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Executive function (EF) deficits are a core cognitive feature of autism spectrum disorder (ASD) and are closely associated with social responsiveness. Previous research has primarily focused on children with ASD, whereas how specific executive components relate to social functioning in adults remains less clear. This study examined whether patterns of association between EF and social responsiveness differ between children and adults with and without ASD. Data were obtained from the Autism Brain Imaging Data Exchange II (ABIDE II), including 423 participants aged 8-23 years (ASD = 184; controls = 239). EF was evaluated using the Behavior Rating Inventory of Executive Function (BRIEF/BRIEF-A), and social responsiveness was assessed with the Social Responsiveness Scale (SRS). Covariates of age, sex, and full-scale IQ (FIQ) were controlled using entropy balancing in children and multiple regression in adults. Hierarchical regression, moderated mediation analysis, and latent profile analysis (LPA) were conducted to examine the moderation, mediation, and heterogeneity effects, respectively. Across both child and adult samples, individuals with ASD exhibited significantly higher T-scores than controls on nearly all BRIEF and SRS subdomains after covariate adjustment (all adjusted p < 0.01), indicating widespread EF and social responsiveness impairments. Moderation analyses revealed no significant age group × EF interaction, indicating that the association between EF and social responsiveness was consistent across development. Mediation analysis revealed age-specific pathways, with EF broadly mediating social responsiveness in adults but showing more selective mediation in children. LPA identified four distinct subtypes, which were independent of age, sex, and FIQ. EF-social responsiveness associations were evident across development, but the functional contribution of specific executive components became more differentiated with age. Working memory showed greater relative prominence in adulthood. Latent profile analysis revealed heterogeneity in how executive difficulties align with social challenges, supporting developmentally informed assessment and clinical interpretation rather than direct treatment recommendations. Show less

Phosphatidic acid (PA) is increasingly recognized as an important endogenous regulator of cell proliferation and migration, playing relevant roles in physiology and pathology. However, the potential and prominence of extracellular PA in controlling cell functions are not so well established. The present review article has been undertaken to update and discuss the latest findings on extracellular PA as regulator of cell homeostasis, with special attention being paid to its role in the regulation of cell growth and migration. Specifically, exogenous PA potently stimulates myoblast proliferation and lung cancer cell migration, pointing to a critical role of this glycerophospholipid in the regulation of muscle cell regeneration and lung cancer dissemination. Interestingly, both of these actions are mediated through interaction of PA with lysophosphatidic acid (LPA) receptors and the subsequent activation of different signal transduction pathways. In particular, PA induces mitogen-activated protein kinase kinase (MEK)/extracellularly regulated kinases (ERK) 1 and 2, phosphatidylinositol 3-kinase (PI3K)/Akt, focal adhesion kinase (FAK)/Rac1, and Janus kinase-2 (JAK2)/signal transducer and activator of transcription 3 (STAT3). These findings may contribute to a better understanding of muscle cell biology and may help to develop new therapeutic strategies to treat lung cancer dissemination. Show less

Hemolytic disease of the fetus and newborn (HDFN) is a potentially life-threatening condition caused by maternal alloimmunization against fetal red blood cell (RBC) antigens. While most cases involve well-characterized antibodies such as anti-D, anti-c, or anti-K, antibodies against low-prevalence antigens (LPAs) - particularly those within the MNS blood group system - remain underrecognized and underreported. We report a case of maternal alloimmunization against the paternally inherited LPA MUT (MNS35), carried on a hybrid glycophorin ( This case supports the pathogenicity of anti-MUT as a cause of severe HDFN. It underscores the diagnostic challenges posed by antibodies against LPAs and highlights the importance of extended serological, molecular, and functional testing. Crossmatching maternal plasma with paternal RBCs and systematic evaluation of serological discrepancies can reveal otherwise undetectable alloantibodies. Early identification, functional assessment, and multidisciplinary management are key to optimizing outcomes in pregnancies complicated by rare RBC alloimmunization. Anti-MUT should be considered a clinically significant antibody with the potential to cause severe HDFN, warranting proactive perinatal surveillance. Show less

The effects of extruded flaxseed-pulse mixture (LinPRO-24) on growth performance, tissue fatty acid composition, carcass traits, and meat quality in broilers were investigated. A total of 540-day-old male 308 Ross chicks were placed in pens (30 chicks/pen) and allocated to three diets (n = 6) in a completely randomized design. The diets were: CON (basal corn-soybean meal diet); LPA (CON+2.5% LinPRO-24); and LPB (CON+ 5.0% LinPRO-24). Diets were isocaloric and isonitrogenous, formulated for starter (day 1-10), grower (day 11-24), and finisher (day 24-34). Feed intake and body weight (BW) were recorded daily, and mortalities as they occurred to calculate average daily gain (AWG) and FCR. On day 34, visceral organs, breast tissue, and leg tissue were sampled. The CON group exhibited higher overall BW, AWG, and AFI than LPB (P < 0.05). Breast and leg tissues of birds fed LPB had the highest concentration of Alpha-linolenic acid (ALA) and total ω-3 PUFA followed by LPA; both had a higher ALA concentration than the CON group (P < 0.05). Thus, the ω-6:ω-3 ratio in these tissues was lower for LPA and LPB groups (P < 0.05). Additionally, both LPA and LPB groups had lower Docosatetraenoic acid (DTA, C22:4 ω-6), higher Docosapentaenoic acid (DPA, C22:5 ω-3) and total PUFA content, resulting in a reduced SFA:PUFA ratio in leg tissue compared with the CON group (P < 0.05). However, LPB negatively affected the water-holding capacity (WHC) in breast meat compared with the CON and in leg tissue compared with LPA treatment (P < 0.05). Moreover, LPB increased muscle hardness and gumminess in the breast compared with the CON group (P < 0.05), thereby negatively affecting meat textural qualities. Overall, both LPA and LPB diets increased the ω-3 PUFA content in poultry meat, thereby reducing the ω-6:ω-3 ratio. However, the current study suggests that the use of LinPRO-24 at 2.5% may be more appropriate for improving the fatty acid profile of broiler meat without compromising production performance and meat quality. Show less

Accurate classification of intestinal polyps is crucial for preventing colorectal cancer but is hindered by visual similarity among subtypes and endoscopic variability. While deep learning aids in diagnosis, single-modal models face efficiency-accuracy trade-offs and ignore pathological semantics. We propose a multimodal framework that integrates endoscopic images with structured pathological descriptions to bridge this gap. We propose LPA-Tuning CLIP, which incorporates three key innovations: replacing CLIP's instance-level contrastive loss with cross-modal projection matching (CMPM) with ID loss to explicitly optimize intraclass compactness and interclass separation through label-aware image-text similarity matrices; introducing structured clinical semantic templates that encode WHO diagnostic criteria into hierarchical text prompts for consistent pathology annotations; and developing medical-aware augmentation that preserves lesion features while reducing domain shifts. The experimental results demonstrate that our proposed method achieves an accuracy of 85.8% and an F1 score of 0.862 on the internal test set, establishing a new state-of-the-art performance for intestinal polyp classification. This study proposes a multimodal polyp classification paradigm that achieves 85.8% accuracy on three-subtype classification via endoscopic image-pathology text joint representation learning, outperforming unimodal baselines by 8.7% and a multimodal baseline by 4.3%. Show less

The quality of informal care for people with dementia (PwD) has gained increasing importance, as most PwD prefer home-based care over institutional placement. However, evidence-based intervention programs tailored to distinct care quality profiles remain limited. Additionally, the absence of clear thresholds to identify PwD receiving low-quality informal care poses a challenge for research and clinical practice. Thus, this study aimed to identify the profiles of quality of care (QoC) among informal caregivers of PwD, explore influencing factors of different profile, and determine the optimal cut-off score of the Exemplary Care Scale (ECS). A cross-sectional survey was conducted. A total of 213 dyads of PwD and their informal caregivers were recruited from memory clinic, rehabilitation clinic, and neurological clinic of a tertiary hospitals and communities in Wuhan, Hubei, China, between July 15, 2023, and July 14, 2024. Latent profile analysis (LPA) was employed to identify QoC profiles. Multinomial logistic regression was performed to explore influencing factors of profile membership. Receiver Operating Characteristic (ROC) analysis was conducted to determine the ECS cut-off score. Three distinct QoC profiles were identified: high (24.41%), moderate (44.60%), and low (30.99%). Among informal caregivers, lower monthly income, insufficient social support, and higher perceived overload were associated with low QoC profile, whereas, better quality of pre-illness relationship with PwD and greater activities of daily living (ADL) of PwD were associated with high QoC. ROC analysis yielded an optimal ECS cut‑off score of 15, with high sensitivity (0.993) and specificity (0.955). This study identified three distinct QoC profiles among caregivers of PwD, underscoring the heterogeneity of informal care quality. The identified predictors and the validated ECS cut‑off score of 15 provide an empirical basis for developing tailored screening tools and targeted interventions for high‑risk caregiver subgroups. Show less

Menopause may coincide with rising Lp(a) levels, a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Characterizing changes in Lp(a) across menopause may inform risk stratification and testing recommendations. . We examined changes in serum Lp(a) levels by menopausal status among women with Lp(a) measured at visits 1 and 2 in the UK Biobank. Lp(a) analyses were examined by menopausal status: those who underwent menopause (N=415), those who remained premenopausal (N=532), and those who remained postmenopausal (N=3,615) between visits. We examined the change in Lp(a) between visits stratified by visit 1 Lp(a) levels. The primary outcome was incident Lp(a) ≥125 nmol/L at visit 2, estimated using Poisson regression with adjustment for baseline age. Data were available for 4,562 women (mean age at visit 1 = 57±7 years; median Lp(a) at visit 1 = 22 (IQR: 47) nmol/L; median time between visits = 4 (IQR: 1) years). At visit 1, median Lp(a) was slightly higher in postmenopausal women (23 nmol/L) than premenopausal women (19 nmol/L). Overall, median changes in Lp(a) between visits 1 and 2 were modest. Among women with intermediate visit 1 Lp(a) levels (75-125 nmol/L), those who transitioned through menopause experienced a median increase of 34.9 (-6.7, 53.0) nmol/L between visits, an approximately fourfold greater increase than for women who remained pre- (7.9 nmol/L) or postmenopausal (8.0 nmol/L). Further, 56% of women with intermediate visit 1 Lp(a) levels who transitioned through menopause between visits had incident Lp(a) ≥125 nmol/L at visit 2, compared with 29% and 28% of women who remained pre- or postmenopausal, representing an age-adjusted risk ratio of 2.26 (95% CI: 1.31, 3.90). Relying on a single lifetime Lp(a) measurement may miss clinically relevant increases during menopause. Repeat testing in women as they age may improve identification of those at high risk for ASCVD. Show less

This study aimed to explore the association between serum lipoprotein(a) [Lp(a)] levels and recurrent acute coronary syndrome (ACS) and revascularization of target lesions in patients with ACS who showed no functional ischemia on fractional flow reserve (FFR) testing during coronary angiography (CAG). The retrospective observational study was conducted at the General Hospital of Northern Theater Command and included 513 patients with new ACS recruited from 23 February 2016 to 6 November 2023 and followed up. These patients underwent CAG examination and were found to have at least one coronary artery with moderate or greater stenosis, and also underwent FFR measurement with FFR value >0.80. Patients experienced recurrent ACS and underwent unplanned revascularization were defined as the revascularization group, while patients did not experience recurrent ACS and undergo unplanned revascularization were assigned to the no revascularization group. The study employed propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis to evaluate the correlation between serum Lp(a) and recurrent ACS and unplanned revascularization in target lesion with FFR value >0.80. Serum Lp(a) levels were higher in female patients. There were no statistically significant differences in the basic clinical characteristics, medication use, laboratory test results or ejection fraction values between the two groups. During a average follow-up of 6.5 years, 119 patients (23.2%) experienced recurrent ACS and unplanned revascularization in the target lesion. The level of serum Lp(a) in the patients that underwent unplanned revascularization was significantly higher than in the group that did not undergo repeated revascularization (65.80 mmol/L vs. 60.57 mmol/L, Serum Lp(a) is an independent risk factor for recurrent ACS and unplanned revascularization in patients with ACS and FFR negative plaque. Show less

Lipidomic analysis enables the detailed characterization of platelet concentrates from donors of different ages, offering valuable insights into the role of lipid mediators in aging and transfusion-related adverse reactions (AR). In this study, we analyzed lipidomic profiles from a cohort of single-donor apheresis platelet concentrates, classified into three age groups: 20-44, 45-59, and 60-70 years. Total levels of LPC, LPA, S1P, and eicosanoids did not exhibit significant age-related changes. However, LPA 18:1, LPC 18:1, and S1P levels decreased with advancing age. When examining the relationship between different age groups and their association with AR, we found that LPA, LPC, and eicosanoids are associated with AR in an age-dependent manner. Based on these findings, we investigated the effect of age-related levels of LPA, LPC, and S1P on platelet and endothelial cell biology. These lipid mediators were found to modulate platelet activation, as demonstrated by increased expression of P-selectin, phosphatidylserine, platelet aggregation, as well as endothelial activation, marked by elevated expression of ICAM-1, VCAM-1, and CD40. Our findings present a comprehensive lipidomic profile of single-donor apheresis platelet concentrates across various age groups, highlighting several lipid mediators that may be implicated in aging and AR. Show less

Hodgkin lymphoma (HL) is one of the most common cancers during adolescence. Advances in treatment have achieved survival rates exceeding 90%. However, long-term treatment-related sequelae, including cardiovascular disease and metabolic syndrome, significantly affect the quality of life of survivors. Physical activity (PA) is considered a key strategy to mitigate these risks. Current studies predominantly rely on subjective assessments of movement behavior, which may lack accuracy. This cross-sectional study aims to use device-based monitoring to characterize levels of sedentary behavior and physical activity in survivors of childhood-diagnosed HL. Specific objectives were to evaluate these behaviors across age and gender groups and to assess compliance with physical activity guidelines for the adult population. The study involved 51 participants (59% female), with a median age of 25 years, a median age at diagnosis of 16 years, and a median time since diagnosis of 11 years. PA and sedentary behavior (SB) were measured over seven days using the Axivity AX3 accelerometer with a 24-hour wear protocol. Movement behavior was categorized into SB, light PA (LPA), moderate PA (MPA), and vigorous PA (VPA). Group differences in movement behaviors were examined using non-parametric tests, and results are presented as medians with interquartile ranges. Participants had a median daily time of 704.8 min in SB (IQR 127.9), 181.2 min in LPA (IQR 81.3), 110.2 min in MPA (IQR 68.8), and 2.8 min in VPA (IQR 2.8). Combined moderate-to-vigorous physical activity (MVPA) accounted for a median of 115 min per day (IQR 69.8). Significant differences in LPA were observed: men spent less time in LPA compared to women (p = 0.032), and younger participants spent less time in LPA compared to older participants (p = 0.006). While 100% of participants met the WHO-recommended threshold of > 150 min of MPA per week, only 14% met the guideline of > 75 min of VPA per week. Our study indicates that survivors diagnosed with childhood HL can achieve the levels of MVPA recommended by current adult PA guidelines, despite undergoing chemotherapy and radiotherapy. Additionally, significant differences in low-intensity PA were identified: men and younger participants spent less time in LPA compared to women and older participants, respectively. These findings highlight the importance of monitoring movement behaviors in long-term follow-up care to identify survivors with insufficient physical activity and excessive sedentary behavior and to implement targeted interventions to reduce long-term cardiovascular and metabolic risk. Given the cross-sectional design, causal relationships and changes in physical activity behavior over time cannot be inferred. Show less

Tetralogy of Fallot with pulmonary atresia (ToF-PA) requires precise delineation of extracardiac pulmonary blood supply to guide optimal palliation, especially in duct-dependent physiology. We report an 8-month-old infant with late-onset central cyanosis and recurrent cry-triggered hyper cyanotic spells. Computed tomography (CT) thoracic angiography showed classic ToF with short-segment pulmonary atresia, a malaligned perimembranous ventricular septal defect, and hypoplastic yet confluent branch pulmonary arteries. A long, tortuous patent ductus arteriosus (PDA) provided dominant pulmonary flow, with severe focal juxtaductal stenosis just before insertion into the left pulmonary artery and reduced distal pulmonary arborization. A small ostium secundum atrial septal defect was identified. Minor systemic collaterals were seen, without large dominant major aortopulmonary collateral arteries, suggesting duct-dominant physiology potentially amenable to pulmonary artery rehabilitation. This case highlights late deterioration from progressive PDA-left pulmonary artery narrowing and underscores CT angiography as a key decision map for catheter or surgical palliation and operative planning. Show less

How schoolchildren distribute their time between movement behaviours may be impacted by the neighbourhood environment. Few studies have investigated the associations between the physical and social environment and the full movement behaviour composition, including times spent in moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behaviour, and sleep, and their findings are inconsistent. Therefore, our aim was to investigate this association in a large, national-representative sample of schoolchildren from major cities and regional/remote areas. We used data from the Longitudinal Study of Australian Children and the Child Health CheckPoint study, collected among 1230 child-parent pairs (child age range: 10–12 years). Parents were asked about neighbourhood general safety, access to destinations and services, and social capital and cohesion. Children’s time spent in MVPA, LPA, sedentary behaviour, and sleep was assessed using wrist-worn GENEActiv accelerometers. The associations between the physical and social environment characteristics (independent variables) and movement behaviour composition expressed as isometric log ratio coordinates (dependent variables) were examined using multiple linear regression analyses, adjusted for age, body mass index, pubertal status, sex, and socioeconomic position. Among schoolchildren from regional/remote areas, access to destinations and services (Pillai’s trace = 0.030; These findings highlight the importance of access to destinations and services, as well as social capital and cohesion, in shaping the movement behaviour composition among schoolchildren from regional/remote areas. More research is needed to draw conclusions about the association between neighbourhood environment and movement behaviour composition among schoolchildren from major cities. The online version contains supplementary material available at 10.1186/s12966-026-01879-z. Show less

Psychological maltreatment (PM) is a multidimensional construct that includes both cognitive and emotional aspects of maltreatment. It has devastating effects on individuals, which differ from one person to another. Utilizing latent profile analysis (LPA) facilitates exploring interactions among latent subgroups. However, few studies have investigated this construct using a person-centered approach. Therefore, in the present study, we conceptualized a multidimensional construct and utilized LPA that includes PM, emotional problems (i.e., depression, anxiety, negative self-concept, somatization, and hostility), and emotion dysregulation as profile indicators. Furthermore, the cognitive aspect of the sub-classes was predicted through cognitive flexibility. Data were gathered from 523 adolescents aged 14- 17 ( The findings indicate that five distinct latent profiles have emerged: Profile 1 “ Research based on mixture modeling approaches offers a supplementary perspective to the existing literature on psychopathology. The findings may help practitioners identify victims of psychological maltreatment through cognitive flexibility and significantly enhance the development of intervention strategies based on their profile types. Show less

The brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroprotection, and we have previously demonstrated BDNF-mediated neuroprotective effects in mesenchymal stromal cells (MSCs). The present study aimed to investigate whether BDNF-overexpressing MSCs enhance the therapeutic efficacy of naïve MSCs in a preclinical model of severe neonatal intraventricular hemorrhage (IVH). We exposed primary rat neuronal cells to 40 U of thrombin overnight Show less

Previous studies indicate that ambulance personnel have an increased risk of ill health. Shift work and time spent on physical behaviours during work and leisure are factors that could be related to health, however the research is limited. Thus, the aim of this study was to describe patterns of physical behaviours during and after work among Swedish ambulance personnel and to analyse the associations between physical behaviours and different work shifts. In this observational study, the physical behaviours of 63 ambulance personnel were measured over seven days using two accelerometers. Accelerometer data was processed using the MATLAB program Acti4, to identify physical behaviours i.e. sleep, being sedentary, light physical activity (LPA), and moderate to vigorous physical activity (MVPA), during and after work. To determine the association between shift types (independent) and patterns of physical behaviours (dependent), a Multivariate Analysis of Variance was performed on data processed according to compositional data analysis. At work, the highest proportion of both MVPA and being sedentary occurred during day shifts, compared to night and 24-h shifts (MVPA: 7% vs 4% and 5%; sedentary time: 62% vs 44% and 54% respectively). Night and 24-h shifts included 31% and 18% sleep, respectively. During the after-work periods, the highest proportions of MVPA were observed after 24-h shifts (8%). Overall, there was no statistically significant difference in physical behaviours during work and after work for various shift types. However, in a sub-analysis restricted to night and 24-h shifts, a statistically significant association between shift type and composition of physical behaviours during work was observed (η In general, ambulance personnel were physically active both during and after work. At the same time, work hours entailed a substantial amount of sedentary time. Shift type was not associated with the pattern of physical behaviours among ambulance personnel. However, during 24-h shift a lower proportion of the time was spent sleeping compared to during night shift. Studies with larger sample sizes are needed to confirm these results. The online version contains supplementary material available at 10.1186/s12889-026-27335-y. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein implicated in cardiovascular disease, but its role in heart failure (HF) remains uncertain. Observational studies indicate a link between elevated Lp(a) and HF risk, but the dose-response relationship remains unexplored. This meta-analysis aimed to quantify the association between circulating Lp(a) levels and HF incidence. A systematic search of PubMed, Embase, and Web of Science identified prospective cohort studies reporting hazard ratios (HRs) for HF incidence across different Lp(a) levels. A random-effects model was applied to pool effect estimates while accounting for heterogeneity, and restricted cubic splines assessed dose-response relationships. Five prospective cohort studies with 400 631 participants were included. During a mean follow-up duration of 11.0 years, 10 598 (2.6%) patients developed HF. A high Lp(a) level was associated with an increased HF risk (HR: 1.34, 95% CI: 1.14-1.59, p < 0.001), with moderate heterogeneity (I² = 69%). Subgroup analysis showed a stronger association in studies using an Lp(a) cutoff of ≥ 50 mg/dL (HR: 1.68) compared to those with a cutoff of < 50 mg/dL (HR: 1.16, p for subgroup difference < 0.01), which completely explained the heterogeneity. The dose-response analysis revealed a nonlinear association (p for non-linearity = 0.001). HF risk increased nearly linearly below 55 mg/dL, then slowed, and plateaued at 160 mg/dL. Elevated Lp(a) is associated with an increased HF risk in a nonlinear pattern, with risk escalation slowing at higher concentrations. Show less

To ascertain the level of psychological resilience, examine the latent profiles of individuals within infertile couples who experience recurrent implantation failure (RIF), identify the relevant influencing factors, and lay a foundation for developing customized intervention strategies. Convenience sampling was adopted in this study. Participants were selected from individuals in infertile couples with RIF who attended the Second West China Hospital of Sichuan University between November 2024 and July 2025. Data were collected via a general information questionnaire and validated scales assessing psychological resilience, social support, sleep quality, family adaptability and cohesion, anxiety, and depression. Latent profile analysis (LPA) was performed to explore the psychological resilience profiles of individuals with RIF, while univariate analysis and multivariate Logistic regression analyses were employed to identify the influencing factors associated with different profile categories. A total of 303 valid questionnaires were collected, including 194 from females and 109 from males. The overall psychological resilience score was (26.66 ± 6.319). Latent profile analysis categorized psychological resilience into three subgroups: the low tenacity-low strength subgroup (31.4%), the moderate tenacity-moderate strength subgroup (53.1%), and the high tenacity-high strength subgroup (15.5%); Multivariate Logistic regression analysis indicated that gender, family adaptability and depression severity (all Marked interindividual heterogeneity exists in the psychological resilience of individuals with RIF. Gender, family adaptability and depression severity serve as the core influencing factors. In clinical practice, stratified and targeted interventions should be delivered according to distinct psychological resilience subgroups. It yields clinical implications for an association between improved psychological resilience among individuals from couples with RIF and enhanced treatment adherence. Show less

In recent studies elevated lipoprotein(a) (Lp(a)) levels have been identified as an independent and causal risk factor for atherosclerosis and coronary heart disease. This study aims to perform a comparative early health technology assessment (HTA) of olpasiran and pelacarsen for secondary prevention of coronary heart disease (CHD) in patients with atherosclerotic cardiovascular disease, familial hypercholesterolemia, and elevated Lp(a). We developed a Markov state transition model to simulate the progression of a cohort of 597 patients with history of coronary heart disease (CHD) as myocardial infarction, coronary artery disease or peripheral artery disease, familial hypercholesterolaemia in the treatment arms of OCEAN(a)-Outcomes trial (NCT05581303) [16] and Lp(a) HORIZON trial (NCT04023552). Baseline risks of CHD, costs and utilities were obtained from published sources. Clinical trial data were used to derive reductions in lipoprotein(a). Mendelian randomization study data were used to estimate clinical benefits. Annual discounting was 3.5%. The treating strategy comprising olpasiran 150 mg every 3 months in addition to standard of care saved 3.29 QALYs, compared with standard of-care alone. With 3.5% annual discounting, there were 0.23 QALYs saved. The treating strategy comprising pelacarsen 80 mg every month in addition to standard of care saved 8.63 QALYs, compared with standard of-care alone (undiscounted). With 3.5% annual discounting, there were 0.58 QALYs saved. We found that olpasiran was highly cost-effective at the annual price of 10,424.78 BGN, compared with standard-of-care alone. Pelacarsen was highly cost-effective at the annual price of 6105.99 BGN. The threshold applied is that of gross domestic product (GDP) per capita as indicated by the National Council on prices and reimbursement of medicinal products in Bulgaria. Show less

Given that abnormal lipid metabolism is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), this study seeks to investigate the relationship between serum lipoprotein(a) [Lp(a)] levels and the progression or regression of MASLD. A total of 12,962 participants undergoing transient elastography at the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University were included in the first cross-sectional study (Study 1). The longitudinal study (Study 2) included 17,661 individuals from the same center, each with at least two health check-ups involving abdominal ultrasonography. Another cross-sectional study (Study 3) included 5,927 individuals from the UK Biobank cohort who had undergone both magnetic resonance imaging proton density fat fraction (MRI-PDFF) and Lp(a) testing. Cross-sectional analysis (Study 1) revealed that elevated Lp(a) levels were inversely correlated with the severity of both hepatic steatosis and fibrosis. Longitudinal data (Study 2) further demonstrated that baseline serum Lp(a) levels were decreased in participants with the incident of MASLD, while increased in participants with the regression of MASLD during the follow-up period. A lower baseline Lp(a) level was an independent factor for new-onset MASLD and non-regression of MASLD: the fully adjusted hazard ratios (HR) were 0.895 (95%CI 0.834-0.962, Serum Lp(a) levels are inversely associated with both the progression and regression of MASLD, indicating its potential role in reflecting disease dynamics. Show less

REM (rapid eye movement) sleep deprivation causes serious impairments in hippocampus-dependent learning and memory. This study examined whether the angiotensin II receptor blocker telmisartan, given at two different doses, could reduce cognitive deficits and affect molecular pathways related to chronic REM sleep deprivation. Thirty-two male Wistar-Albino rats (200-280 g, 3 months old) were randomly divided into four groups (n = 8): control, sleep deprivation (SD), telmisartan-treated SD groups at 1 mg/kg (SD+Tel1) and 3 mg/kg (SD+Tel3). Chronic REM sleep deprivation was induced for 21 days using the modified multiple platform (MMP) method. Telmisartan or distilled water was administered orally once daily. Cognitive performance was tested in the Morris water maze, assessing escape latency and time spent in the target quadrant. After behavioral tests, hippocampal and prefrontal cortex samples were analyzed for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), glycogen synthase kinase-3 beta (GSK-3β), monocarboxylate transporter 2 (MCT2), and lactate dehydrogenase (LDH) levels, while plasma samples were analyzed for corticosterone (CORT) levels. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitrate, and glycogen were also measured. Sleep-deprived rats showed impaired learning and memory with longer escape latency and reduced time spent of target quadrant. Telmisartan-treated SD groups demonstrated significantly improved cognitive performance, increased BDNF and CREB expression, decreased GSK-3β levels, and balanced oxidative stress markers. In conclusion, telmisartan protected against cognitive and biochemical damage caused by chronic REM sleep deprivation, likely through modulation of GSK-3β/CREB/BDNF signaling and reduction of oxidative stress. Show less

Dysregulated blood lipids are a major predictor of cardiovascular events. A recent genome-wide association study (GWAS) with five clinically relevant lipid traits in 1.65 million individuals implicated over 770 genomic regions in regulating blood lipid metabolism. To translate these associations into clinical applications, a functional understanding of their roles in lipoprotein metabolism, transport and remodeling (LPmtr) is required. Here, we report the deep molecular fine-mapping of 554 of these lipid risk loci using 168 lipoprotein-related traits and all possible ratios between them in over 273,000 participants of the UK Biobank. We identified new ratio-based markers of pathways shared by multiple LPmtr genes, such as the linoleic acid fraction of the polyunsaturated fatty acid pool to reveal potential causal genes at poorly characterized lipid risk loci, the percentage of esterified cholesterol moieties in LDL particles as a proxy for soluble LDL receptor levels, and the HDL fraction of total lipoprotein particle number as a predictor of incident myocardial infarction. We demonstrate how lipoprotein fine-mapping can generate new hypotheses for drug target development while uncovering new mechanisms relevant to hyperlipidemia. Ratio-driven clustering further implicated miR-148 in TG secretion, linking ER-stress responses at postprandial state to VLDL metabolism via mTORC1, shown through series of integrated cellular assays and mouse studies. Moreover, consistent with its regulatory influence on lipid flux we identify miR-148a a previously unrecognized determinat of Show less

This study aimed to evaluate the memory health benefits of Neurocaf™, a standardized green coffee bean extract. Neurocaf was characterized for the presence of 5-hydroxytryptamide esters, eicosanoyl-5-hydroxytryptamide (EHT), and chlorogenic acids using HPLC-PDA detector. The inhibitory kinetics of Neurocaf against acetylcholinesterase (AChE) were assessed in vitro. Cognitive efficacy was further investigated in a scopolamine-induced amnesia mouse model. In a 25-day study, male Swiss albino mice (25-30 g) were pretreated orally with Neurocaf (200 or 400 mg/kg body weight) or donepezil (3 mg/kg body weight) for 14 days followed by behavioural assessments and a 7-day co-treatment with scopolamine (0.75 mg/kg, i.p.). Neurocaf exhibited mixed competitive AChE inhibition in vitro (IC₅₀ = 298.4 µg/mL). At 400 mg/kg, it significantly enhanced spatial memory performance, demonstrated by reduced transfer latency in the elevated plus maze (p < 0.01) and decreased escape latency in the Morris water maze (p < 0.001). The extract dose-dependently suppressed brain AChE activity and elevated acetylcholine levels in scopolamine-treated mice. Furthermore, it attenuated oxidative stress, upregulated BDNF/TrkB signaling, modulated apoptotic protein expression (increased Bcl2, decreased Bax), and inhibited caspase activation, offering neuroprotection against scopolamine-induced neuronal damage. These findings highlight the potential memory functions of Neurocaf, supporting its further evaluation as a candidate functional food or dietary supplement for brain health. Show less

Generation of specific antibodies against peptides by immunization requires their covalent conjugation to protein carriers to override their inherently weak immunogenicity. The vast majority of bioconjugation approaches to achieve peptide-protein constructs rely on thiol-maleimide chemistry and capitalize on a wide array of commercial maleimide-functionalized protein carriers. Disulfide-rich peptides (DRPs) possess a rigid, constrained structure that makes them ideal for designing synthetic mimics of protein regions/domains. For bioconjugation purposes, the introduction of a single spare thiol moiety into a linear peptide antigen is straightforward, while DRPs' disulfide bonds are prone to intramolecular thiophilic attack by the reactive thiolate. This unintended reactivity competes with the desired Michael addition to the maleimide moiety, ultimately disrupting the native disulfide bridging framework. As a result, DRP's tertiary structure will be altered, affording an immunogen that is a poor mimic of the native target. Although a few studies have explored the late-stage introduction of thiol-containing cross-linkers into DRP antigens for their conjugation onto protein carriers, the stability of DRPs' disulfide pattern in the presence of an extra thiol has never been examined. In this study, we systematically evaluated the influence of different spacers in "DRP-spacer-thiol" constructs under thiol-maleimide reaction conditions. Our results highlight how both linker length and flexibility are key to maintaining DRP disulfides unaltered, providing a general approach to achieve DRP bioconjugation by thiol-maleimide chemistry. We have applied our approach to a small DRP predicted to closely mimic a surface-accessible epitope of the full LINGO-1 protein and obtained a very specific antibody response upon immunization; the resulting polyclonal IgG was able to selectively bind the full-length protein in a cellular context, with stringent selectivity across its four homologs. Show less

Colorectal cancer (CRC) remains a major global health challenge, underscoring the need for reliable biomarkers to improve prognosis and therapeutic stratification. In this study, we comprehensively investigated the expression pattern, clinical significance, molecular functions, and immunological implications of LINGO1 in CRC. Integrative analyses of TCGA and GEO datasets, together with validation in 72 clinical CRC samples, demonstrated that LINGO1 is markedly overexpressed in tumors and strongly associated with advanced clinicopathological features and poor patient outcomes. Functional experiments revealed that both knockdown of LINGO1 in SW480 and LoVo cells and overexpression of LINGO1 in HCT116 cells significantly modulate malignant phenotypes, including proliferation, migration, invasion, and angiogenic capacity. Transcriptome-wide and pathway enrichment analyses further indicated that high LINGO1 expression is linked to epithelial-mesenchymal transition, angiogenesis, Wnt/β-catenin signaling, and other oncogenic pathways. Immunogenomic profiling, supported by multiplex immunofluorescence staining, showed that elevated LINGO1 is associated with an immunosuppressive tumor microenvironment characterized by reduced CD8⁺ T-cell infiltration and diminished GZMB expression, alongside upregulation of multiple immune checkpoint molecules. Collectively, our findings identify LINGO1 as a novel oncogenic driver and immune-modulatory biomarker in colorectal cancer, with potential value for prognosis and therapeutic targeting. Show less

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and synaptic dysfunction and represents the most prevalent etiology of dementia, accounting for an estimated 60-70% of all clinically diagnosed cases worldwide. The growing focus on microglia-neuron interactions in AD research highlights their diverse, region-specific responses, which are driven by the functional and pathological heterogeneity across different brain regions. Therefore, investigating the interactions between microglia and neurons is of crucial importance. To explore the regional heterogeneity of microglia-neuron crosstalk in AD, we integrated human single-nucleus RNA sequencing data from the prefrontal cortex (PFC), hippocampus (HPC), and occipital lobe (OL) provided by the ssREAD database. Our study delineated four microglial subtypes and uncovered a pseudotime trajectory activation trajectory leading to the disease-associated microglia (DAM) phenotype. The transition along this trajectory is driven and stabilized by a key molecular switch: the coordinated downregulation of inhibitory factors (e.g., LINGO1) and upregulation of immune-effector and antigen-presentation programs, which collectively establish the pro-inflammatory DAM state. Furthermore, we observed that each brain region displayed unique microglia-neuron communication patterns in response to AD pathology. The PFC and OL engage a THY1-ITGAX/ITGB2 signaling axis; the HPC predominantly utilizes the PTPRM pathway. Notably, THY1 dysregulation strongly correlates with pathology in the PFC, HPC, and OL, suggesting that microglia-neuron crosstalk in AD possesses both heterogeneity and commonality. The main contribution of this study is the systematic characterization of region-specific microglia-neuron interactions and the identification of THY1 as a potential mediator that may be targeted therapeutically to modulate microglial function in affected brain regions. Show less

Multiple sclerosis (MS) is a debilitating neurological disorder involving concurrent immune-mediated demyelination and progressive neurodegeneration. Although disease-modifying therapies (DMTs) effectively modulate peripheral immune responses and reduce relapse rates, they are ineffective at halting disease progression and promoting central nervous system (CNS) repair. This review outlines a new therapeutic approach that targets two important microRNAs: miR-219, which stimulates oligodendrogenesis and remyelination, and miR-146a, which regulates innate immune responses and neuroinflammation. We present compelling evidence showing that the dysregulation of these microRNAs establishes a cycle of inflammatory damage and regenerative failure in chronic MS lesions. Preclinical models show that supplementing with miR-219 drives oligodendrocyte precursor cell (OPC) differentiation and myelin restoration by repressing critical inhibitors, such as PDGFRα and LINGO-1. Concurrently, miR-146a modulates neuroinflammatory cascades by regulating the NF-κB pathway, promoting the polarization of microglia toward a protective M2 phenotype, and enhancing OPC maturation. Despite its therapeutic potential, there are significant challenges to its translation, including optimizing CNS-targeted delivery systems, navigating microRNA pleiotropy, and establishing biomarker-driven treatment paradigms. We propose that a dual-targeting approach leveraging advanced nanocarriers for spatiotemporal microRNA delivery represents a transformative frontier in MS therapeutics, potentially bridging the critical gap between immunomodulation and genuine neurorestoration. Show less

Sufficient physical activity has the potential to mitigate the late effects of cancer, but objective data of activity levels in patients after pediatric bone cancer are scarce. This study aimed to objectively assess physical activity levels in this population and explore differences based on patient- and treatment-related factors. As part of a cross-sectional study of a nationwide cohort of patients treated for pediatric bone sarcoma, we assessed physical activity using an accelerometer, the ActiGraph GT9X Link. Physical intensity levels were categorized as sedentary, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) and compared between subgroups stratified by sex, age, tumor location, type of surgery for tumors around the knee, and time since local therapy. Among 79 participants, 47% were female, and median age at evaluation was 19.8 years (IQR 17.5-23.9) with a median of 5.9 years (IQR 2.9-11.7) since local therapy. Mean daily sedentary time was 643 min (SD = 104), 127 min per day (SD = 58) was spent in LPA, and 63 min per day (SD = 35) in MVPA. Seventy-eight percent of participants met the World Health Organization's recommended level of MVPA. No significant differences in intensity levels were found between the various subgroups. Pediatric bone sarcoma patients seem to regain participation in higher-intensity activities post-treatment, with physical activity levels comparable to the general population. No surgical approach is superior in terms of physical activity. Implications for Cancer Survivors Shared decision-making is important in guiding the choice of local therapy and should be informed by lifestyle and individual preferences. High sedentary time suggests scope for improvement in survivorship care. Show less

This study explores the influence of congruence and incongruence in father-mother co-parenting on adolescent depression, as well as the mediating effect of self-esteem. A total of 1389 adolescents completed questionnaires assessing their levels of depression and self-esteem, while their fathers and mothers correspondingly reported on their own co-parenting behaviors using the Parental Co-parenting Scale in this cross-sectional study. Dates were analyzed using LPA, RSA, and mediation consecutively. The results show that: (1) We identified three distinct co-parenting profiles: positive parental co-parenting, negative parental co-parenting, and mixed parental co-parenting. (2) In cases of congruent parental co-parenting, high positive parental co-parenting was associated with lower adolescent depression, whereas high negative parental co-parenting was linked to higher depression, and the difference manifests in different forms among boys and girls. Girls showed nonlinear changes in depression while boys exhibited linear trends. (3) In cases of incongruence in parental co-parenting, mothers' co-parenting exerted a stronger influence on boys' depression, while girls were not affected by mothers' and fathers' discrepancies. (4) Self-esteem mediated the relationship between parental co-parenting (in)congruence and depression across both genders. This study provides evidence for the mechanism through which parental coparenting influences adolescent depression and offers a basis for future interventions targeting adolescent depression. Show less