Altered Heart Rate Variability During Mobile Game Playing and Watching Self-Mobile Gaming in Individuals with Problematic Mobile Game Use: Implications for Cardiac Health.

Introduction: The surge in mobile gaming, fueled by smartphone and internet accessibility, lacks a comprehensive understanding of physiological changes during gameplay. Methods: This study, involving 93 participants (average age 21.75 years), categorized them into Problematic Mobile Gaming (PMG) and non-problematic Mobile Gaming (nPMG) groups based on Problematic Mobile Gaming Questionnaire (PMGQ) scores. The PMGQ is a 12-item scale developed in Taiwan to assess symptoms of problematic mobile gaming. The research delved into heart rate variability (HRV) alterations during real-time mobile gaming and self-gaming video viewing. Results: Results showed that the PMG group significantly presents a lower root mean square of successive differences (RMSSD), and High Frequency (lnHF) than does the nPMG group (F=4.73, p=0.03; F=10.65, p=0.002, respectively) at the baseline. In addition, the PMG group significantly displayed elevated HF and low-frequency to high-frequency (LF/HF) in the mobile-gaming (F=7.59, p=0.007; F=9.31, p=0.003) condition as well as in the watching self-gaming videos (F=9.75, p=0.002; F=9.02, p=0.003) than did the nPMG. Conclusion: The study suggests targeted interventions to mitigate autonomic arousal, offering a potential avenue to address adverse effects associated with problematic mobile gaming behavior. The PMG group displayed increased craving scores after real-time mobile gaming and watching self-gaming video excerpts, unlike the nPMG group. Elevated LF/HF ratios in frequent gaming cases heightened autonomic arousal, presenting challenges in relaxation after mobile gaming. These findings contribute to a nuanced understanding of the complex interplay between mobile gaming activities, physiological responses, and potential intervention strategies.

Why Do People Watch Pornography? Cross-Cultural Validation of the Pornography Use Motivations Scale (PUMS) and Its Short Form (PUMS-8).

Motivations for pornography use may vary across gender identities, sexual orientations, and geographical regions, warranting examination to promote individual and public health. The aims of this study were to validate the Pornography Use Motivations Scale (PUMS) in a diverse, multicultural sample, and develop a short form (PUMS-8) that can assess a wide range of pornography use motivations. Using data from 42 countries (N = 75,117; Mage = 32.07; SDage = 12.37), enabled us to thoroughly evaluate the dimensionality, validity, and reliability of the Pornography Use Motivations Scale (PUMS), leading to the development of the more concise PUMS-8 short scale. Additionally, language-, nationality-, gender-, and sexual-orientation-based measurement invariance tests were conducted to test the comparability across groups. Both the PUMS and the PUMS-8 assess eight pornography use motivations, and both demonstrated excellent psychometric properties. Sexual Pleasure emerged as the most frequent motivation for pornography use across countries, genders, and sexual orientations, while differences were observed concerning other motivations (e.g. self-exploration was more prevalent among gender-diverse individuals than men or women). The motivational background of pornography use showed high similarity in the examined countries. Both the PUMS and the PUMS-8 are reliable and valid measurement tools to assess different types of motivations for pornography use across countries, genders, and sexual orientations. Both scales are recommended for use in research and clinical settings.

AccessPD as a next generation registry to accelerate Parkinson's disease research.

Recruitment is a major rate-limiting factor in Parkinson's disease (PD) research. AccessPD is a unique platform that aims to create a registry of more than 2000 PD patients and a rich database of PD-relevant information. Potential participants are identified using electronic health records (EHRs) in primary care. They are contacted via text message with an individualized link to the study portal. Electronic patient-reported outcomes (ePRO) are collected via online questionnaires and integrated with existing EHR. 200 participants were recruited within the first 6 months, of which 191 answered the follow-up questionnaire. Here, to showcase the potential of AccessPD, we described the most common diagnoses before and after PD diagnosis, the most commonly prescribed drugs, and identified participants who could benefit from device-aided therapies using consensus criteria. AccessPD shows its unique ability to link different data sources for patient stratification in longitudinal studies and recruitment into clinical trials.

The effect of age and resilience on the dose-response function between the number of adversity factors and subjective well-being.

Background: Encountering challenges and stress heightens the vulnerability to mental disorders and diminishes well-being. This study explores the impact of psychological resilience in the context of adverse events, considering age-related variations in its influence on well-being. Methods: A total of 442 participants (male vs. female =48% vs. 52%) with a mean age of 41.79 ± 16.99 years were collected and completed the following questionnaires Brief Betrayal Trauma Survey (BBTS), Brief Resilience Scale (BRS), Peace of Mind (PoM), The World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Social Support Questionnaire (SSQ). They all underwent structural and resting-state functional magnetic resonance imaging (MRI) scans. Results: Participants were categorized based on adversity levels: 34.39% faced one, 26.24% none, and 19.91, 9.50, and 8.14% encountered two, three, and four adversities, respectively. This categorization helps assess the impact on participants' experiences. As adversity factors increased, PoM decreased. Controlling for age improved PoM model fit (ΔR2 = 0.123, p < 0.001). Adversity factors and age explained 14.6% of PoM variance (df = 2, F = 37.638, p < 0.001). PoM decreased with more adversity and increased with higher age. Conclusion: The study found most participants faced at least one adversity. Adversity negatively affected PoM scores, while resilience acted as a protective factor. Resilience plays a crucial role in buffering the impact of adversities on well-being. Among those with high adversity, higher resilience correlated with stronger DMN-right frontal pole connectivity. Brain volume showed no significant differences, but the quality of life and social support varied between subgroups, with no differences in personal demographic and biophysical features.

Discrepancy of social cognition between bipolar disorders and major depressive disorders.

BACKGROUND: The research landscape examining social cognition (SC) impairment in patients with major depressive disorders (MDD) and bipolar disorders (BD) is notably scarce. Presently, assessments predominantly rely on static stimuli and self-reported measures, which may not capture the dynamic dimensions of social cognition. OBJECTIVES: This study aimed to validate the Chinese version of Movie Assessment of Social Cognition (MASC-CH) and to investigate whether MDD and BD exhibit distinct patterns of SC impairments, shedding light on potential differences between these two mood disorders. METHODS: The study encompassed 197 participants, aged 18-65, distributed as follows: 21 BD, 20 MDD, and 156 healthy controls (HC). We focused on examining "cognitive" and "emotional" SC scores and "undermentalizing" and "overmentalizing" error patterns, with nonsocial inference as a control. Additional assessments included the Reading Mind in the Eyes Test (RMET) and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). We also explored the association between depression severity (measured by the Hamilton Depressive Rating Scale, HDRS) and distinct SC dimensions between MDD and BD. RESULTS: The MASC-CH exhibited strong validity and reliability for SC assessment. In group comparisons, BD participants scored significantly lower on MASC-CH, while the MDD group scores were not significantly different from HC. Specifically, BD individuals had notably lower cognitive SC scores and made more undermentalizing and absence of mentalizing errors than MDD and HC. Additionally, a negative correlation between HDRS score and overmentalizing was observed in BD, not in the MDD. CONCLUSIONS: The findings indicate that depression severity scores in BD were inversely related to MASC-CH scores. In contrast, this relationship was not observed in the MDD group. These results underscore the importance of SC impairments as distinguishing characteristics of both BD and MDD. It provides valuable insights into the distinct social-cognitive profiles of both mood disorders.

The role of attitudes towards contradiction in psychological resilience: the cortical mechanism of conflicting resolution networks.

Managing contradictions and building resilience help us overcome life's challenges. Here, we explored the link between attitudes towards contradictions and psychological resilience, examining the role of cortical conflict resolution networks. We enlisted 173 healthy young adults and used questionnaires to evaluate their cognitive thinking styles and resilience. They underwent structural and functional magnetic resonance imaging scans. Our results revealed that contrasting attitudes toward contradictions, formal logic, and naïve dialecticism thinking styles corresponded with varying degrees of resilience. We noted structural and functional differences in brain networks related to conflict resolution, including the inferior frontal and parietal cortices. The volumetric variations within cortical networks indicated right-hemispheric lateralization in different thinking styles. These findings highlight the potential links between conflict resolution and resilience in the frontoparietal network. We underscore the importance of frontoparietal brain networks for executive control in resolving conflicting information and regulating the impact of contradictions on psychological resilience.

Weight stigma is associated with body mass index among college students in Taiwan: the mediated role of internalized weight stigma.

BACKGROUND: Weight stigma is an issue often studied in Western countries; however, such information is scarce in Asian studies. METHODS: This study aimed to examine the role of internalized weight stigma as a mediator in the relationship between perceived weight stigma and changes in body mass index (BMI). The data were collected through a longitudinal online survey with two phases (n = 974; Phase 1: August and September 2021; Phase 2: November and December 2021). The Perceived Weight Stigma Scale (PWSS), Weight Self-Stigma Questionnaire (WSSQ), and Depression, Anxiety, Stress Scale - 21 (DASS-21) were administered to assess perceived weight stigma, internalized weight stigma, and psychological distress. Hierarchical regressions were used to examine the proposed model, and Hayes' Process Macro was used to test a mediation model. RESULTS: The changes in perceived weight stigma and internalized weight stigma were significantly and positively associated with changes in BMI. There were significant and positive associations between perceived weight stigma, internalized weight stigma and psychological distress over time. Change in internalized weight stigma was found to be a significant mediator in the association of change in perceived weight stigma with change in BMI for the entire sample (unstandardized coefficient = 0.04; 95% CI = 0.02, 0.06), female subgroup (unstandardized coefficient = 0.05; 95% CI = 0.02, 0.08), and male subgroup (unstandardized coefficient = 0.03; 95% CI = 0.01, 0.06). Change in perceived weight stigma also had significant effects on change in BMI for the entire sample and the female subgroup, but not for the male subgroup. CONCLUSION: Because perceived weight stigma may significantly impact changes in BMI through internalized weight stigma, treatment strategies to ameliorate self-stigma may enhance the results of weight-reduction programs. Such treatment strategies should be considered for inclusion in weight-loss interventions.

Weight stigma is commonly studied in Western countries rather than in Asian ones. To further explore how internalized weight stigma mediates the relationship between perceived weight stigma and the changes in body mass index (BMI), the study collected data through a longitudinal online survey with two phases by applying the Perceived Weight Stigma Scale (PWSS), Weight Self-Stigma Questionnaire (WSSQ) and Depression, Anxiety, Stress Scale − 21 (DASS-21) to assess perceived weight stigma, internalized weight stigma, and psychological distress. The changes in perceived and internalized weight stigma were significantly and positively associated with changes in BMI. There were significantly positive associations between perceived weight stigma, internalized weight stigma, and psychological distress over time. Based on the findings, treatment strategies to alleviate self-stigma may enhance the results of weight-reduction programs and should be considered for inclusion in weight-loss interventions.

Measurement Invariance and Psychometric Evaluation of the Tendency to Avoid Physical Activity and Sport Scale (TAPAS) Among Mainland Chinese University Students.

Introduction: Preventative factors in young people's physical inactivity require further understanding, including related psychosocial factors (eg, body image and weight stigma). The Tendency to Avoid Physical Activity and Sport Scale (TAPAS) is a recently developed instrument to address this issue and the present study examined its psychometric properties among Chinese university students particularly in relation to patterns across sex, physical activity (PA) level, and weight status. Methods: Using a convenience sample of 3142 students (mean age = 19.8 years; 56% female) in mainland China, data were collected using an online survey between August and October 2022. Psychometric instruments including the Weight Bias Internalization Scale, 21-item Depression, Anxiety and Stress Scale, and International Physical Activity Questionnaire Short Form were administered along with the TAPAS to assess convergent and discriminant validity. Multi-group confirmatory factor analysis (CFA) assessed the measurement invariance across specific groups. Results: The unidimensional structure of the scale was confirmed through CFA (CFI=0.995; RMSEA=0.046). All configural, metric and scalar models of invariance indicated that the scale was invariant across sex, PA level, and weight status. Acceptable convergent and discriminant validity for the scale were found. Conclusion: The TAPAS is a suitable instrument to assess body image and weight stigma concerns for avoiding physical activity and sport among Chinese university students.

Effects of comorbid alcohol use disorder on bipolar disorder: Focusing on neurocognitive function and inflammatory markers.

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers. METHOD: We recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-ß1 (TGF-ß1), and brain-derived neurotrophic factor (BDNF)] were assessed. RESULTS: BD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05). CONCLUSION: Our results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.

Social support enhances the mediating effect of psychological resilience on the relationship between life satisfaction and depressive symptom severity.

Psychosocial factors, including life satisfaction, resilience, and social support, have been proposed to influence depressive symptom severity in adults because the age of onset of depressive disorders, i.e. adolescence to early adulthood, is associated with various impairments in psychosocial functioning. In this study, a psychosocial model was constructed to verify these relationships to prevent depression. For this study, 370 participants were recruited from the community via poster or online advertisements. They completed several questionnaires to assess depressive symptom severity: the Connor-Davidson Resilience Scale (CD-RISC), Satisfaction with Life Scale (SwLS), Peace of Mind (PoM) scale, Social Support Questionnaire (SSQ), and Beck Depression Inventory (BDI-II). A negative association was found between depressive symptom severity and all other variables, including PoM and CD-RISC scores, life satisfaction, and social support. Such factors can be considered protective against increased depressive symptom severity. In addition, indirect effects of PoM and resilience on the negative association between SwLS scores and depressive symptom severity were observed. Moreover, social support was found to mediate the correlation between PoM and resilience, implying that social support mediates the relationship between state of mind and resilience. The psychosocial model suggested that depressive symptom severity is influenced by internal factors (an individual's state of mind, subjective view of events and their life) and external factors (including social support).

The Mediating Role of Brain Structural Imaging Markers in Connecting Adverse Childhood Experiences and Psychological Resilience.

The impact of adverse childhood experiences (ACEs) on brain structure has been noticed. Resilience has been considered a protective characteristic from being mentally ill; however, the link between ACEs, psychological resilience, and brain imaging remains untested. A total of 108 participants (mean age 22.92 ± 2.43 years) completed the ACEs questionnaire and the Resilience Scale for Adults (RSA), with five subscales: personal strength (RSA_ps), family cohesion (RSA_fc), social resources (RSA_sr), social competence (RSA_sc), and future structured style (RSA_fss), and Magnetic Resonance Imaging (MRI) to acquire imaging data, and the fusion-independent component analysis was employed to determine multimodal imaging components. The results showed a significantly negative association between ACE subscales and RSA_total score (ps < 0.05). The parallel mediation model showed significant indirect mediation of mean gray matter volumes in the regions of the middle frontal gyrus, superior frontal gyrus, posterior cingulate, superior temporal gyrus, middle temporal gyrus, postcentral gyrus, middle temporal gyrus, and precuneus between childhood maltreatment and RSA_sr and RSA_sc. (ps < 0.05). This study highlighted the ACEs effect on gray matter volumes in the regions of the middle frontal gyrus, superior frontal gyrus, posterior cingulate, superior temporal gyrus, middle temporal gyrus, postcentral gyrus, middle temporal gyrus, and precuneus leading to decreased psychological resilience.

The effectiveness of child-centered play therapy for executive functions in children with attention-deficit/hyperactivity disorder.

INTRODUCTION: Child-centered play therapy (CCPT) is a practical and recommended non-medication intervention for children with Attention-deficit/hyperactivity disorder (ADHD) but the mechanism in between is unclear. AIM: This study proposed to examine the effectiveness of CCPT on neuropsychological deficits and behavioral symptoms in ADHD. METHODS: Participants with ADHD diagnosis were referred from senior child and adolescent psychiatrists, and typical developmental children (TD) were recruited from community as a control group. All participants' executive functions were evaluated using Cambridge Neuropsychological Test Automated Battery. First of all, the participants were evaluated using Child Behavior Checklist (CBCL) by their parents. The ADHD participants were assigned into CCPT (ADHDc) and waitlist (ADHDw) group; and the ADHDc group then received CCPT weekly for 12 sessions, while the ADHDw continuously received their regular treatment (i.e., medication treatment or other alternative treatments) as usual. RESULTS: Total 52 participants were recruited (17 with ADHD and 35 typically developed children, TD). The results showed that overall the ADHD groups had worse neuropsychological performance and more behavioural disturbance than did the TD (ps < .05). After receiving the CCPT, the results showed that the ADHDc group had significant improvement in the cognitive flexibility (p < .05); while the ADHDw group had no changes.

Association Between Inflammatory Cytokines, Executive Function, and Substance Use in Patients With Opioid Use Disorder and Amphetamine-Type Stimulants Use Disorder.

BACKGROUND: Long-term opioid and amphetamine-type stimulants (ATS) abuse may affect immunological function and impair executive function. We aimed to determine whether biomarkers of inflammation and executive function were associated with substance use in individuals with opioid use disorder (OUD) and ATS use disorder (ATSUD). The interactions between these biomarkers were also explored. METHODS: We assessed plasma cytokines [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-8, IL-6, transforming growth factor (TGF)-ß1, brain-derived neurotrophic factor (BDNF), and executive function in terms of the Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) in OUD and ATSUD patients and healthy controls (HC). OUD and ATSUD patients were followed for 12 weeks, and their urine morphine and amphetamine tests, cytokine levels, and executive function were repeatedly measured. RESULTS: We enrolled 483 patients and 145 HC. Plasma TNF-α, CRP, IL-8, IL-6, and BDNF levels and most subscale scores on the WCST and CPT significantly differed between OUD and ATSUD patients and HC. Increased TNF-α levels and more perseveration error on the WCST were significantly associated with more urine drug-positive results and less abstinence. Plasma IL-6 and CRP levels were significantly negatively correlated with WCST and CPT performance. CONCLUSION: OUD and ATSUD patients had more inflammation and worse executive function than HC. Inflammatory markers and WCST performance were associated with their urinary drug results, and higher inflammation was associated with poor executive function. Studies on regulating the inflammatory process and enhancing executive function in OUD and ATSUD are warranted.

A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.

Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n = 94; £ = 41.97 m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.

Dynamic weight status changes and peer lifestyles in early adolescence: A social network analysis on a longitudinal cohort of Taiwanese youth.

BACKGROUND: Friendship networks are relevant to adolescent weight status and lifestyle, but little is known about their relationship in an East Asian setting. Using a longitudinal cohort of Taiwanese adolescents, we studied how weight status and lifestyles might influence friendship. Simultaneously considering the influence of friendship networks, we further examined the effects of peers' lifestyles on the body weight status of adolescents. METHODS: Data were retrieved from the first three waves of the Taiwan Youth Project (N = 2409; 51 % boys). Participants were asked to nominate their friends at school and to report their lifestyle factors (e.g. sleep habits, internet use, and athletic performance). Weight status was proxied by body mass index calculated from self-reported weight and height. Stochastic actor-based modeling was used for the friendship network analyses. RESULTS: Considering network structure, adolescents selected friends based on similarities in weight status (ß = 0.147 [standard error = 0.044], p < 0.001) and lifestyle factors, such as athletic performance (ß = 0.181 [0.034], p < 0.001), internet use (ß = 0.156 [0.039], p < 0.001), and social jetlag (ß = 0.055 [ ± 0.022], p < 0.05). In the behavior dynamics model, we did not observe any peer influence on changes in adolescents' weight status. CONCLUSION: These findings suggest a pervasive homophilic friendship selection explained by weight and lifestyle-based similarities, despite no evidence of peer influence on weight status. Stakeholders and care providers of adolescent health should be aware of the social network processes that underlie weight problems.

Co-inhibition of Aurora A and Haspin kinases enhances survivin blockage and p53 induction for mitotic catastrophe and apoptosis in human colorectal cancer.

Colorectal cancer (CRC) is a leading cause and mortality worldwide. Aurora A and haspin kinases act pivotal roles in mitotic progression. However, the blockage of Aurora A and Haspin for CRC therapy is still unclear. Here we show that the Haspin and p-H3T3 protein levels were highly expressed in CRC tumor tissues of clinical patients. Overexpression of Haspin increased the protein levels of p-H3T3 and survivin in human CRC cells; conversely, the protein levels of p-H3T3 and survivin were decreased by the Haspin gene knockdown. Moreover, the gene knockdown of Aurora A induced abnormal chromosome segregation, mitotic catastrophe, and cell growth inhibition. Combined targeted by co-treatment of CHR6494, a Haspin inhibitor, and MLN8237, an Aurora A inhibitor, enhanced apoptosis and CRC tumor inhibition. MLN8237 and CHR6494 induced abnormal chromosome segregation and mitotic catastrophe. Meanwhile, MLN8237 and CHR6494 inhibited survivin protein levels but conversely induced p53 protein expression. Ectopic survivin expression by transfection with a survivin-expressed vector resisted the cell death in the MLN8237- and CHR6494-treated cells. In contrast, the existence of functional p53 increased the apoptotic levels by treatment with MLN8237 and CHR6494. Co-treatment of CHR6494 and MLN8237 enhanced the blockage of human CRC xenograft tumors in nude mice. Taken together, co-inhibition of Aurora A and Haspin enhances survivin inhibition, p53 pathway induction, mitotic catastrophe, apoptosis and tumor inhibition that may provide a potential strategy for CRC therapy.

Transformed extracellular vesicles with high angiogenic ability as therapeutics of distal ischemic tissues.

Introduction: The therapeutic effects of endothelial progenitor cells (EPC) in neovascularization have been suggested; however, to date, few studies have been conducted on the ability of EPC-derived extracellular vesicles (EV) to rescue the ischemic tissues. In order to examine the functional sources of EV for cell-free therapy of ischemic diseases, we compared the functions of EPC-EV and those of Wharton's Jelly-derived mesenchymal stem cell (WJ-EV) in the flap mouse model. Results and conclusion: Our results demonstrated that in the intravenous injection, EPC-EV, but not WJ-EV, were uptaken by the ischemic tissues. However, EPC-EV showed poor abilities to induce neovascularization and the recovery of ischemic tissues. In addition, compared to EPC-EV, WJ-EV showed a higher ability to rescue the ischemic injury when being locally injected into the mice. In order to induce the secretion of high-functional EPC-EV, EPC were internalized with hypoxic pre-treated WJ-EV, which resulted in a transformed hwEPC. In comparison to EPC, hwEPC showed induced proliferation and upregulation of angiogenic genes and miRNAs and promoted angiogenic ability. Interestingly, hwEPC produced a modified EV (hwEPC-EV) that highly expressed miRNAs related to angiogenesis, such as miR-155, miR-183, and miR-296. Moreover, hwEPC-EV significantly induced the neovascularization of the ischemic tissues which were involved in promoting the proliferation, the expression of VEGF and miR-183, and the angiogenic functions of endothelial cells. Of note, hwEPC-EV were highly uptaken by the ischemic tissues and showed a greater effect with regard to inducing recovery from ischemic injury in the intravenous administration, compared to EPC-EV. Therefore, hwEPC-EV can be considered a functional candidate for cell-free therapy to treat the distal ischemic tissues.

Relationship Between Weight Status and Self-Image Mediated by Pubertal Timing and Athletic Competence: A Cohort Study With Taiwanese Adolescents.

Background: Self-image reflects overall self-acceptance in developing adolescents. Using a representative cohort of Taiwanese youth, this study aims to explore the relationship between weight status, pubertal timing, athletic competence, and adolescent self-image. Methods: Data come from the Taiwan Youth Project that comprised a longitudinal cohort of adolescents (N = 2690, 51% males, Mage = 13.3 ± 0.5 years) surveyed annually from seventh grade. Self-image was measured by perceived satisfaction with appearance and physique. Weight status was proxied by self-reported body mass index (BMI; kg/m2). Pubertal timing was defined using the Pubertal Developmental Scale, which mainly measured physical changes in puberty. Athletic competence was assessed by experiences with participation in competitive sports and self-perceived talent for sports. Linear regression analysis was applied to test for an association between BMI and self-image. In order to test for mediating roles of pubertal timing and athletic competence, Hayes' PROCESS macro on SPSS was conducted applying 5,000 bootstrap resamples with 95% confidence intervals of the indirect effect. Results: BMI was inversely associated with self-image in both males (ß = -0.074, [-0.095, -0.053]) and females (ß = -0.095, [-0.122, -0.069]). The boot-strapped 95% confidence intervals indicated statistically significant mediating effects of pubertal timing (ß = -0.008, [-0.015, -0.001]) and athletic competence (ß = -0.006, [-0.011, -0.002]) in the link between BMI and self-image in females, whilst only athletic competence mediated this association (ß = -0.006, [-0.009, -0.002]) in males. Moreover, BMI at baseline were also associated with long-term self-image in males (ß = -0.037, [-0.057, -0.017]) and females (ß = 0.132, [0.073, 0.190]). Conclusions: Understanding the mediating factors may help enhance adolescents' self-image by providing guidance on healthy weight and physical activity behaviors according to different stages of pubertal progression.

Extracellular vesicles derived from Wharton's Jelly mesenchymal stem cells inhibit the tumor environment via the miR-125b/HIF1α signaling pathway.

Triple negative breast cancer (TNBC) is associated with worse outcomes and results in high mortality; therefore, great efforts are required to find effective treatment. In the present study, we suggested a novel strategy to treat TNBC using mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) to transform the behaviors and cellular communication of TNBC cells (BCC) with other non-cancer cells related to tumorigenesis and metastasis. Our data showed that, BCC after being internalized with EV derived from Wharton's Jelly MSC (WJ-EV) showed the impaired proliferation, stemness properties, tumorigenesis and metastasis under hypoxic conditions. Moreover, these inhibitory effects may be involved in the transfer of miRNA-125b from WJ-EV to BCC, which downregulated the expression of HIF1α and target genes related to proliferation, epithelial-mesenchymal transition, and angiogenesis. Of note, WJ-EV-internalized BCC (wBCC) showed transformed behaviors that attenuated the in vivo development and metastatic ability of TNBC, the angiogenic abilities of endothelial cells and endothelial progenitor cells and the generation of cancer-associated fibroblasts from MSC. Furthermore, wBCC generated a new EV with modified functions that contributed to the inhibitory effects on tumorigenesis and metastasis of TNBC. Taken together, our findings suggested that WJ-EV treatment is a promising therapy that results in the generation of wBCC to interrupt the cellular crosstalk in the tumor environment and inhibit the tumor progression in TNBC.

Type 2 Diabetes Mellitus Promotes the Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells into Cancer-Associated Fibroblasts, Induced by Breast Cancer Cells.

Triple-negative breast cancer (TNBC) is a highly aggressive and invasive type of breast cancer. In addition, type 2 diabetes mellitus (T2DM) is recognized as a risk factor for cancer metastasis, which is associated with mortality in patients with breast cancer. Cancer-associated fibroblasts (CAFs) generated from adipose tissue-derived mesenchymal stem cells (AT-MSCs) play a vital role in the progression of TNBC. However, to date, whether T2DM affects the ability of AT-MSCs to differentiate into CAFs is still unclear. In this study, we found that in coculture with TNBC cells [breast cancer cells (BCCs)] under hypoxic conditions, AT-MSCs derived from T2DM donors (dAT-MSCs) were facilitated to differentiate into CAFs, which showed fibroblastic morphology and the induced expression of fibroblastic markers, such as fibroblast activation protein, fibroblast-specific protein, and vimentin. This was involved in the higher expression of transforming growth factor beta receptor 2 (TGFßR2) and the phosphorylation of Smad2/3. Furthermore, T2DM affected the fate and functions of CAFs derived from dAT-MSCs. While CAFs derived from AT-MSCs of healthy donors (AT-CAFs) exhibited the markers of inflammatory CAFs, those derived from dAT-MSCs (dAT-CAFs) showed the markers of myofibroblastic CAFs. Of note, in comparison with AT-CAFs, dAT-CAFs showed a higher ability to induce the proliferation and in vivo metastasis of BCCs, which was involved in the activation of the transforming growth factor beta (TGFß)-Smad2/3 signaling pathway. Collectively, our study suggests that T2DM contributes to metastasis of BCCs by inducing the myofibroblastic CAFs differentiation of dAT-MSCs. In addition, targeting the TGFß-Smad2/3 signaling pathway in dAT-MSCs may be useful in cancer therapy for TNBC patients with T2DM.