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Anxiety and depression are highly comorbid mental health disorders with heterogeneous symptom patterns and poorly understood transdiagnostic mechanisms. This study aims to characterize latent subgroups, risk factors, and symptom-level interactions underlying depression-anxiety comorbidity across adolescents and adults in multi-ethnic Southwest China. The study included a total of 41,394 adolescents (aged 9-19) and 17,345 adults (aged 18-80). Adolescents were recruited using multistage stratified cluster sampling, whereas adults were recruited by convenience sampling. All participants completed a self-designed sociodemographic questionnaire, the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). Latent profile analysis identified subgroups, logistic regression analyzed risk/protective factors, and network analysis mapped symptom interactions and bridge nodes. This study found that three adolescent profiles emerged: high (11.66 %), moderate (31.95 %), and low/no depression-anxiety (56.39 %). Adults were classified into low/no comorbidity (90.63 %) and comorbid depression-anxiety (9.37 %). Risk factors for adolescents included female gender (OR = 2.77, 95 %CI: 2.55-3.00; OR = 1.59, 95 %CI: 1.52-1.67), higher grade levels (OR = 3.45, 95 %CI: 3.10-3.84; OR = 3.56, 95 %CI: 3.33-3.80), smoking (OR = 1.72, 95 %CI: 1.51-1.96; OR = 1.28, 95 %CI: 1.17-1.41),drinking (OR = 2.45, 95 %CI: 2.23-2.70; OR = 1.66, 95 %CI: 1.55-1.77), family instability (OR = 1.16, 95 %CI: 1.02-1.31; OR = 1.33, 95 %CI: 1.14-1.56) and "other" ethnic minority (OR = 1.15, 95 %CI: 1.04-1.26). For adults, female gender(OR = 1.68; 95 %CI: 1.44-1.97), living alone(OR = 1.37; 95 %CI: 1.14-1.65), poor self-rated health (OR = 0.13, 95 %CI: 0.11-0.15), and Dai ethnicity (OR = 0.70, 95 %CI: 0.49-0.96) predicted comorbidity. Network analysis revealed distinct bridge symptoms: adolescents in the high depression-anxiety group had five symptoms: depressed or sad mood (phq2), psychomotor agitation/retardation (phq8), nervousness or anxiety (gad1), restlessness (gad5), and irritable (gad6); however, adults with comorbidity had one symptom: afraid something will happen (gad7). This study identified three patterns of depression-anxiety comorbidity in adolescents and two in adults. Efforts should prioritize adolescents from "other" ethnic minorities, strengthening family and peer support, as well as smoking and drinking interventions for adolescents, and addressing social isolation, physical health, and catastrophizing cognition in adults may mitigate the comorbidity burden. Show less

To investigate the dose-response relationship between e-health literacy and light physical activity (LPA) in older adults is to provide evidence for targeted interventions that enhance e-health literacy and promote LPA, thereby advancing healthy aging. This study used a convenience sampling method to select two residential neighborhoods. Subsequently, a random cluster sampling approach was employed, resulting in a total final sample of 105 community-dwelling older adults (aged 60 and above) from these neighborhoods. A three-axis accelerometer (ActiGraph wGT3X-BT) recorded the older adults' LPA, and the Electronic Health Literacy Scale assessed their e-health literacy. Multiple linear regression was used to explore the dose-response relationship between LPA and e-health literacy and sub-dimension scores. Multiple linear regression revealed that both the overall e-health literacy score and its components were positively associated with daily LPA (Tables 2 and 3). However, the empirical impact varied substantially across components. For each 1-point increase, LPA increased by 2.8 min for the overall score, 11 min for judgment ability, and 19.4 min for decision-making ability, whereas the effect of application ability was statistically significant but minimal. Notably, the effect sizes of all e-health literacy components were substantially smaller than that of educational attainment (β = 0.638-0.947), which was the strongest predictor in all models. This study provides empirical evidence that higher e-health literacy and its specific sub-dimensions are positively associated with light physical activity (LPA) among community-dwelling older adults, with educational attainment emerging as a key independent predictor. These findings suggest that public health interventions aimed at promoting LPA could be enhanced by incorporating strategies to improve e-health literacy, particularly targeting older adults with lower educational backgrounds. The development of tailored, theory-informed programs based on these insights holds promise for fostering healthy aging at the community level. Show less

Our early study showed the vasoactive effects of soybean lecithin-derived lysophosphatidic acid (LPA). The finding indicates that the oral administration of LPA-rich supplements is beneficial to human health. Our studies have showed five beneficial effects of LPA in the upper digestive systems. First, we detected LPA at high levels in various herbs used in Chinese traditional medicine for the treatment of gastric ulcers, as well as other foods, including various vegetables. Second, we found human mixed saliva to be an LPA-rich biological fluid, suggesting its protective effect on human oral mucosa. Third, LPA levels in gingival crevicular fluid from patients with periodontitis was lower than that in healthy subjects, reinforcing the protective quality of LPA. Fourth, daily topical injections of LPA in rat buccal gingiva reduced the degree of alveolar bone absorption induced by oral bacteria in rats with experimental periodontitis. Fifth, repeated intragastric administration of LPA-rich herb reduced the degrees of gastric ulcer induced by stress (rats) or medication (mouse). Previous findings on the beneficial effects of LPA acting on the lumen side of the lower digestive tracts in mammals are well documented, although results on the harmful effects of LPA on mouse and rats with genetically easy to progress colon cancer are noted. Our studies also showed a novel pathway of LPA generation by lysophospholipase D activity of glycerophosphodiesterase 7 on the lumen side of digestive tracts. These findings suggest that additional research into creative food supplements focusing on LPA as a food factor could be beneficial. Show less

The COVID-19 pandemic has significantly disrupted educational style, potentially affecting the learning adaptation of nursing freshmen who are integral to the future nursing workforce. This study aimed to identify distinct subgroups of nursing freshmen based on their bioecological attributes related to learning adaptation during the pandemic. A multicenter, cross-sectional study was conducted of 1170 first-year nursing students from six higher education institutions in China. Learning adaptation, resilience, parental attachment, interaction anxiety, and mobile phone addiction, were investigated. Latent Profile Analysis (LPA) was utilized to identify distinct profiles. Descriptive statistics indicated a positive level of learning adaptation among participants, with an overall mean score of 3.51 ± 0.57. LPA revealed four distinct profiles: 'Struggling Learners' (5.47%), 'Moderate Engagers' (70.60%), 'Adaptable Strivers' (18.29%), and 'Optimal Adapters' (5.64%), which demonstrated significant differences in adaptation, resilience, parental attachment, interaction anxiety, and mobile phone addiction tendencies (P < 0.05). The study's findings emphasize the heterogeneity in learning adaptation among nursing freshmen and the importance of considering bioecological attributes when developing educational interventions during crisis. Recognizing these profiles can guide the development of targeted strategies to enhance student adaptation and academic achievement. Show less

This study aimed to investigate the relationship between blood uric acid (UA), serum lipoprotein(a) [Lp(a)], and the severity of neurological damage in patients with acute penetrating artery occlusive cerebral infarction combined with type 2 diabetes mellitus (T2DM). To evaluate the role of UA and Lp(a) levels as independent risk factors for neurological damage severity and poor prognosis, and to observe the therapeutic effect of tanshinone. Clinical data of patients were analyzed to compare differences in indicators between the mild and moderate groups, as well as between groups with good and poor prognosis. Patients in the moderate infarction group showed significantly higher levels of UA, Lp(a), and other biochemical markers, along with higher rates of unhealthy lifestyle habits and comorbidities. UA, Lp(a), and infarct diameter were independent risk factors for poor prognosis. Their combined prediction model demonstrated good sensitivity and specificity. Pre-treatment UA and Lp(a) levels were significantly positively correlated with pre-treatment NIHSS scores and post-treatment mRS scores, respectively. In patients with acute penetrating artery occlusive cerebral infarction combined with T2DM, blood uric acid and serum Lp(a) levels are associated with the severity of neurological damage and serve as independent risk factors for poor prognosis. Show less

Transfer between limbs in younger adults is typically asymmetrical, with greater changes observed in one limb following practice with the other limb, depending on the controlling hemisphere (Pan & van Gemmert). This asymmetry is linked to lateralized hemispheric control of movement (Sainburg), irrespective of high (HPA) or low (LPA) levels of physical activity (McGregor et al.). Acute exercise affects motor skill transfer (Neva et al.). The purpose of this study was to examine the effects of reported chronic physical activity level on bilateral transfer in young adults. Fifty young right-handed participants (18-30) were grouped by physical activity level and randomly assigned a training limb. Individuals performed a 30° visual rotation drawing task. Pretest established baseline performance of each limb, followed by 40 practice trials on the assigned limb. Post-tests mirrored pretests assessing changes. HPA improved movement time (MT), normalized jerk (NJ), trajectory length (TL), and initial direction error (IDE) in the dominant limb following non-dominant practice ( Show less

The assessment of serious illness communication (SIC) competence has, to date, primarily utilized tools that are profession-specific and not explicitly designed using competency-based or person-centered frameworks. To address these gaps, we developed and validated a new tool, the Assessment of Clinical Encounters - Communication Tool (ACE-CT). We convened a national panel of interprofessional SIC experts to develop and validate the ACE-CT using a three-phase multi-method approach. Phase 1 focused on item development through review of existing validated tools, and a Bayesian process in which panel members assessed item quality and item-domain correlation. Phase 2 involved item refinement and preliminary validation through stimulated recall interviews using a think-aloud technique. Phase 3 consisted of psychometric analyses for which panel members used the tool to assess video-recorded standardized patient encounters from interprofessional clinicians completing a SIC professional development intervention. In Phase 1, 37 relevant items from previously validated tools were identified, of which 11 items were removed due to redundance. Through the Bayesian process, 14 items were removed and 1 item was generated. Through Phase 2, 2 items were generated, 2 items were combined into 1, and remaining items were refined to optimize measurability and understandability. In Phase 3, reliability was demonstrated through evidence of high internal consistency and moderate reproducibility, both over time and across raters. The tool was found to be responsive and have sound construct validity through evidence of congruence, convergence and credibility. Raters found the tool to be intuitive, easy to complete, and that it accurately captured their perception of the quality of communication observed. The ACE-CT provides a reliable and valid approach to assessing SIC competence among interprofessional clinicians. Through its person-centered orientation, the ACE-CT provides an opportunity to objectively assess elements of SIC that patients and families value. Show less

This study explored how minority stress and social safety jointly shape mental health among Taiwanese sexual minority men (SMM) through the identification of psychosocial profiles and their associations with depression. Between April and May 2023, 415 Taiwanese SMM completed an online cross-sectional survey. Latent profile analysis (LPA) identified groups based on minority stress (sexuality-related discrimination, acceptance concerns, internalized homonegativity) and social safety (identity affirmation, family support, community connectedness) indicators. Multinomial logistic regression examined sociodemographic correlates of profile membership, and linear and binary logistic regressions assessed associations with depressive symptom severity (DSS) and major depressive disorder (MDD). LPA identified three distinct profiles: "Moderate Minority Stress-Low Social Safety" (MMS-LSS; These findings revealed diverse experiences of minority stress and social safety among Taiwanese SMM and their implications for depression, supporting culturally responsive interventions. Show less

Adolescent mental health issues have become a growing public health concern. This study seeks to identify potential profiles of mental health among Chinese adolescents and to detect high-risk groups for the formulation of targeted intervention strategies based on associated health risk behaviors (HRBs). A cross-sectional study. This study was based on the Monitoring and Intervention Project for Common Diseases and Health Influencing Factors among Secondary School Students in Nanjing, involving 9,865 secondary school students as participants. Latent profile analysis (LPA) was employed to identify mental health (symptoms of depression, anxiety, and stress, as well as sleep quality); categorical variables were analyzed by the chi-square test or Fisher's exact test, whereas multinomial logistic regression was used to examine associations between HRBs and distinct mental health profiles. Three profiles of mental health were identified among the adolescents, including "Low-risk Mental Health" (68.03 %), "Moderate-risk Mental Health" (26.19 %), and "High-risk Mental Health" (5.78 %). Compared with the "Low-risk Mental Health" profile, the "Moderate-risk Mental Health" profile was associated with behaviors such as drinking, injury, school bullying, unhealthy diet, internet addiction, physical activity, and outdoor activity time; and the "High-risk Mental Health" profile was associated with smoking, drinking, injury, school bullying, unhealthy diet, internet addiction, and outdoor activity time. Several HRBs are associated with mental health among Chinese adolescents. Healthcare professionals should target these HRBs and implement comprehensive measures to protect adolescent mental health. Show less

We describe a rare case of left pulmonary artery (LPA) originating from a closed left patent ductus arteriosus (PDA). A neonate underwent left PDA reopening and stenting. Reperfusion injury was minimized while allowing time for interval growth of the distal LPA. At four months of age, surgical reconstruction was performed to reconnect the LPA to the main pulmonary artery (MPA) with an anterior MPA flap augmented with pericardial patch. Autograft reconstruction is preferred to accommodate patients' growth. Postoperative angiogram showed confluent flow into LPA and distal pulmonary branches. Patient was discharged without complications and was well after 1 year. Show less

Lipoprotein(a) [Lp(a)] and PCSK9 are emerging lipid biomarkers implicated in atherogenesis and residual cardiovascular risk, but their relationship with coronary disease complexity in acute coronary syndrome (ACS) is unclear. This study evaluates their serum levels in first-episode ACS patients versus controls and explores their relationship with SYNTAX score-defined coronary severity. This single-centre observational study enrolled 160 patients presenting with their first episode of ACS (aged 18-75) and 40 age-matched healthy controls. All participants were free from lipid-lowering therapy and major comorbidities. Fasting serum samples were collected to measure the standard lipid profile, Lp(a), and PCSK9 levels. The severity of coronary artery disease was quantified using the SYNTAX score after coronary angiography. The ACS cohort (mean age 55.7 years; 73.1 % male) most frequently presented with STEMI (53.7 %). Traditional risk factors included smoking/tobacco use (48.8 %), diabetes (40.0 %), and hypertension (38.1 %). Median SYNTAX score was 19.4. Compared with controls, ACS patients had significantly lower HDL-C and higher LDL/HDL and cholesterol/HDL ratios. Lp(a) (38.9 vs. 15.9 mg/dL, p < 0.001) and PCSK9 (272.3 vs. 169.6 ng/mL, p < 0.001) were markedly elevated in ACS patients. Neither Lp(a) nor PCSK9 correlated with SYNTAX score. LDL-C showed a modest positive correlation with Lp(a) (r = 0.163, p = 0.040). Higher SYNTAX scores were associated with more extensive multivessel disease. Patients with ACS exhibited significantly higher Lp(a) and PCSK9 levels compared with healthy controls, but these biomarkers did not reflect angiographic disease complexity. Their role may lie more in underlying cardiovascular risk assessment than in predicting anatomical severity. Show less

Glaucoma is a leading cause of irreversible blindness worldwide. Current diagnostic methods often fail to detect disease at early stages. MicroRNAs (miRNAs), owing to their regulatory role in gene expression, have been investigated as potential biomarkers, although their diagnostic utility and clinical feasibility remain under evaluation. The aim of this work is to systematically review and synthesize evidence on the diagnostic significance of microRNAs and related genetic markers in glaucoma and its subtypes. A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including 16 studies with 17,300 participants. Odds ratios (ORs) and log ORs with 95% confidence intervals (CIs) were pooled using fixed-effects models. Subgroup analyses were performed by sample type, glaucoma subtype, and molecular pathway. Specific miRNAs (e.g., miR-143-3p, miR-182) were significantly associated with glaucoma (OR 6.32, 95% CI 5.31-7.54, p < 0.001). Stronger correlations were observed in aqueous humor samples (OR 13.79, 95% CI 6.81-27.94, p < 0.001). Dysregulation of miRNAs was linked to increased retinal ganglion cell apoptosis and altered aqueous humor osmolality. Genetic analysis showed that common alleles in ATOH7 (OR 1.55, 95% CI 1.40-1.72) and CDKN2B (OR 1.66, 95% CI 1.55-1.78) significantly increased glaucoma risk, while miR182 variants also showed strong associations. The autotaxin (ATX)-lysophosphatidic acid (LPA) pathway was consistently implicated (OR 3.94, 95% CI 2.46-6.32). MiRNAs, particularly in blood samples, show promise as feasible biomarkers for early glaucoma detection, while aqueous-humor-based testing remains clinically limited owing to invasiveness. Genetic variants such as ATOH7, CDKN2B, and miR182 modestly but consistently contribute to glaucoma susceptibility. Large-scale longitudinal studies are warranted to validate these findings and translate them into routine clinical practice. Show less

We aimed to identify key molecules that can moderately enhance the compensatory capacity of beta cells during obesity. Single-cell RNA-seq was used to profile the RNA expression of islet cells from diet-induced obese mice and pregnant mice. The gene and protein expression levels of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) were verified by quantitative PCR and immunofluorescence, respectively. The roles of ENPP2 were investigated using gain-of-function and loss-of-function approaches in Min6 beta cells, global Enpp2-knockout mice and beta cell Enpp2-overexpressing transgenic (Enpp2-Tg) mice. Using single-cell RNA-seq, we demonstrated that proliferation is the primary and common mechanism for compensating for beta cell numbers during both mouse obesity and pregnancy, with proliferation being more pronounced in pregnancy than in obesity. Additionally, many differentially expressed genes were co-regulated in both conditions. Among these, the pro-proliferative phosphodiesterase ENPP2 showed the highest increase in beta cells of pregnant mice and a moderate increase in beta cells of obese mice. Overexpression or knockdown of ENPP2 in Min6 beta cells revealed that ENPP2 promoted beta cell proliferation, inhibited apoptosis and enhanced high-glucose-stimulated insulin secretion. These effects of ENPP2 were further validated in vivo using Enpp2-Tg mice. In Enpp2-knockout mice fed a high-fat diet, the deficiency of ENPP2 resulted in insufficient compensation of beta cells during obesity. The pro-proliferative role of ENPP2 in beta cells was mediated through the lysophosphatidic acid (LPA)-Akt/mammalian target of rapamycin (mTOR) signalling pathway via LPA receptor 2. However, the expression of ENPP2 was reduced in the mouse model of diabetes and in human participants with type 2 diabetes compared with non-diabetic control groups. Furthermore, ENPP2 was co-upregulated by a synergy of oestradiol and progesterone. ENPP2 may serve as a key regulator in beta cell compensation during obesity, and modulating its levels in beta cells could be a potential therapeutic target for mitigating beta cell deterioration in diabetes. Show less

To investigate the moderating role of physical activity intensity and sedentary break patterns on the association between sedentary time (ST) and cardiometabolic risk in older adults. This cross-sectional study included 248 community-dwelling older adults without major cardiovascular diseases (66.0 ± 4.6 years; 78% female). Physical activity and ST were measured using a hip-worn accelerometer over seven consecutive days. Cardiometabolic disease risk was assessed using a sex-specific continuous metabolic syndrome score (cMetS). ST was entered as the explanatory variable for cMetS, while moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and the number of short (1-5 min) and long (>5 min) sedentary breaks were tested as moderators. All analyses were adjusted for traditional cardiometabolic risk factors and accelerometer wear time. MVPA (β = -0.005, p = 0.046), LPA (β = -0.030, p = 0.050), short (β = -0.003, p = 0.070) and long (β = -0.010, p = 0.011) sedentary breaks moderated the association between ST and cMetS. The Johnson-Neyman technique revealed that the association between ST and cMetS became non-significant (p ≥ 0.05) at thresholds of MVPA ≥ 19 min/day, LPA ≥ 5.9 h/day, short breaks ≥ 87/day, and long breaks ≥ 10/day. Our findings suggest that specific thresholds of MVPA and LPA, as well as short and long sedentary breaks may offset the deleterious association between ST and cardiometabolic risk in older adults. Show less

Single-stranded DNA (ssDNA) has extremely high design flexibility and specific functions. Therefore, ssDNA is used in crucial practical applications in many fields, such as molecular detection, gene editing, and nanotechnology. However, the existing methods for ssDNA preparation often present limitations in terms of yield, purity, and length applicability. In order to overcome these challenges, the present study proposes a ssDNA separation method that utilizes the modification of linear polyacrylamide (LPA) combined with denaturing agarose gel electrophoresis (DAGE). The method is referred to as LPA-DAGE. The underlying principle is to produce LPA-modified double-stranded DNA (dsDNA) through PCR using the LPA primer and then achieve efficient ssDNA separation using denaturing agarose gel electrophoresis based on molecular weight differences. This method can stably recover ssDNA showing significant advantages over the existing methods in terms of purity and recovery rate. The results of this study demonstrate that the proposed ssDNA preparation method enables signal amplification using fluorescence Show less

Preschool children's activity patterns differ between weekdays and weekends. Weekdays are constrained by structured educational activities and parental commitments, which limit flexibility, while weekends provide opportunities for extra sleep (SLP), physical activity (PA), and reduced sedentary behavior (SB). This study aims to estimate optimal activity durations for both weekdays and weekends, based on the development of executive function (EF), fundamental movement skills (FMS), and physical fitness (PF) in preschool children. A total of 289 preschool children aged 3-6 years from four kindergartens in Zhejiang Province participated. PA and SLP were objectively measured using accelerometers and the Children's Sleep Quality Questionnaire. EF, which includes working memory, inhibitory control, and cognitive flexibility, was measured using the Early Years Toolbox (EYT). FMS were assessed using the test of gross motor development-3rd edition (TGMD-3), and PF was evaluated according to the National Physical Fitness Measurement Manual (Preschool Children Section). Compositional data regression models were applied to examine the relationship between 24-h movement behaviors and health outcomes on weekdays and weekends. Optimal time-use compositions for each outcome were estimated, and 3D quaternary plots were generated to define the Goldilocks Day at the center of the overlapping regions. 24-h movement behaviors were significantly correlated with EF (weekdays: F = 5.4, This study provides recommendations for time allocation on weekdays and weekends to support the healthy development of preschool children. Show less

Internalizing and externalizing behavior problems co-occur frequently and there is heterogeneity in the co-occurrence of such symptoms; however, few studies have explored this heterogeneity and its developmental mechanisms from a person-centered perspective. The primary aim of this study is to employ Latent Profile Analysis (LPA) and Latent Transition Analysis (LTA)-person-centered statistical approaches-to explore this underlying heterogeneity, uncover its dynamic developmental trajectories, and further examine the key factors that influence class membership and transitions. A sample of 2232 Chinese college students from three universities in Chongqing was assessed at two time points spaced ten months apart. Latent Profile Analysis (LPA) and Latent Transition Analysis (LTA) were conducted on measures of internalizing and externalizing problems. LPA revealed three distinct profiles for both internalizing problems ("Low-Risk/Well-Adapted", "Moderate-Risk/Affective-Distress", "High-Risk/Comorbid") and externalizing problems ("Well-Adapted", "Adaptation Difficulties", "Maladaptive") at T1, with similar structures at T2. LTA indicated high stability for the low- and high-risk internalizing profiles, but significant fluidity in the middle, with nearly half of the moderate-risk group transitioning to the high-risk profile. For externalizing problems, there was a pronounced shift toward the "Maladaptive" profile over time. Negative parental rearing and PWU were significant risk factors for adverse transitions, while positive parenting, self-transcendence values, and objective social support served as protective factors. Co-occurring internalizing and externalizing problems among Chinese college students are heterogeneous and dynamic. The moderate-risk group represents a critical target for early intervention. Modifiable ecological factors across family, individual, and technological domains significantly predict longitudinal trajectories, informing targeted prevention strategies. Show less

Extensive research has documented a high comorbidity prevalence between depression and Internet gaming disorder (IGD). However, the distinct comorbidity patterns in adolescents have not been thoroughly investigated. Additionally, the longitudinal dynamics of these comorbidity patterns over time and the specific factors that may drive these transitions remain poorly understood. A total of 3,296 adolescents (1,501 boys; age baseline: 15.17 [1.44] years) were included in the current study. Latent profile analysis (LPA) was used to identify optimal comorbidity patterns of depression and IGD, while random intercept latent transition analysis (RI-LTA) was conducted to assess transitions in the comorbidity patterns over one and a half years and to identify factors influencing these transitions. Three patterns of comorbidity between depression and IGD symptoms were identified: no symptoms, low depression-high IGD symptoms, and high depression-low IGD symptoms. Results indicate that 72 % of individuals exhibited a stable symptom pattern trajectory. From Time 1 to Time 2, the probabilities of remaining in the three patterns were 78.3 %, 31.5 %, and 51.5 %, respectively. Findings also showed that sex, grade levels, boarding status, father's occupation as well as educational attainment, intra-week and weekend screen time, parent-child relationship, and perceived social support influenced the probabilities of transitions between comorbidity patterns in adolescents over time. Adopting targeted interventions for different comorbidity patterns and transitions, while considering specific influencing factors, provides insights into adolescent mental health dynamics and inform more effective prevention and support strategies. Show less

Direct oral anticoagulants, including rivaroxaban, are widely prescribed for the prevention and treatment of thromboembolic disorders. Despite generally predictable pharmacokinetics (PK), real-world data reveal striking interindividual variability in exposure, raising concerns for both efficacy and bleeding risk. Known genetic and clinical determinants explain only part of this variability, underscoring the need to identify additional contributors. This study aimed to explore systemic protein signatures associated with rivaroxaban exposure intensity. Plasma samples were obtained from 64 participants in a phase I clinical study (NCT04180436) including healthy controls, obese patients, and post-bariatric surgery patients. Rivaroxaban PK was assessed after 20 mg once-daily dosing, and patients were stratified into high and low exposure groups. Untargeted plasma proteomic analysis was performed by liquid chromatography coupled with high-resolution mass spectrometry, followed by univariate and multivariate statistical analyses. Targeted C-reactive protein (CRP) quantification and multiplex cytokine assays were used to validate findings. Differential abundance and multivariate modeling identified inflammation and vascular related proteins associated with high rivaroxaban exposure. Notably, CRP and lipoprotein(a) (LPA) were consistently elevated in high exposure groups. Targeted CRP quantification confirmed these results, even in cases of mild to moderate inflammation. Cytokine analyses revealed a pro-inflammatory profile, characterized by increased interferon gamma and reduced Tumor Necrosis Factor alpha in high exposure patients. Protein-protein interaction networks highlighted CRP, LPA, albumin, and Apolipoprotein B as central hubs, while functional enrichment revealed pathways related to acute inflammation, oxidative stress, and vascular regulation. These findings suggest that systemic inflammation may contribute to rivaroxaban overexposure, with CRP emerging as a promising biomarker to support more personalized anticoagulant strategies. Show less

Research has shown that compulsive sexual behavior disorder (CSBD) and problematic pornography use (PPU) are associated with mental disorders. However, less is known about how trajectories of probable CSBD and PPU prospectively contribute to the evolvement of psychopathology during a stressful period. In this study, we applied latent profile analysis (LPA) to identify distinct latent profiles of participants' probable CSBD and PPU across 2018 and 2022, prior to the October 2023 attack in Israel (Iron Swords War), and to examine how these profiles prospectively predict the evolvement of psychopathology during wartime. A longitudinal study surveying the in a community sample of Jewish population in Israel, aged 18-70, was conducted before October 7th 2023 attack and during the subsequent war. Participants completed self-report measures of probable CSBD and PPU, psychopathology (global distress, emotional dysregulation, PTSD, anxiety, depression), and level and kind of exposure to the October 7th attack. LPA revealed four distinct probable CSBD/PPU profiles during the two pre-war waves: 'no disorder' (n = 952; 80.54 %),'recovery' (n = 138; 11.68 %),'delayed onset' (n = 50; 4.23 %), and 'chronic' (n = 42; 3.55 %). Using T3 and T4 for the trajectory results, the no-disorder group consistently demonstrated the lowest levels of psychopathology and out-of-control behaviors during wartime, while the chronic group reported significantly higher distress; differential impacts among probable CSBD/PPU trajectory groups showed that the no-disorder group reported decreasing anxiety and depression during wartime in contrast to the chronic group that experienced increased PTSD severity. This research offers a nuanced understanding of probable CSBD/PPU profiles, showing how these profiles impact the evolvement of psychopathology during wartime. Show less

Lipoprotein (a) [Lp (a)] may confer pro-thrombotic potential, and high concentrations may be an independent risk for MI. This systematic review sought to investigate the association of Lp (a) levels with post-revascularization Major Adverse Cardiac Events (MACE) in patients with CAD, ACS, and DM. A systematic literature search for original investigations was performed using PubMed/MEDLINE, Embase, Scopus, and Google Scholar, searching for articles (meeting inclusion criteria) focusing on the relationship between Lp(a), DM, and PCI in patients with ACS, MI, or IHD and the impact on cardiovascular outcomes. The data was abstracted and descriptively summarized. The systematic review selected four relevant articles: 3 prospective Konishi et al., (2016); Silverio et al., (2022); and Li et al., (2023) and one retrospective (Takahashi et al., 2020). Total population: 4624, total males: 3719. Konishi et al. (2016) concluded that an elevated Lp(a) is an independent risk factor for cardiac death and/or ACS recurrence in diabetics undergoing PCI. The adjusted OR for cardiac death and ACS in the high Lp(a) group vs. the low Lp(a) group was 1.20 (CI 1.00-1.42), p = 0.04. Takahashi et al. (2020) showed that after adjusting for clinical covariates, high Lp(a) was independently associated with a higher frequency of MACE and poorer long-term outcomes compared to low Lp(a). The adjusted OR for the risk of MACE in patients with high Lp (a) vs. low Lp (a) was 1.83 (CI 1.16-2.95), p = 0.009. Silverio et al. (2022) showed that while there was an increased risk of recurrent MI in this patient population without DM, it was not confirmed in patients with DM. Compared with the lowest Lp (a) category, non-DM patients with very high Lp (a) >70 mg/dl vs. low Lp (a) showed a higher risk of recurrent MI and all-cause death; adjusted OR 2.839 (CI 1.382-5.832), p = 0.005. In diabetics, high Lp (a) vs. low Lp (a) = 1.115 (CI 0.405-3.071), p = 0.833. There is some evidence that Lp (a) levels are an independent risk factor for MACE in patients who underwent PCI for CAD. There is also some evidence that elevated Lp (a) levels are associated with a worse prognosis in patients with DM after PCI, but this association is not consistent in the literature. Further prospective multicenter studies are required in order to elucidate this association. Show less

Families with children diagnosed with autism spectrum disorder (ASD) often encounter significant challenges, manifesting in elevated stress levels and compromised physical and mental well-being. This study employed Latent Profile Analysis (LPA) to comprehensively examine family resilience attributes among 328 Chinese parents of children with ASD. Drawing on Walsh's family resilience framework and the Double ABCX stress-adaptation model, the research examined how protective factors (social support, posttraumatic growth) and risk factors (family stressors) distinctively characterize resilience profiles and predict profile membership, alongside sociodemographic correlates. Through rigorous statistical analysis, the following three distinct family resilience profiles emerged: adversity (32.31%; characterized by low resilience), ordinary (46.65%; demonstrating moderate resilience) and growth (21.03%; exhibiting high resilience). Critically, the findings revealed that higher family income, perceived social support and posttraumatic growth were associated with higher family resilience, while family stressors were associated with lower family resilience. These insights underscore the importance of developing targeted, personalized intervention strategies that can effectively enhance familial coping mechanisms and psychological adaptation for families navigating the complex challenges of ASD. Show less

Lysophosphatidic acid (LPA) is a crucial bioactive lipid mediator involved in various physiological processes; however, its role in macrophage polarization remains poorly understood; therefore, this study aimed to elucidate the modulatory effect of LPA on macrophage polarization, particularly its ability to shift M1 macrophages towards an M2-like phenotype, using murine macrophage RAW264.7 cells to confirm the expression of LPA receptor 1 (LPAR1) through immunofluorescence staining, which revealed that treatment of resting MO macrophages with LPA decreased inflammatory cytokines (IL-6, TNF-α) and increased TGF-β, with similar effects observed in LPS-stimulated cells and reversed by the LPAR1 inhibitor AM095, and immunostaining demonstrated a notable shift from an M1- to M2-like phenotype, as evidenced by an increase in the arginase-1/CD68 ratio; furthermore, LPA significantly decreased lactate production and increased ATP production in M1 macrophages, promoting a shift towards oxidative phosphorylation and suggesting metabolic reprogramming towards an M2-like phenotype, significantly influencing macrophage polarization and promoting a shift from a pro-inflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype; these results suggest that treatment with LPA may help ameliorate diseases characterized by aberrant macrophage polarization, providing insights for the development of potential therapeutic strategies for inflammatory and autoimmune diseases. Show less

To examine the association of types and intensities of physical activity (PA) and depression with all-cause mortality in a population-based cohort of older adults, where evidence is scarce or inconsistent. We analysed data from 2060 and 3263 older adults (70.5 ± 5.5 years; 2800 women) participating in the Seniors-ENRICA 1 and 2 cohorts, respectively. Time spent in walking, gardening, do-it-yourself (DIY) activities, housework, cycling, and sports was self-reported using the EPIC questionnaire. PA was categorized by intensity as follows: light (LPA; walking+housework), moderate (MPA; gardening+DIY), and vigorous PA (VPA; cycling+sports); in addition, moderate-to-vigorous (MVPA) and total PA were computed. Depression was measured using the Geriatric Depression Scale (GDS-10) score ≥ 3. All-cause mortality was ascertained up to January 31, 2024. Multivariable regression models were used to examine associations, adjusting for key confounders. Inverse associations were observed between all types and intensities of PA and both depression at baseline, except for cycling. In participants with depression, time spent in housework, sports, LPA, VPA, and total PA was similarly associated with reduced mortality risk. Meeting MVPA recommendations was associated with a 20 % and 32 % lower mortality in individuals without and with depression, respectively. In dose-response analyses, participants with depression who engaged in the same volume of PA as those without depression experienced a greater reduction in mortality risk. PA was associated with lower odds of prevalent depression in older adults. Notably, older adults with depression experienced greater mortality benefits from comparable levels of physical activity than those without depression. Show less

The genetic influences on normal aortic valve function and their impact on aortic stenosis risk are of substantial interest. We used deep learning to measure peak velocity, mean gradient and aortic valve area from magnetic resonance imaging and conducted genome-wide association studies (GWAS) in 59,571 participants in the UK Biobank. Incorporating the aortic valve measurement GWAS with aortic stenosis GWAS using multitrait analysis of GWAS (MTAG), we identified 166 distinct loci (134 with aortic valve traits, 134 with aortic stenosis and 166 unique loci across all GWAS), including PCSK9 and LDLR. The MTAG aortic stenosis PGS was associated with aortic stenosis in All of Us (hazard ratio (HR) = 3.32 for top 5% versus all others, P = 8.8 × 10 Show less

Lysophosphatidic acid (LPA) and its receptor LPA1 have been implicated in tissue inflammation and fibrosis; however, their role in mucus overproduction remains unclear. Pulmonary neuroendocrine cells (PNECs), which are rare airway epithelial cells, contribute to mucus overproduction and immune modulation. In this study, we investigated the role of the LPA/LPA1 receptor axis in goblet cell hyperplasia and mucus overproduction, as well as the contribution of PNECs, using a chronic mouse model of bronchial asthma. A chronic mouse model of asthma was established by sensitization and challenge with the house dust mite antigen Dermatophagoides pteronyssinus (Dp), with or without treatment using the LPA1 antagonist AM095. Airway hyperresponsiveness, histopathology, mediator concentrations, and molecular expression in lung homogenate supernatants were evaluated. Lysophospholipid levels and low-molecular-weight metabolites were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lung LPA 22:5 levels were elevated in Dp-challenged mice. LPA1 receptors were co-localized with PNECs in the lung. Treatment with AM095 reduced goblet cell hyperplasia by inhibiting the production of gamma-aminobutyric acid (GABA) and calcitonin gene-related peptide (CGRP) by PNECs. It also suppressed arginase 1 and polyamine production in CGRP-stimulated M2 macrophages. AM095 did not affect eosinophil extracellular trap (EET) formation in bronchoalveolar lavage fluid, which activates PNECs. The LPA/LPA1 axis promotes goblet cell hyperplasia through PNEC activation and downstream GABA and CGRP signaling in a chronic asthma model. LPA1 antagonism may represent a potential therapeutic strategy for controlling mucus overproduction in asthma. Show less

Colorectal cancer is the third leading cause of cancer-related deaths worldwide. Aberrant canonical Wnt signaling is a hallmark of this cancer type. It has been reported that LPA is a bioactive lipid that plays different roles in colon cancer by activating its G-protein-coupled receptors, promoting cell proliferation, migration, survival, and angiogenesis. Although it has been reported that LPA activates canonical Wnt signaling, the mechanisms underlying their interaction remain unclear; this study aims to investigate them. As previously reported, LPA receptor expression changes under malignant conditions: while LPA Show less

Physical activity (PA), sedentary behavior (SB), and sleep independently influence cardiometabolic health in youth. Because these behaviors are interdependent within a 24-hour day, compositional data analysis has emerged as a method to examine how the distribution of time across behaviors relates to health. While evidence exists for adults and preschool-aged children, findings for school-aged youth, who are at higher risk for inactivity, remain limited. This systematic review examined associations between light PA (LPA), moderate-to-vigorous PA (MVPA), SB, and sleep and cardiometabolic health among youth aged 6 to 17 years. In May 2024, two reviewers conducted systematic searches across five databases following Cochrane criteria. Eligible studies were peer reviewed, included youth aged 6 to 17 years, and used compositional data analysis to assess cardiometabolic outcomes. Of 1,021 records screened, 10 studies met inclusion criteria, and 9 were rated moderate or high quality. MVPA, particularly vigorous PA, showed the most consistent benefits, including lower adiposity, reduced cardiometabolic risk, and higher fitness. SB was generally associated with adverse outcomes, while findings for LPA and sleep were mixed or null. Overall, evidence suggests that daily movement behavior distributions are important predictors of cardiometabolic health in youth and support movement-based public health guidance. Show less

Lipoprotein(a) [Lp(a)] is a novel biomarker for Atherosclerotic cardiovascular disease prediction. Yet, given the scarcity in high-quality evidence, its use in routine primary prevention screening is lacking. For this reason, we aimed to assess Lp(a) prognostic utility during routine screening. A retrospective cohort of adults with available Lp(a) measurement, taken during a screening program (2008-2024) in a tertiary care center. Major adverse cardiovascular events (MACE) was the study primary outcome. The optimal Lp(a) threshold was evaluated using spline curve analysis and validated by Cox regression models adjusted for clinical and laboratory covariates. Subgroup analyses were performed in patients with SCORE2 and PCE data. 3052 people were included with a median (IQR) follow-up of 6.4 (3.5-12) years. Lp(a) threshold of 50 mg/dL was identified as a risk inflection point. High Lp(a) (> 50 mg/dL) was associated with increased MACE risk, independent of clinical data (HR 1.55, 95% CI 1.10-2.17, p = 0.011) or different laboratory variables (HR 1.62, 95% CI 1.07-2.46). High Lp(a) remained a predictor for MACE in models incorporating the SCORE2 and PCE scores, and its incorporation into these scores improved their performance in high-risk patients. In people with cardiovascular comorbidities, the optimal Lp(a) threshold for MACE prediction was 61 mg/dL, while it was 48.4 mg/dL in those without (n = 2778). In a large ambulatory and mostly healthy cohort, Lp(a) showed a strong predictive utility for cardiovascular events. These findings support the integration of Lp(a) into primary cardiovascular risk assessment and role in guiding emerging targeted therapies. Show less