM.

The dorsomedial prefrontal cortex represents subjective value across effort-based and risky decision-making.

Decisions that require taking effort costs into account are ubiquitous in real life. The neural common currency theory hypothesizes that a particular neural network integrates different costs (e.g., risk) and rewards into a common scale to facilitate value comparison. Although there has been a surge of interest in the computational and neural basis of effort-related value integration, it is still under debate if effort-based decision-making relies on a domain-general valuation network as implicated in the neural common currency theory. Therefore, we comprehensively compared effort-based and risky decision-making using a combination of computational modeling, univariate and multivariate fMRI analyses, and data from two independent studies. We found that effort-based decision-making can be best described by a power discounting model that accounts for both the discounting rate and effort sensitivity. At the neural level, multivariate decoding analyses indicated that the neural patterns of the dorsomedial prefrontal cortex (dmPFC) represented subjective value across different decision-making tasks including either effort or risk costs, although univariate signals were more diverse. These findings suggest that multivariate dmPFC patterns play a critical role in computing subjective value in a task-independent manner and thus extend the scope of the neural common currency theory.

Symptom clusters after chemoradiotherapy in discharged nasopharyngeal carcinoma patients.

Objective: To investigate the incidence of complications and types of chemoradiotherepy induces symptom clusters in patients with nasopharyngeal carcinoma (NPC) who were first diagnosed after treatment and discharged from hospital. Methods: After their discharge home, 130 NPC patients who had been treated with chemoradiotherapy were asked to complete a modified Chinese version of the Quality of Life Questionnaire-Head and Neck Module developed by the European Organization for the Research and Treatment of Cancer in the Head and Neck. Symptom clusters in patients were identified through exploratory factor analysis. Results: The most serious symptoms for discharged NPC patients who had received chemoradiotherapy were dental problems, a sense of obstruction while swallowing, embarrassment in physical contact with family members and friends, difficulty in speaking with others, and embarrassment in public. The six symptom clusters identified through exploratory factor analysis were (1) painful eating, (2) social difficulties, (3) psychological disorders, (4) symptomatic shame, (5) teeth/throat injuries, and (6) sensory abnormalities. The total contribution rate of variance was 65.73%. Conclusion: NPC patients who are treated with chemoradiotherapy can experience adverse symptom clusters that continue after discharge. Nurses should evaluate the patients' symptoms before discharge and provide targeted health education services which would reduce the patients' complications and improve the quality of life at home. Besides, medical staff should evaluate the complications in a timely and comprehensive manner and provide individualized health education for the affected patients to help them manage chemoradiotherapy side effects.

Youth Screen Media Activity Patterns and Associations With Behavioral Developmental Measures and Resting-state Brain Functional Connectivity.

OBJECTIVE: Screen media activity (SMA) consumes considerable time in youth's lives, raising concerns about the effects it may have on youth development. Disentangling mixed associations between SMA of youth and developmental measures should move beyond overall screen time and consider types and patterns of SMA. This study aimed to identify reliable and generalizable SMA patterns among youth and examine their associations with behavioral developmental measures and developing brain functional connectivity. METHOD: Three waves of Adolescent Brain and Cognitive Development (ABCD) data were examined. The Lifespan Human Connectome Project in Development (HCP-D) was interrogated as an independent sample. ABCD participants included 11,876 children at baseline. HCP-D participants included 652 children and adolescents. Youth-reported SMA and behavioral developmental measures (neurocognitive performance, behavioral problems, psychotic-like experiences, impulsivity, and sensitivities to punishment/reward) were assessed with validated instruments. We identified SMA patterns in the ABCD baseline data using K-means clustering and sensitivity analyses. Generalizability and stability of the identified SMA patterns were examined in HCP-D data and ABCD follow-up waves, respectively. Relations between SMA patterns and behavioral and brain (resting-state brain functional connectivity) measures were examined using linear mixed effects modeling with false discovery rate (FDR) correction. RESULTS: SMA data from 11,815 children (mean [SD] age = 119.0 [7.5] months; 6,159 [52.1%] boys) were examined; 3,151 (26.7%) demonstrated a video-centric higher-frequency SMA pattern, and 8,664 (73.3%) demonstrated a lower-frequency pattern. SMA patterns were validated in similarly aged HCP-D youth. Compared with the lower-frequency SMA pattern group, the video-centric higher-frequency SMA pattern group showed poorer neurocognitive performance (ß = -.12, 95% CI [-0.08, -0.16], FDR-corrected p < .001), more total behavioral problems (ß = .13, 95% CI [0.09, 0.18], FDR-corrected p < .001), and more psychotic-like experiences (ß = .31, 95% CI [0.27, 0.36], FDR-corrected p < .001). The video-centric higher-frequency SMA pattern group demonstrated higher impulsivity, more sensitivity to punishment/reward, and altered resting-state brain functional connectivity among brain areas implicated previously in cognitive processes. Most of the associations persisted with age in the ABCD data, with more participants (n = 3,378, 30.4%) in the video-centric higher-frequency SMA group at 1-year follow-up. A social communication-centric SMA pattern was observed in HCP-D adolescents. CONCLUSION: Video-centric SMA patterns are reliable and generalizable during late childhood. A higher-frequency video entertainment SMA pattern group showed altered resting-state brain functional connectivity and poorer developmental measures that persisted longitudinally. The findings suggest that public health strategies to decrease excessive time spent by children on video entertainment-related SMA are needed. Further studies are needed to examine potential video-centric/social communication-centric SMA bifurcation to understand dynamic changes and trajectories of SMA patterns and related outcomes developmentally. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Luteolin alleviated neutrophilic asthma by inhibiting IL-36γ secretion-mediated MAPK pathways.

CONTEXT: Luteolin can affect multiple biological functions, such as anti-inflammatory, antioxidant and immune enhancement processes. Luteolin can inhibit inflammation of T2-high asthma, but its role in neutrophilic asthma has been insufficently studied. OBJECTIVE: This study determines the effect of luteolin on IL-36γ secretion-mediated MAPK pathway signalling in neutrophilic asthma. MATERIALS AND METHODS: The asthma model was established by using ovalbumin/lipopolysaccharide (OVA/LPS). Female 6-8-week-old C57BL/6 mice were divided into control, asthma, luteolin (20 mg/kg) and asthma + luteolin (20 mg/kg) groups. To explore the mechanism of anti-inflammatory effects of luteolin in neutrophilic asthma, Beas-2B cells were treated with luteolin (20 µmol/L), LPS (100 ng/mL), recombinant human IL-36γ protein (rhIL-36γ; 100 ng/mL) or IL-36γ siRNA. RESULTS: IL-36γ secretion and MAPK/IL-1ß signalling were significantly increased in the asthma mouse model compared with the control (p < 0.05). However, the levels of IL-36γ secretion and MAPK/IL-1ß signalling were reduced by luteolin (p < 0.05). In addition, luteolin inhibited IL-36γ and MAPK/IL-1ß levels after LPS (100 ng/mL) stimulation of Beas-2B cells (p < 0.05). We found that in Beas-2B cells, luteolin inhibited activation of the MAPK pathway and IL-1ß secretion following stimulation with rhIL-36γ (100 ng/mL; p < 0.05). Finally, IL-1ß and phosphorylated MAPK levels were found to be lower in the IL-36γ siRNA + LPS (100 ng/mL) group than in the nonspecific control (NC) siRNA + LPS group (p < 0.05). DISCUSSION AND CONCLUSIONS: Luteolin alleviated neutrophilic asthma by inhibiting IL-36γ secretion-mediated MAPK pathways. These findings provided a theoretical basis for the application of luteolin in the treatment of neutrophilic asthma.

Subgroups of internet gaming disorder based on addiction-related resting-state functional connectivity.

AIMS: To identify subgroups of people with internet gaming disorder (IGD) based on addiction-related resting-state functional connectivity and how these subgroups show different clinical correlates and responses to treatment. DESIGN: Secondary analysis of two functional magnetic resonance imaging (fMRI) data sets. SETTING: Zhejiang province and Beijing, China. PARTICIPANTS: One hundred and sixty-nine IGD and 147 control subjects. MEASUREMENTS: k-Means algorithmic and support-vector machine-learning approaches were used to identify subgroups of IGD subjects. These groups were examined with respect to assessments of craving, behavioral activation and inhibition, emotional regulation, cue-reactivity and guessing-related measures. FINDINGS: Two groups of subjects with IGD were identified and defined by distinct patterns of connectivity in brain networks previously implicated in addictions: subgroup 1 ('craving-related subgroup') and subgroup 2 ('mixed psychological subgroup'). Clustering IGD on this basis enabled the development of diagnostic classifiers with high sensitivity and specificity for IGD subgroups in 10-fold validation (n = 218) and out-of-sample replication (n = 98) data sets. Subgroup 1 is characterized by high craving scores, cue-reactivity during fMRI and responsiveness to a craving behavioral intervention therapy. Subgroup 2 is characterized by high craving, behavioral inhibition and activations scores, non-adaptive emotion-regulation strategies and guessing-task fMRI measures. Subgroups 1 and 2 showed largely opposite functional-connectivity patterns in overlapping networks. CONCLUSIONS: There appear to be two subgroups of people with internet gaming disorder, each associated with differing patterns of brain functional connectivity and distinct clinical symptom profiles and gender compositions.

Neural activations to loss anticipation mediates the association between difficulties in emotion regulation and screen media activities among early adolescent youth: A moderating role for depression.

BACKGROUND: Screen media activities (SMAs; e.g., watching videos, playing videogames) have become increasingly prevalent among youth as ways to alleviate or escape from negative emotional states. However, neural mechanisms underlying these processes in youth are incompletely understood. METHOD: Seventy-nine youth aged 11-15 years completed a monetary incentive delay task during fMRI scanning. Neural correlates of reward/loss processing and their associations with SMAs were explored. Next, brain activations during reward/loss processing in regions implicated in the processing of emotions were examined as potential mediating factors between difficulties in emotion regulation (DER) and engagement in SMAs. Finally, a moderated mediation model tested the effects of depressive symptoms in such relationships. RESULT: The emotional components associated with SMAs in reward/loss processing included activations in the left anterior insula (AI) and right dorsolateral prefrontal cortex (DLPFC) during anticipation of working to avoid losses. Activations in both the AI and DLPFC mediated the relationship between DER and SMAs. Moreover, depressive symptoms moderated the relationship between AI activation in response to loss anticipation and SMAs. CONCLUSION: The current findings suggest that DER link to SMAs through loss-related brain activations implicated in the processing of emotions and motivational avoidance, particularly in youth with greater levels of depressive symptoms. The findings suggest the importance of enhancing emotion-regulation tendencies/abilities in youth and, in particular, their regulatory responses to negative emotional situations in order to guide moderate engagement in SMAs.

Endovascular thrombectomy in acute ischemic stroke patients with prestroke disability (mRS ≥2): A systematic review and meta-analysis.

Objective: The effect of endovascular thrombectomy (EVT) in acute ischemic stroke patients with prestroke disability (modified Rankin Scale score, mRS) ≥2) has not been well-studied. This study aimed to assess the safety and benefit of EVT in patients with prestroke disability. Methods: According to PRISMA guidelines, literature searching was performed using PubMed, Embase, and Cochrane databases, for a series of acute ischemic stroke patients with prestroke mRS ≥2 treated by EVT. Random-effects meta-analysis was used to pool the rate of return to prestroke mRS and mortality at 3-month follow-up. Results: In total, 13 observational studies, with 2,625 patients, were analyzed. The rates of return to prestroke mRS in patients with prestroke mRS of 2-4 were 20% (120/588), 27% (218/827), and 31% (34/108), respectively. Patients with prestroke disability treated by EVT had a higher likelihood of return to prestroke mRS (relative risk, RR, 1.86; 95% CI 1.28-2.70) and a lower likelihood of mortality (RR 0.75; 95%CI 0.58-0.97) compared with patients with standard medical treatment. Successful recanalization (Thrombolysis in Cerebral Infarction grade 2b-3) after EVT gave a higher likelihood of return to prestroke mRS (RR 2.04; 95% CI 1.17-3.55) and lower mortality (RR 0.72; 95% CI 0.62-0.84) compared with unsuccessful reperfusion. Conclusions: Acute ischemic stroke patients with prestroke disability may benefit from EVT. Withholding EVT on the sole ground of prestroke disabilities may not be justified.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/.

[Silk fibroin/collagen composite hydrogels with different matrix stiffness influence the growth and phenotype of human mammary epithelial cells].

Extracellular matrix (ECM) stiffness is closely related to the physiological and pathological states of breast tissue. The current study was aimed to investigate the effect of silk fibroin/collagen composite hydrogels with adjustable matrix stiffness on the growth and phenotype of normal breast epithelial cells. In this study, the enzymatic reaction of horseradish peroxidase (HRP) with hydrogen peroxide (H2O2) was used to change the degree of cross-linking of the silk fibroin solution. The rotational rheometer was used to characterize the composite hydrogel's biomechanical properties. Human normal mammary epithelial cell line MCF-10A were inoculated into composite hydrogels with various stiffness (19.10-4 932.36 Pa) to construct a three dimensional (3D) culture system of mammary epithelial cells. The CCK-8 assay was applied to detect the cell proliferation rate and active states in each group. Hematoxylin-Eosin (HE) staining and whole-mount magenta staining were used for histological evaluation of cell morphology and distribution. The results showed that with the increase of matrix stiffness, MCF-10A cells exhibited inhibited proliferation rate, decreased formation of acinus structures and increased branching structures. Meanwhile, with the increase of matrix stiffness, the polarity of MCF-10A cells was impeded. And the increase of matrix stiffness up-regulated the expression levels of mmp-2, mmp-3, and mmp-9 in MCF-10A cells. Among the genes related to epithelial-mesenchymal transition (EMT), the expression level of the epithelial marker gene E-cadherin was significantly down-regulated, while the interstitial cell marker gene Vimentin was up-regulated, and the expression levels of Snail, Wnt5b and Integrin ß1 in the Wnt pathway were up-regulated. These results suggest that the silk fibroin/collagen composite hydrogels with adjustable matrix stiffness regulates the proliferation and the phenotype of MCF-10A cells. The effects of increased matrix stiffness may be closely related to the changes of the polar structures and function of MCF-10A cells, as well as the occurrence of ECM-remodeling and EMT.

Connectome-based prediction of marital quality in husbands' processing of spousal interactions.

Marital quality may decrease during the early years of marriage. Establishing models predicting individualized marital quality may help develop timely and effective interventions to maintain or improve marital quality. Given that marital interactions have an important impact on marital well-being cross-sectionally and prospectively, neural responses during marital interactions may provide insight into neural bases underlying marital well-being. The current study applies connectome-based predictive modeling, a recently developed machine-learning approach, to functional magnetic resonance imaging (fMRI) data from both partners of 25 early-stage Chinese couples to examine whether an individual's unique pattern of brain functional connectivity (FC) when responding to spousal interactive behaviors can reliably predict their own and their partners' marital quality after 13 months. Results revealed that husbands' FC involving multiple large networks, when responding to their spousal interactive behaviors, significantly predicted their own and their wives' marital quality, and this predictability showed gender specificity. Brain connectivity patterns responding to general emotional stimuli and during the resting state were not significantly predictive. This study demonstrates that husbands' differences in large-scale neural networks during marital interactions may contribute to their variability in marital quality and highlights gender-related differences. The findings lay a foundation for identifying reliable neuroimaging biomarkers for developing interventions for marital quality early in marriages.

Gender-related differences in involvement of addiction brain networks in internet gaming disorder: Relationships with craving and emotional regulation.

BACKGROUND: Abnormal interactions among addiction brain networks associated with intoxication, negative affect, and anticipation may have relevance for internet gaming disorder (IGD). Despite prior studies having identified gender-related differences in the neural correlates of IGD, gender-related differences in the involvement of brain networks remain unclear. METHODS: One-hundred-and-nine individuals with IGD (54 males) and 111 with recreational game use (RGU; 58 males) provided resting-state fMRI data. We examined gender-related differences in involvement of addiction brain networks in IGD versus RGU subjects. We further compared the strength between and within addiction brain networks and explored possible relationships between the strength of functional connectivities within and between addiction brain networks and several relevant behavioral measures. RESULTS: The addiction brain networks showed high correct classification rates in distinguishing IGD and RGU subjects in men and women. Male subjects with versus without IGD showed stronger functional connectivities between and within addiction brain networks. Moreover, the strength of the connectivity within the anticipation network in male IGD subjects was positively related to subjective craving. However, female subjects with versus without IGD showed decreased functional connections between and within addiction brain networks. The strength of connectivity between the anticipation and negative-affect brain networks in female IGD subjects was negatively related to maladaptive cognitive emotion-regulation strategies. CONCLUSIONS: Addiction brain networks have potential for distinguishing IGD and RGU individuals. Importantly, this study identified novel gender-related differences in brain-behavior relationships in IGD. These results help advance current neuroscientific theories of IGD and may inform gender-informed treatment strategies.

TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial-Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma.

Tumor necrosis factor (TNF)-like cytokine 1A (TL1A), a member of the TNF family, exists in the form of membrane-bound (mTL1A) and soluble protein (sTL1A). TL1A binding its only known functional receptor death domain receptor 3 (DR3) affects the transmission of various signals. This study first proposed that the TL1A/DR3 axis was significantly upregulated in patients and mice with both asthma and high TNF-a expression and in TNF-a-stimulated epithelial Beas-2B cells. Two independent approaches were used to demonstrate that the TL1A/DR3 axis of mice was strongly correlated with TNF-a in terms of exacerbating asthmatic epithelial-mesenchymal transformation (EMT). First, high expression levels of EMT proteins (e.g., collagen I, fibronectin, N-cadherin, and vimentin) and TL1A/DR3 axis were observed when mice airways were stimulated by recombinant mouse TNF-a protein. Moreover, EMT protein and TL1A/DR3 axis expression synchronously decreased after mice with OVA-induced asthma were treated with infliximab by neutralizing TNF-a activity. Furthermore, the OVA-induced EMT of asthmatic mice was remarkably improved upon the deletion of the TL1A/DR3 axis by knocking out the TL1A gene. TL1A siRNA remarkably intervened EMT formation induced by TNF-a in the Beas-2B cells. In addition, EMT was induced by the addition of high concentrations of recombinant human sTL1A with the cell medium. The TL1A overexpression via pc-mTL1A in vitro remarkably increased the EMT formation induced by TNF-a. Overall, these findings indicate that the TL1A/DR3 axis may have a therapeutic role for asthmatic with high TNF-a level.

Do Real-Time Strategy Video Gamers Have Better Attentional Control?

OBJECTIVE: Do real-time strategy (RTS) video gamers have better attentional control? To examine this issue, we tested experienced versus inexperienced RTS video gamers on multi-object tracking tasks (MOT) and dual-MOT tasks with visual or auditory secondary tasks (dMOT). We employed a street-crossing task with a visual working memory task as a secondary task in a virtual reality (VR) environment to examine any generalized attentional advantage. BACKGROUND: Similar to action video games, RTS video games require players to switch attention between multiple visual objects and views. However, whether the attentional control advantage is limited by sensory modalities or generalizes to real-life tasks remains unclear. METHOD: In study 1, 25 RTS video game players (SVGP) and 25 non-video game players (NVGP) completed the MOT task and two dMOT tasks. In study 2, a different sample with 25 SVGP and 25 NVGP completed a simulated street-crossing task with the visual dual task in a VR environment. RESULTS: After controlling the effects of the speed-accuracy trade-off, SVGP showed better performance than NVGP in the MOT task and the visual dMOT task, but SVGP did not perform better in either the auditory dMOT task or the street-crossing task. CONCLUSION: RTS video gamers had better attentional control in visual computer tasks, but not in the auditory tasks and the VR tasks. Attentional control benefits associated with RTS video game experience may be limited by sensory modalities, and may not translate to performance benefits in real-life tasks.

Reward-related decision-making deficits in internet gaming disorder: a systematic review and meta-analysis.

AIMS: To estimate the aggregated effect sizes of reward-related decision-making deficits in internet gaming disorder (IGD) and to explore potential moderators on the variability of effect sizes across studies. DESIGN: Review of peer-reviewed studies comparing reward-related decision-making performance between IGD and control participants identified via PubMed, Web of Science and ProQuest databases. Random-effects modeling was conducted using Hedge's g as the effect size (ES). The effects of decision-making situation, valence, sample type, testing environment, IGD severity and self-reported impulsivity on decision-making differences were examined by moderator analyses. SETTING: No restrictions on location. PARTICIPANTS: Twenty-four studies (20 independent samples) were included in the meta-analysis, resulting in 604 IGD and 641 control participants and 35 ESs. MEASURES: Reward-related decision-making differences between IGD and control groups. FINDINGS: The overall ES for decision-making deficits in IGD was small (g = -0.45, P < 0.01). The effects were comparable across risky, ambiguous and inter-temporal decision-making. Larger aggregate ESs were identified for pure-gain and mixed compared with pure-loss decision-making. Studies based on clinical and community samples showed similar effects. No significant difference between behavioral studies and those with extra measurements was observed. Decision-making alterations were not closely associated with IGD severity or self-reported impulsivity differences at the study level. CONCLUSIONS: Internet gaming disorder appears to be consistently associated with reward-related decision-making deficits.

Neural classification of internet gaming disorder and prediction of treatment response using a cue-reactivity fMRI task in young men.

BACKGROUND: Neural mechanisms underlying internet gaming disorder (IGD) are important for diagnostic considerations and treatment development. However, neurobiological underpinnings of IGD remain relatively poorly understood. METHODS: We employed multi-voxel pattern analysis (MVPA), a machine-learning approach, to examine the potential of neural features to statistically predict IGD status and treatment outcome (percentage change in weekly gaming time) for IGD. Cue-reactivity fMRI-task data were collected from 40 male IGD subjects and 19 male healthy control (HC) subjects. 23 IGD subjects received 6 weeks of craving behavioral intervention (CBI) treatment. MVPA was applied to classify IGD subjects from HCs and statistically predict clinical outcomes. RESULTS: MVPA displayed a high (92.37%) accuracy (sensitivity of 90.00% and specificity of 94.74%) in the classification of IGD and HC subjects. The most discriminative brain regions that contribute to classification were the bilateral middle frontal gyrus, precuneus, and posterior lobe of the right cerebellum. MVPA statistically predicted clinical outcomes in the craving behavioral intervention (CBI) group (r = 0.48, p = 0.0032). The most strongly implicated brain regions in the prediction model were the right middle frontal gyrus, superior frontal gyrus, supramarginal gyrus, anterior/posterior lobes of the cerebellum and left postcentral gyrus. CONCLUSIONS: The findings about cue-reactivity neural correlates could help identify IGD subjects and predict CBI-related treatment outcomes provide mechanistic insight into IGD and its treatment and may help promote treatment development efforts.

Syndecan-1 Shedding by Matrix Metalloproteinase-9 Signaling Regulates Alveolar Epithelial Tight Junction in Lipopolysaccharide-Induced Early Acute Lung Injury.

INTRODUCTION: Alveolar epithelial tight junction damage and glycocalyx syndecan-1 (SDC-1) degrading are key factors to pulmonary edema of acute lung injury (ALI). Matrix metalloproteinase-9 (MMP-9) was involved in glycocalyx shedding, which was vital in SDC-1 degrading. This study aimed to investigate the effects of MMP-9-mediated SDC-1 shedding on tight junction in LPS-induced ALI. METHODS: Mice were intratracheally atomized with 5 mg/kg LPS to stimulate different periods and LPS stimulation for 6 hours for further studies. A549 cells was stimulated for 6 hours by active MMP-9 protein to assess the effects of active MMP-9 protein on SDC-1 and tight junction. Afterward, the mice treated with MMP-9 shRNA or A549 cells were treated with MMP-9 siRNA before LPS stimulation for 6 hours to explore the effects on glycocalyx SDC-1 and tight junction. Moreover, the mice were treated with recombinant SDC-1 protein or A549 cells were over-expressed by pc-SDC-1 before LPS stimulation for 6 hours to explore the effects of SDC-1 on tight junction. RESULTS: The mice persistent exposure to LPS showed that MMP-9 expression, glycocalyx SDC-1 shedding (SDC-1 decreased in alveolar epithelium and increased in the BALF), tight junction impairment, FITC-albumin infiltration, and other phenomena began to appear after 6 hours of LPS treatment in this study. The levels of SDC-1 and tight junction significantly decreased by active MMP-9 protein stimulation for 6 hours in the A549 cells. Therefore, LPS stimulation for six hours was selected for investigating the underlying effects of MMP-9-mediated SDC-1 shedding on the alveolar epithelial tight junction and pulmonary edema. Further vivo analysis showed that down regulation MMP-9 expression by MMP-9 shRNA significantly alleviated glycocalyx SDC-1 shedding (SDC-1 increased in alveolar epithelium and decreased in the BALF), tight junction (occludin and ZO-1) damage, and FITC-albumin infiltration in LPS-induced early ALI mice. The vitro results also showed that MMP-9 siRNA alleviated glycocalyx SDC-1 shedding (SDC-1 increased in cell culture medium and decreased in cell surface) and tight junction damage by downregulating MMP-9 expression in LPS-stimulated A549 cells. In addition, pretreatment with recombinant mouse SDC-1 protein significantly alleviated glycocalyx (SDC-1 increased in alveolar epithelium) and tight junction damage, and FITC-albumin infiltration in LPS-induced early ALI mice. Overexpression SDC-1 by pc-SDC-1 also significantly decreased tight junction damage in LPS-stimulated A549 cells. CONCLUSION: Glycocalyx SDC-1 shedding mediated by MMP-9 significantly aggravated tight junction damage, which further increased the pulmonary edema.

Syndecan-1 Amplifies Ovalbumin-Induced Airway Remodeling by Strengthening TGFß1/Smad3 Action.

Syndecan-1 (SDC-1) is a transmembrane proteoglycan of heparin sulfate that can regulate various cell signal transduction pathways in the airway epithelial cells and fibroblasts. Airway epithelial cells and human bronchial fibroblasts are crucial in airway remodeling. However, the importance of SDC-1 in the remodeling of asthmatic airways has not been confirmed yet. The present study was the first to uncover SDC-1 overexpression in the airways of humans and mice with chronic asthma. This study also validated that an increase in SDC-1 expression was correlated with TGFß1/Smad3-mediated airway remodeling in vivo and in vitro. A small interfering RNA targeting SDC-1 (SDC-1 siRNA) and homo-SDC-1 in pcDNA3.1 (pc-SDC-1) was designed to assess the effects of SDC-1 on TGFß1/Smad3-mediated collagen I expression in Beas-2B (airway epithelial cells) and HLF-1 (fibroblasts) cells. Downregulation of the SDC-1 expression by SDC-1 siRNA remarkably attenuated TGFß1-induced p-Smad3 levels and collagen I expression in Beas-2B and HLF-1 cells. In addition, SDC-1 overexpression with pc-SDC-1 enhanced TGFß1-induced p-Smad3 level and collagen I expression in Beas-2B and HLF-1 cells. Furthermore, the levels of p-Smad3 and collagen I induced by TGFß1 were slightly increased after the addition of the recombinant human SDC-1 protein to Beas-2B and HLF-1 cells. These findings in vitro were also confirmed in a mouse model. A short hairpin RNA targeting SDC-1 (SDC-1 shRNA) to interfere with SDC-1 expression considerably reduced the levels of p-Smad3 and remodeling protein (α-SMA, collagen I) in the airways induced by ovalbumin (OVA). Similarly, OVA-induced p-Smad3 and remodeling protein levels in airways increased after mice inhalation with the recombinant mouse SDC-1 protein. These results suggested that SDC-1 of airway epithelial cells and fibroblasts plays a key role in the development of airway remodeling in OVA-induced chronic asthma.

Efficient Brain Connectivity Reconfiguration Predicts Higher Marital Quality and Lower Depression.

Social-information processing is important for successful romantic relationships and protecting against depression, and depends on functional connectivity (FC) within and between large-scale networks. Functional architecture evident at rest is adaptively reconfigured during task and there were two possible associations between brain reconfiguration and behavioral performance during neurocognitive tasks (efficiency effect and distraction-based effect). This study examined relationships between brain reconfiguration during social-information processing and relationship-specific and more general social outcomes in marriage. Resting-state FC was compared with FC during social-information processing (watching relationship-specific and general emotional stimuli) of 29 heterosexual couples, and the FC similarity (reconfiguration efficiency) was examined in relation to marital quality and depression 13 months later. The results indicated wives' reconfiguration efficiency (globally and in visual association network) during relationship-specific stimuli processing was related to their own marital quality. Higher reconfiguration efficiency (globally and in medial frontal, frontal-parietal, default mode, motor/sensory and salience networks) in wives during general emotional stimuli processing was related to their lower depression. These findings suggest efficiency effects on social outcomes during social cognition, especially among married women. The efficiency effects on relationship-specific and more general outcome are respectively higher during relationship-specific stimuli or general emotional stimuli processing.