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Duchenne muscular dystrophy (DMD) is a serious, progressive neuromuscular condition that predominantly impacts male individuals, marked by progressive muscle weakness resulting from mutations in the dystrophin gene (DMD) encoding dystrophin. DMD is a primary muscle disorder that often presents with secondary abnormalities in lipid metabolism and decreased bone mineral density. Although disturbances in circulating lipid profiles and skeletal health have been observed in individuals with DMD, their relationship remains underexplored.This study aimed to investigate the potential association between lipid metabolic disturbances and spinal bone mineral density in patients with DMD by combining clinical lipid levels and bone density with transcriptomic pathway analysis of DMD muscle tissue. Retrospective analysis was performed on 219 genetically confirmed DMD patients and 99 age-matched healthy controls. Healthy controls with a family history of genetic disorders were excluded. Clinical data included lipid profiles (triglycerides [TGs], remnant cholesterol [RC]); bone mineral density of the lumbar spine was evaluated using Dual-energy X-ray absorptiometry (DXA); and corticosteroid use, including treatment status, dose, and duration. Patients were stratified by corticosteroid exposure. Restricted cubic splines and multivariable regression models were applied to explore potential relationships between lipid parameters and bone mineral density. Bioinformatic analyses were performed on RNA sequencing data from muscle biopsy samples from patients with DMD (GSE38417 dataset) and an independent validation cohort (GSE6011 dataset), focusing on pathways related to lipid metabolism and osteoclast differentiation. Patients with DMD had higher TG, RC, and apolipoprotein B (ApoB) levels and lower high-density lipoprotein cholesterol (HDL-C) levels than healthy controls (P < 0.05). Elevated TG and RC levels were associated with reduced spine bone mineral density, independent of corticosteroid use. The bioinformatic analyses identified key pathways, including sphingolipid metabolism and osteoclast differentiation, as well as hub genes such as FCGR2B, C1QA, which are involved in lipid regulation and bone remodeling. Lipid abnormalities, particularly elevated TG and RC levels, were significantly associated with lower bone mineral density in patients with DMD. These findings suggest that lipid abnormalities are involved in bone health impairment in DMD, warranting further studies to confirm the association. Show less

Insulin resistance (IR) contributes to atherogenic dyslipidemia and elevated ASCVD risk. Apolipoprotein A1 (ApoA1)-associated lipoproteins have diverse anti-atherogenic functions, but it is unclear whether IR drives adverse changes in their proteomic composition. We hypothesized that IR is associated with an atherogenic ApoA1 proteome and that insulin-sensitizing interventions would improve its composition. We studied 861 participants without diabetes (age 47 ± 12 years, 65.5% female). IR was directly measured using the steady-state plasma glucose (SSPG) concentration via the insulin suppression test. ApoA1-associated proteins were quantified by mass spectrometry. A subset underwent interventions for 3 months (N total 108): pioglitazone, PIO Show less

The revalorization of animal by-products, such as porcine blood, is a key strategy for sustainable aquaculture and circular economy practices. This study aimed to fill the existing knowledge gap on the effects of spray-dried porcine blood hydrolysate (PBSH), assessing its potential as a functional feed ingredient for gilthead sea bream. Two practical diets were formulated: a control diet containing 5% blood meal, and a PBSH diet including 5% PBSH previously characterized in vitro. The results indicated that the PBSH diet promoted lower hepatosomatic index, a down-regulation of key hepatic lipogenic enzymes ( Show less

Intensive farming methods have improved productivity, but public concerns have arisen regarding the welfare of production animals, particularly laying hens, and consumers demand higher animal welfare standards in all animal production systems. This study evaluated the impact of conventional cage (CC) versus cage-free (CF) housing systems on the gene expression of some peptide hormones regulating food intake along the gut-brain axis in laying hens at 80 wks. Sixty thousand Hy-Line Brown hens were reared under commercial farm conditions until week 15. At 16 wks, hens were randomly assigned into two housing systems: CC (450 cm Show less

Acute lymphoblastic leukemia (ALL) remains the most frequent pediatric malignancy, accounting for approximately 34% of all pediatric cancers, with remarkable improvements in survival (approximately 85%) due to advances in chemotherapy, radiotherapy, and supportive care. However, as survival rates have increased, new challenges have emerged-particularly the growing prevalence of obesity and metabolic syndrome among survivors. This review compiles evidence from the past decade on the relationship between leukemia treatment, obesity, and metabolic risk. The findings indicate that cranial radiotherapy, corticosteroid use, and younger age at diagnosis are key risk factors for excessive weight gain and long-term metabolic disturbances. Genetic factors such as FTO, MC4R, and LEPR polymorphisms may further influence susceptibility to obesity. Nutritional analyses highlight poor diet quality, insufficient micronutrient intake, and high-fat, energy-dense dietary patterns in survivors. Beyond endocrine dysfunction, obesity and metabolic syndrome are associated with elevated cardiovascular morbidity and reduced quality of life. Personalized medicine approaches-integrating genomics, metabolomics, and lifestyle data-hold promise for targeted prevention and intervention strategies. Early detection, continuous metabolic monitoring, and health education remain essential components in the long-term management of childhood leukemia survivors. In this review, we analyzed the dietary patterns of children and long-term leukemia survivors explaining why higher rates of obesity and comorbidities appear during or after treatments, and discussed interventions to prevent these conditions. Show less

The PRO-CTCAE provides patient-reported data on symptomatic AEs. A summary metric-the ACS-reflecting total AE burden can be calculated by averaging AE-level composite scores at a given timepoint for each participant. This study investigated the psychometric properties and interpretability of this PRO-CTCAE ACS in patients with breast, lung, or head/neck cancers. We conducted a secondary analysis of a PRO-CTCAE validation dataset comprising 940 adults undergoing chemotherapy or radiation therapy (clinicaltrials.gov: NCT02158637). We focused on empirically recommended symptom terms for three cancer sites. Analyses included Spearman's correlations, coefficient alpha, and eigenvalues from the correlation matrices, confirmatory factor analysis (CFA), and principal component analysis (PCA). Latent profile analysis (LPA) was used to assess ACS interpretability in the lung cohort. Mean composite score inter-correlations were moderate (0.30-0.35), and coefficient alphas were high (0.81-0.91). Eigenvalue ratios and CFA supported retention of a single factor/component, with suitable model fit indices. ACS correlated highly with factor scores and the first principal component from the PCA. Reduced sets of terms produced reliable scores that closely approximated the full set scores and aligned with external criteria. LPA in the lung subgroup identified four latent classes; ACS differentiated high vs. low symptom burden groups but did not distinguish the two groups expressing distinct symptom profiles. The ACS demonstrated structural validity through adequately fitting linear factor models and effectively summarized symptomatic AE burden. However, similar ACS values may mask clinically distinct symptomatic AE profiles, underscoring the value of both summary metrics and profile-based approaches. Show less

Olaparib has demonstrated therapeutic potential in treating metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene mutations, especially We performed integrative transcriptomic analyses of multiple mCRPC datasets to examine the correlation between In this study, integrative transcriptomic analyses of multiple mCRPC datasets revealed a strong positive correlation between Together, these data reveal an Show less

The purpose of this population-based study was to examine whether sedentary behavior (SB) and light physical activity intensity (LPA) are associated with pain in older adults. A further aim is to investigate the psychosomatic complaints as mediators between SB and pain. Individuals aged ≥50 from the 2018 Study on Aging, Health, and Health-seeking Behavior reported on SB and LPA using the International Physical Activity Questionnaire and pain severity using a cross-culturally validated item from the bodily pain subscale of the MOS SF-36. Multivariable logistic regression models evaluated the associations of SB and LPA with pain. Bootstrapping analyses assessed whether psychosomatic complaints mediate the association between SB and pain. Among 1201 participants (mean ± SD age = 66.1 ± 11.9 years; women = 63.3%), the prevalence of SB and pain was 21.4% and 43.0%, respectively. Compared with <8 h/d, ≥8 h/d of SB was positively associated with pain (OR = 2.42, 95% CI = 1.71-3.42). However, LPA was associated with 11% lower odds of reporting pain (OR = 0.89, 95% CI = 0.81-0.98). Self-rated health (41.2%), anxiety (23.5%), comorbidity (20.6%), functional limitations (17.6%), depression (13.2%), and sleep problems (11.8%) were associated with pain and mediated the SB-pain link. The present study observed that SB and LPA were associated with pain in older adults residing in Ghana, and psychosomatic complaints were identified as potential mechanisms in the pathway between SB and pain. Managing the pain burden in old age may require shifting the 24-hour behavior from SB to LPA and addressing the inherent psychosomatic complaints. Show less

Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). Data on long-term outcomes following invasive coronary angiography (ICA) in those with elevated Lp(a) are limited. This study examined the association of Lp(a) levels with clinical outcomes after index ICA, accounting for baseline atherosclerotic plaque burden. Data were from participants with Lp(a) measurement who underwent index ICA between 2000 and 2023. Lp(a) levels were categorized as normal (<75 nmol/L), intermediate (75- < 125 nmol/L), high (125- < 175 nmol/L), and very high (≥175 nmol/L). Angiographic characteristics (severity, burden), CAD presentation (stable, acute), and subsequent clinical outcomes [acute myocardial infarction (AMI), revascularization, in-stent restenosis (ISR), and all-cause mortality] were assessed. Among 5118 participants, 973 (19.0%) had very high Lp(a). Compared with normal Lp(a), very high Lp(a) was associated with severe obstructive CAD {adjusted odds ratio (aOR), 1.51 [95% confidence interval (CI), 1.17-1.96]}, left main disease [aOR, 1.67 (95% CI, 1.22-2.29)], and a 14.04-point higher Gensini score (95% CI, 9.57-18.52). During a median (interquartile range) follow-up of 16.87 (6.38-18.99) years, participants with very high vs. normal Lp(a) had higher risk of AMI [adjusted hazard ratio (aHR), 1.20 (95% CI, 1.05-1.37)], revascularization [aHR, 1.32 (95% CI, 1.13-1.56)], ISR [aHR, 1.28 (95% CI, 1.04-1.56)], and mortality [aHR, 1.19 (95% CI, 1.05-1.34)]. Among 798 individuals undergoing coronary artery bypass grafting surgery after index ICA, those with very high vs. other Lp(a) were more likely to require subsequent percutaneous coronary intervention [aHR, 2.20 (95% CI, 1.06-4.58)]. Elevated Lp(a) levels are associated with increased burden of coronary atherosclerosis and significant residual risk for adverse outcomes following ICA, highlighting a need for targeted risk-reduction strategies. Show less

The purpose of this study was to investigate the longitudinal association of replacing stationary time (ST) with either light (LPA) or moderate-to-vigorous (MVPA) physical activity and replacing LPA with MVPA on 2-year clinical outcomes in individuals with varying severities of knee osteoarthritis. This retrospective cohort study used isotemporal substitution models to investigate the association of replacing 10-60 min of ST with LPA or MVPA and of LPA with MVPA on Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, function, and gait speed at 2 years. Device-based stationary and physical activities were monitored using accelerometry within the Osteoarthritis Initiative cohort (n = 848). All analyses were completed separately for mild-to-moderate (Kellgren-Lawrence grade = 1-2) and severe (Kellgren-Lawrence grade = 3-4) knee osteoarthritis groups. In individuals with mild-to-moderate osteoarthritis, substituting 30-60 min of ST or LPA with MVPA improved pain and gait speed at 2 years but worsened stiffness. Replacing 60 min of ST with LPA improved Western Ontario and McMaster Universities Osteoarthritis Index function. For severe osteoarthritis, substituting 30-60 min of ST or LPA with MVPA led to worsened Western Ontario and McMaster Universities Osteoarthritis Index pain and function at 2 years, whereas substituting ST or LPA with MVPA minimally impacted stiffness. Improvements in gait speed were observed with 10-to-60-min ST or LPA substitutions with MVPA. Stationary and physical activity substitutions had varying longitudinal effects in individuals with mild-to-moderate versus severe knee osteoarthritis. Individuals with mild-to-moderate and severe knee osteoarthritis may require differing physical activity prescription to improve functional and overall health outcomes. Significance/Implications: These findings underscore the importance of severity-specific physical activity recommendations to support clinical outcomes in knee osteoarthritis management. Show less

High-density lipoprotein cholesterol (HDL-C) has long been inversely associated with atherosclerotic cardiovascular disease risk, but pharmacologic efforts to raise HDL-C have consistently failed to reduce cardiovascular events. This has shifted focus from HDL quantity to quality, emphasizing functional properties such as cholesterol efflux, antioxidative capacity, and anti-inflammatory activity. Dysfunctional HDL, often modified by oxidative and inflammatory processes mediated by myeloperoxidase, loses its ability to promote reverse cholesterol transport, support endothelial function, and suppress vascular inflammation. Advanced proteomic and lipidomic studies have revealed compositional remodeling that underlies HDL's functional heterogeneity and disease-specific signatures. Functional measures like cholesterol efflux capacity and cell-free HDL assays correlate more strongly with cardiovascular outcomes than static HDL-C levels, providing a more accurate index of vascular protection. Despite the promising therapies such as cholesterol ester transfer protein (CETP) inhibitors, niacin, and apolipoprotein A-I infusions (reconstituted high-density lipoprotein (CSL112)), none have yet demonstrated definitive event reduction. Future directions include standardizing HDL functional assays, prioritizing quality over concentration, and integrating HDL-targeted and metabolic therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transport 2 (SGLT2) inhibitors, to restore HDL's protective phenotype and redefine preventive cardiology. Show less

Although familial hypercholesterolemia (FH) is a common congenital cause of elevated low-density lipoprotein cholesterol (LDL-C), it remains underdiagnosed and undertreated worldwide due to its inherent genetic heterogeneity. This study aimed to determine the prevalence of genetic variants in a Lithuanian patient cohort with clinically diagnosed FH and evaluate their possible clinical implications. A total of 172 patients were included in the retrospective analysis. The study population comprised males and females ranging from 0 to 85 years of age, with LDL-C levels exceeding 4.9 mmol/L in adults and 3.9 mmol/L in children. The subjects were divided into four groups according to the Dutch Lipid Clinic Network (DLCN) criteria (definite, probable, possible, and unlikely). Children were analyzed separately. Next-generation sequencing (NGS) has been chosen as the most appropriate technique for genetic testing. All identified variants were categorized into three groups: (1) pathogenic, (2) likely pathogenic, and (3) variants of uncertain significance. Subjects without detected variants were classified into group (4) No mutation. Women were diagnosed with FH significantly later than men ( The increasing use of NGS in FH has enhanced diagnostic capabilities and suggests population-specific genetic patterns. However, it also increases VUS detection, for which reclassification rates are still low and require strenuous efforts. Moreover, despite the benefits of genetic testing, significant gender disparities remain and require further attention. Show less

This study aims to investigate the effect of fermented onion on Liangshan black sheep's growth performance, health, meat quality, and rumen metabolite profiles. A total of 80 four-month-old female Liangshan black sheep were randomly divided into four groups of five replicate pens (four sheep per pen). Sheep were fed a basal diet supplemented with 0 (control), 10, 20% or 30% fermented onion. Compared to that of the control group, dietary supplementation with 20% fermented onion improved final body weight, ADG and ADFI; enhanced GPT and GOT activities and increased IgA, IgG, IgM, C3, and C4 levels; increased the levels of IL-4, IL-10, TGF- Show less

The aim of this study was to determine the association of immune response and lipid metabolism genes with the development of pre-eclampsia and related acute cerebral circulatory disorders in Kazakh women. Minor allele frequencies of immune response and lipid metabolism genes were determined in 1,800 healthy participants stored in the Miras Biobank of the Scientific Centre of Obstetrics, Gynaecology, and Perinatology Joint Stock Company. The main results of the study showed that TLR4 (rs4986790), PLEKHA1 (rs2281673), PLEKHG1 (rs9478812), APOE (rs7412), FTO (rs1421085) and LPL (rs285) genes were in genetic equilibrium (p > 0.05), indicating that the sample was representative and there were no significant evolutionary pressures on the studied genes. The frequencies of minor alleles in the studied sample of Kazakhs were: TLR4 - 3.3%, PLEKHA1 - 5.9%, PLEKHG1 - 27.0%, APOE - 7.8%, FTO - 28.3% and LPL - 36.0%. The obtained data can be used for further genetic studies, as well as for the development of individualised strategies for the prevention and treatment of pre-eclampsia and related complications. The identified genetic markers may help in early detection of women at increased risk of developing these conditions, which will contribute to improving clinical outcomes and reducing maternal and perinatal mortality. Show less

G-patch domain-containing protein 2 (GPATCH2), a member of the G-patch domain-containing family, has been implicated in tumor cell growth, but the link between GPATCH2 and hepatocellular carcinoma (HCC) remains uncertain. In the current study, comprehensive bioinformatics analysis revealed that GPATCH2 was markedly upregulated in HCC and positively correlated with aggressive clinicopathological features, including histologic grade, AFP, albumin level, and adjacent hepatic tissue inflammation, as well as miserable outcomes in HCC. GPATCH2 also has certain diagnostic value for HCC, histologic grade, and 1-, 3-, and 5-year survival outcomes. Functionally, loss-of-function experiments disclosed that silencing GPATCH2 suppressed HCC cell proliferation, migration, invasion, and xenograft tumor growth in the subcutaneous mouse model. Silencing GPATCH2 also resulted in an increase in the expression level of CDH1, while causing a decrease in the expression levels of FN1, TWIST1, SNAI1, and SNAI2. Rescue experiments further confirmed SNAI2 as a critical downstream effector mediating GPATCH2-driven oncogenic activity in HCC. Mechanistically, GPATCH2 was uncovered to be transcriptionally activated by the transcription factor Yin Yang 1 (YY1), and can mediate the role of YY1 in promoting HCC progression and elevating SNAI2 expression. Taken together, GPATCH2 is a YY1-regulated oncogenic driver that promotes HCC advancement through SNAI2, highlighting its potential as a diagnostic, prognostic, and therapeutic target for HCC. Show less

Accurate diagnosis of B-cell chronic lymphoproliferative disorders (B-CLPDs) remains challenging due to overlapping phenotypes across subtypes. Machine learning (ML) offers promising tools to improve marker evaluation and refine flow cytometry analysis. We investigated the use of ML algorithms to evaluate the diagnostic value of incorporating CD148, CD180, and CD200 into standard B-CLPD phenotyping panel and to develop a diagnosis decision tree. We trained models with flow cytometry data from 480 patients with B-CLPDs using XGBoost and DecisionTree algorithms. The final models integrated 2 categorical markers (CD5 and CD10) and quantiles of fluorescence intensity of 4 quantitative markers (CD20, CD180, and CD200) to classify 6 B-CLPD subtypes. These trained models were applied to an independent cohort of 433 patients with B-CLPD analyzed on a different flow cytometer platform. DecisionTree models achieved the highest classification accuracy (mean accuracy, 0.88) in the validation cohort. The overall specificity ranged from 0.95 lymphoplasmacytic lymphoma (LPL) to 1 hairy cell leukemia (HCL), whereas sensitivity varied from 0.75 (LPL) to 1 (HCL). The DecisionTree model demonstrated superior identification of chronic lymphocytic leukemia compared to a Matutes score of 4 or 5 (P = .029). In more than half of the cases, a diagnosis was determined with near certainty using only the cytometry data. For the remaining cases, a hierarchical approach incorporating additional tests was proposed. For practical implementation, an interactive interface provides diagnostic predictions, positive predictive values, and Gini index scores. This study establishes a ML-optimized strategy for B-CLPD classification, combining phenotypic, cytogenetic, and molecular data to enhance diagnostic accuracy of leukemic B-CLPD cells. This trial was registered at www.ClinicalTrials.gov as #NCT04952974. Show less

Lipokines are a class of lipid-derived signaling molecules, playing essential roles in regulating metabolic homeostasis and systemic metabolism. In this review, we first comprehensively describe six major lipokines, including palmitoleic acid (C16:1n7), 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), fatty acid esters of hydroxy fatty acids (FAHFAs), 12-hydroxyeicosapentaenoic acid (12-HEPE), lysophosphatidic acid (LPA), and 15-hydroxyeicosatetraenoic acid (15-HETE), focusing on their mechanistic roles in energy metabolism and inflammatory modulation as well as their cross-talk within different signaling pathways. These lipokines collectively contribute to metabolic homeostasis by regulating multiple pathways, including insulin signaling, AMPK activation, inflammatory modulation, and G-protein-coupled receptor-mediated pathways. Furthermore, we clarify the associations between lipokines and various diseases such as obesity, type 2 diabetes, cardiovascular diseases, non-alcoholic fatty liver disease, inflammatory disorders, and cancer, and discuss their potential as biomarkers and therapeutic targets. Despite current challenges, including functional complexity, limitations of model systems, and difficulties in clinical translation, lipokines demonstrate promising prospects in the prevention and treatment of metabolic diseases and application in precision medicine. Future research should prioritize the elucidation of the specific action mechanisms of different lipokines, development of highly sensitive detection methodologies, and large-scale clinical trials to facilitate the translation of the research results into practical medical applications. Show less

Previous research has reported the efficacy of porcine brain hydrolysate (PBH) in improving Alzheimer's disease (AD). Nevertheless, the identification and screening of peptides with memory-enhancing effects within PBH remains ambiguous. The memory-enhancing effect of PBH was evaluated through animal and human experiments. Peptides with potential memory-enhancement effects were screened using molecular docking based on key target proteins (Keap1, BACE1, AChE, and p38α), and confirmed through cellular experiments. Results showed a significant reduction in behavioral errors of mice and marked improvements in the memory scores of humans. Five peptides with potential memory-enhancing effects were identified and screened. Cell experiments demonstrated that the cell activities were increased to 89.83 % and 78.14 % respectively for FPLHP and WGQKPW. Furthermore, the two peptides could reduce the contents of the four target proteins, thereby exhibiting the potential of memory enhancement. These findings offer a novel strategy for the discovery of peptides, which contribute to the development of memory-enhancing. Show less

Pancreatic cancer (PC) represents a highly lethal malignancy characterized by diagnostic challenges owing to nonspecific early symptoms and insufficiently sensitive biomarkers. This investigation sought to identify novel PC biomarkers through lipidomic profiling, an emerging metabolomics methodology examining lipid pathways in disease pathogenesis. We established a humanized murine PC model. Small-molecule oxidized lipid metabolites in primary pancreatic tumors and hepatic metastases were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) integrated with a comprehensive metabolomics platform. Multivariate statistical approaches including principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were systematically applied. Analysis identified 64 differentially expressed oxidized lipids structurally classified as unsaturated fatty acid derivatives. Comparative assessment of metabolic profiles revealed a pronounced reduction in prostaglandins (PGE Our findings establish prostaglandins PGE Show less

Embryonic stem cells can be instructed to form gastruloids, an efficient four-dimensional model for studying some aspects of post-implantation embryonic patterning, which undergo gastrulation-like processes, illustrating their robust self-organizing capacity to form embryo-like patterns. Here, we study the molecular and cellular mechanisms underlying this remarkable property and report that self-organization competence is associated with a cell-specific coordination of a cadherin switch. E-cadherin repression by Snai1 is indeed critical for this process, with Snai1 triggering the cell-specific pace of pluripotency exit, thus allowing a coordinated transition from E- to N-cadherin to occur. In contrast, we find that N-cadherin inactivation unleashes gastruloids' morphogenetic competence, for it leads to the formation of embryo-like structures with proper rostro-caudal somite patterning without requiring any addition of extracellular matrix. Altogether, this work establishes a molecular mechanism that integrates the exit from pluripotency and the pace of cell differentiation, leading to the self-organizing potential of gastruloids. Show less

Currently, understanding of the nonlinear relationship between age and hepatocellular carcinoma (HCC) prognosis is insufficient. Thus, this study aimed to analyze the relationship between age at HCC diagnosis and overall survival (OS) and identify possible influencing mechanisms. Clinical data from the TCGA public database were analyzed. Restricted cubic spline and segmented logistic regression were employed to explore the nonlinear relationship between age at diagnosis and mortality risk following hepatectomy. Furthermore, bioinformatics methods were employed to understand the possible mechanisms of this nonlinear relationship at the genetic level. The results indicated a nonlinear relationship between age at diagnosis and OS, with the age of 60 years identified as a critical point. Segmented regression showed that age ≥60 years is an unfavorable prognostic factor. The "DNA mismatch repair" pathway was considerably enriched in patients aged <60 years. However, the gene mutation rate of "APOB," "MUC16," "ALB," and "PCLO" and the median tumor mutation burden were relatively more evident in patients aged ≥60 years. MGEA12 was more highly expressed in tumor tissues than in normal ones, particularly in patients aged ≥60 years. The survival rate of the high-expression group was lower than that of the low-expression group. At the mRNA level, the MGEA12 expression in Huh-7 and SUN449 was higher than that in the HSC-LX2 cell line. A nonlinear relationship was found between age at HCC diagnosis and OS, with the age of 60 years being the critical point. MGEA12 may affect the prognosis of elderly people. Show less

Sudden cardiac death (SCD) is a known risk of hypertrophic cardiomyopathy (HCM), especially in asymptomatic and younger (<35 years old) populations. There are several mutations that cause HCM, most notably within the MYBPC3 and MYH7 genes. ALPK3 (alpha protein kinase 3) has been identified as a gene of interest in HCM, specifically associated with late-onset adult HCM or pediatric cases which typically present with musculoskeletal and facial deformities. In this report, we present a case of SCD due to HCM in a young, reportedly asymptomatic patient without dysmorphia that had a specific mutation of the ALPK3 gene and a striking gross pathological appearance previously undiscussed in literature. Show less

Physical activity (PA), sedentary behaviour (SB) and sleep (SLP)-key components of 24-h movement behaviours-have each been independently linked to motor development in preschool children. However, the lack of understanding regarding their integrated and mutually exclusive nature has limited research on their combined impact on early health outcomes. This study employed compositional data analysis (CoDA) to examine the relationships between these behaviours and fundamental movement skills (FMS), as well as potential changes in FMS resulting from isotemporal reallocation. A cross-sectional study was conducted with 292 preschool children (3-6 years old; 149 boys and 143 girls). SB, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were measured using accelerometers, whereas sleep duration was parent-reported. FMS, including locomotor skills, object-control skills and total motor skills (total MS), were assessed using the third edition of the Test of Gross Motor Development (TGMD-3). CoDA was used to analyse the relationship between 24-h movement behaviours and FMS. After adjusting for gender, age, family socioeconomic status (SES) and the number of children in the household, a higher proportion of MVPA was significantly positively associated with both total MS (β = 9.39, p = 0.008) and locomotor skills (β = 6.69, p = 0.003). In a 15-min isotemporal reallocation model, substituting MVPA for other behaviours resulted in significant improvements in both total MS and locomotor skills. Dose-response analysis revealed that reallocating even a small amount of time (e.g., 15 min) to MVPA resulted in meaningful benefits for FMS. Notably, this relationship was asymmetric: The negative impact of reducing MVPA outweighed the gains from increasing MVPA. These findings highlight the importance of prioritizing MVPA within the 24-h movement behaviours framework to optimize motor development in preschool-aged children. Show less

Growth differentiation factor 15 (GDF15) is a key regulator of food intake and energy metabolism. GDF15 mimetic drugs for the treatment of metabolic syndrome and obesity are under clinical development. While GDF15 presents a promising target for weight management, its potential cardiovascular actions remain elusive. In this study we investigated the role of GDF15 in macrophage function and atherosclerosis pathogenesis and whether GDF15 acts both as a biomarker and mediator of atherosclerosis severity. ApoE Show less

Although several retrospective studies have investigated the association of TP53 rs1042522 and ApoB rs693 with the risk of biliary tract cancer (BTC), results have been inconsistent. In this study, to provide evidence from a prospective study, we analyzed the association of these two genetic polymorphisms with BTC risk using data from the Japan Public Health Center-based Prospective Study. We conducted a case-cohort study with 152 BTC cases and 12,159 subcohort subjects and estimated HRs and 95% confidence intervals (CI) using a weighted Cox proportional hazards model. TP53 rs1042522 showed a statistically significant association with the risk of BTC (HR, 1.89; 95% CI, 1.27-2.82, in the recessive genetic model), whereas ApoB rs693 showed no apparent association. Of interest, TP53 rs1042522 seemed to be associated with BTC risk in a recessive model, but not in a dominant model. On comparison of three BTC subtypes, TP53 rs1042522 seemed to be associated with the incidence of gallbladder cancer and extrahepatic bile duct cancer (HR, 2.21; 95% CI, 1.14-4.28 and HR, 1.97; 95% CI, 1.00-3.88, respectively) but showed only a nonsignificant association with intrahepatic bile duct cancer (HR, 1.58; 95% CI, 0.63-3.96). In this prospective case-cohort study, we found evidence to support an association between the TP53 rs1042522 polymorphism and the risk of BTC. The null finding for ApoB rs693 might be due to the extremely low T-allele frequency (4.4%) in the study population. This prospective study highlights the effect of TP53 rs1042522 on BTC risk in Japanese individuals. Identifying carriers of the high-risk CC genotype may facilitate targeted surveillance and early detection strategies, potentially reducing mortality and improving outcomes. Further large-scale studies are required to clarify environmental interactions and optimize prevention. Show less