📋 Browse Articles

Computerized cognitive training allows real-time tracking of performance metrics that may serve as digital biomarkers. This study investigated the value of a novel in-game digital biomarker, RTACC (Reaction Time-Accuracy Correlation), the correlation between reaction time and accuracy, using data from 130 participants with mild cognitive impairment enrolled in the intervention arm of the SUPERBRAIN-MEET randomized controlled trial. Participants underwent a 24-week multi-domain intervention, consisting of computerized cognitive training, physical exercise, nutritional education, vascular/metabolic risk management, and motivation enhancement. RTACC was derived from task-level RT and accuracy and examined in relation to cognitive and biomarker outcomes. Linear regression analysis revealed a significant association between RTACC and changes in Repeatable Battery for the Assessment of Neuropsychological Status scores from baseline to 24 weeks (beta coefficient = -11.90 ± 3.78, T = - 3.14, P = 0.002). RTACC also showed a marginal effect on changes in brain-derived neurotrophic factor levels (beta coefficient = - 3.13 ± 1.64, P = 0.057). Logistic regression analysis demonstrated that RTACC combined with clinical information identified good responders with an area under the receiver operating characteristic curve of 0.73 (95% CI: 0.62-0.84). These findings suggest that this in-game digital biomarker (RTACC) may help identify individuals likely to benefit from multi-domain intervention. Show less

Tuberculous pyomyositis is a rare and often under-recognized extrapulmonary manifestation of tuberculosis, presenting with non-specific symptoms such as fever and abscess, that may delay diagnosis. We report a unique case of disseminated tuberculous pyomyositis in a 56-year-old male with underlying chronic inflammatory arthritis. The diagnosis was confirmed using CBNAAT, line probe assay (LPA), and histopathology. Currently MRI is the standard imaging modality in use for imaging pyomyositis. Show less

Endometriosis (EDT) is a chronic, estrogen-dependent disease characterized by inflammation, fibrosis, pelvic pain, and infertility. Current therapies show limited long-term efficacy and adverse effects, underscoring the need for novel therapeutic approaches. Elevated copper (Cu) levels have been reported in both patients and animal models of EDT, making Cu chelation a promising strategy. This work aimed to evaluate the impact of ammonium tetrathiomolybdate (TM) on the expression of markers related to the interconnected processes of inflammation, innervation, and fibrogenesis in mice with induced EDT. Twenty-four female C57BL/6 mice were assigned to Sham, EDT, or EDT+TM groups. Treatment with TM began on postoperative day 15, with samples collected one month after EDT induction. Peritoneal fluid cytokines (TNF-α, IL-1β, IL-6, TGF-β1) were quantified by ELISA. Endometriotic-like lesions were examined for mRNA expression of cytokines, neurotrophins ( Show less

The glucagon-like peptide-1 receptor (GLP-1R) has emerged as a promising therapeutic option for alcohol use disorder (AUD), yet the underlying mechanisms and neurocircuitry involved remain unclear. This study aimed to analyze GLP-1R gene expression changes in brain regions associated with alcohol's effects, including the prefrontal cortex (PFC), nucleus accumbens (NAc), and hippocampus (HIP), in mice following 42 days of voluntary ethanol consumption (VEC; 10% v/v) and postmortem samples from 18 patients with AUD. Additionally, we examined the expression of OPRM1 (mu-opioid receptor) and BDNF (brain-derived neurotrophic factor), key targets related to alcohol intake and reward, in the NAc and HIP, respectively. GLP-1R gene expression was significantly reduced in all brain regions of ethanol-exposed mice and AUD patients. These reductions paralleled decreased OPRM1 and BDNF expression in the NAc and HIP, respectively. Pearson and Spearman correlation analyses revealed no significant associations between gene expression and age, RIN, pH, postmortem interval (PMI), body mass index (BMI), smoking status, age of onset of alcohol use, or years of drinking. In summary, chronic alcohol consumption in humans or mice was associated with decreased GLP-1R gene expression in brain regions involved in the reinforcing effects of ethanol. These findings open new avenues for further research into how this emerging receptor could serve as a potential biomarker and therapeutic target in AUD. Show less

Recreational sedentary screen time (rSST) is the most prevalent form of discretionary sedentary behavior and is strongly linked to poor health outcomes. However, the relationship between time spent in rSST and other 24-h behaviors is not well understood. The purpose of this study was to examine between- and within-day associations between rSST and other 24-h behaviors that include other non-rSST sedentary time (other-SED), standing (STAND), light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), and total sleep (SLEEP). Baseline data from participants randomized to the StandUPTV study, an intervention aimed to reduce rSST in adults, were included. All 24-h behaviors were assessed continuously for 7-days. The activPAL device was used to assess rSST, other-SED, STAND, LPA, and MPVA; SLEEP was assessed using a GENEactiv accelerometer. rSST was collected using Wi-Fi plugs to capture TV time and tablet app usage. A multilevel modelling approach was used to assess bidirectional associations between rSST (total, daytime, evening) and 24-h behaviors at the between-person (across persons) and within-person (across days) levels, adjusting for age, sex, chronotype, education level, and week versus weekend day. The results were scaled hourly for interpretation. On average, 8.0 ± 1.6 days of continuous daily 24-h behavior data were included from 94 participants (age [M ± SD: 42.3 ± 11.5] years; 82% female; 78% White; BMI [M ± SD: 29.8 ± 7.8] kg/m This is the first known analysis of the bidirectional relationship between rSST and 24-h behaviors. The negative association between rSST and other-SED suggests that rSST may displace rather than contribute to more cumulative sedentary time. These findings advocate that contexts of sedentary behavior should be considered as distinct behavioral targets in intervention development. Future interventions targeting rSST reduction should also include strategies to reduce total sedentary time. NCT04464993. Show less

Obesity-related health issues, including cognitive decline linked to hippocampal neurogenesis and neuroplasticity, are gaining more attention as obesity rates rise worldwide. Physical activity is recognized as a potent stimulator of neurotrophic factors. This study examined the impact of six weeks of treadmill training on hippocampal molecular pathways in adult female Zucker diabetic fatty (obese) and Zucker lean rats. Animals were assigned to either treadmill exercise (n = 10) or sedentary control (n = 10) groups. Endurance training (ET) markedly upregulated mRNA expression of brain-derived neurotrophic factor and its receptor. The PI3K/Akt pathway was upregulated only in the trained lean rats and downregulated in the trained obese group compared with sedentary controls. ET elicited divergent effects on neurotrophin-associated PLCγ/PKC/CAMKII signalling between lean and obese groups. Sedentary obese rats primarily utilized the PLCγ/PKC axis, while both trained groups (lean and obese) showed increased CAMKII expression, associated with enhanced synaptic plasticity and memory. Enhanced synaptophysin mRNA indicated improved synaptogenesis and plasticity following ET. Trained obese rats also exhibited reduced expression of the microglial pro-inflammatory marker Iba1, alongside increased markers of oligodendrocyte regeneration and neurofilament expression. Behavioral assessment via the passive avoidance test demonstrated improved learning and memory in trained obese animals. Collectively, these findings suggest that ET may mitigate obesity-induced hippocampal damage, exert neuroprotection, and enhance hippocampal function. Show less

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., Show less

Olive pomace (OP), a by-product of olive oil production, is a sustainable resource rich in bioactive compounds with potential applications in cosmetics and pharmaceuticals. This study investigates the protective effects of olive pomace juice (OPJ) against H Show less

Current evidence is unclear due to methodological limitations. We bridge critical knowledge gaps by quantifying the longitudinal changes in movement behaviours and their correlates from early childhood through adolescence. Longitudinal observational cohort study. General healthy child and adolescent sample in Singapore. Growing Up in Singapore Towards healthy Outcomes study participants. We used wrist-worn accelerometry and proxy-reported data to examine movement behaviours (sleep, inactivity, light physical activity (PA; LPA) and moderate-to-vigorous PA (MVPA) and screen-viewing) at ages 5.5, 8, 10 and 12 years and the sociodemographic and maternal lifestyle-related correlates using linear regression models with generalised estimating equations. Among 837 children, sleep, LPA and MVPA declined by 3% (from 9.1 to 8.8 hours/day), 24% (from 5.8 to 4.4 hours/day) and 44% (from 71.3 to 40.1 min/day), respectively, while inactivity and screen viewing increased by 26% (from 8.0 to 10.1 hours/day) and 155% (from 1.8 to 4.6 hours/day), respectively, from ages 5.5 to 12 years. The greatest annual increase in inactivity (0.6 hour/annum) and screen-viewing (0.8 hour/annum) and decrease in LPA (0.3 hour/annum) and MVPA (10.4 min/annum) occurred from ages 8 to 10 years. Girls of Malay ethnicity and lower socioeconomic status, and whose mothers had less favourable movement behaviours, had significantly less sleep, higher inactivity and screen-viewing and/or lower PA. Maternal PA levels and/or sitting time were associated with children's sleep, inactivity and MVPA up to age 8 years, while maternal sitting and screen-viewing behaviours were associated with children's screen-viewing at all ages. Using contemporaneous datasets relevant to the present day, we confirmed that children become less physically active and have longer screen-viewing as they transition into adolescence and highlighted characteristics to be prioritised in future interventions. Show less

Massive open online courses (MOOCs) have transformed global education, yet their long-term effectiveness and evolving learner engagement remain underexplored. This study aims to comprehensively evaluate a nursing MOOC over six years, examining learner engagement, identifying distinct learner profiles, and assessing changes across different developmental stages to inform future MOOC design. A retrospective study was conducted on 4171 completers of the Medical Nursing MOOC on a Chinese MOOC platform, covering eleven semesters from 2018 to 2023. Latent profile analysis (LPA) categorized learners based on unit test scores, and profile distributions were compared across the MOOC's developmental stages. The Medical Nursing MOOC attracted 69,642 registrants with a 5.99% completion rate. Among the 4171 individuals who completed the course, latent profile analysis identified six distinct learner types, demonstrating significant differences in overall learning effect (H = 2823.604, P < 0.001). The chi-squared analysis revealed significant differences between the proportions of the six profiles regarding MOOC developmental stages (χ Findings highlight the evolving role of MOOCs in nursing education. Despite challenges in long-term engagement, the increasing proportion of highly engaged learners and declining dropout rates indicate growing effectiveness and sustainability. These insights provide evidence-based guidance for optimizing MOOC design and implementation. Show less

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are debilitating disorders with overlapping symptoms such as chronic pain and fatigue. Dysregulation of the endogenous opioid system, particularly µ-opioid receptor function, may contribute to their pathophysiology. This study examined whether epigenetic modifications, specifically µ-opioid receptor 1 gene ( Show less

Novel therapeutic approaches, such as exosome therapy, have garnered considerable attention for the treatment of central nervous system (CNS)-related disorders. This study aimed to investigate the effect of Neural stem cell-derived exosomes(Exo-NSC) on improving behavioral, molecular, and electrophysiological symptoms. Rats were divided into: control, lesioned groups (Alz, Alz + saline), treatments (Alz + NSC, Alz + Exo-NSC). the nucleus basalis of meynert (NBM) was lesioned using electrical lesion. One week after lesion, saline, NSC, and Exo-NSC were injected into the NBM. Twenty-eight days post-injection, behavioral tests (passive avoidance memory and locomotor activity) and EEG recordings were conducted. Subsequently, hippocampal levels of brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) were measured. NBM lesioning significantly reduced the step-through latency (STL), decreased alpha and gamma wave frequencies, increased theta and delta wave frequencies, and reduced Ach and BDNF levels compared to the control group. The NSC injection resulted in decreased delta wave frequency, increased gamma wave frequency, and elevated BDNF levels. Meanwhile, Exo-NSC injection significantly increased STL, beta and gamma wave frequencies, and levels of ACh and BDNF compared to lesioned groups. Overall, the findings indicate that Exo-NSC injection may be more effective than NSCs in improving passive avoidance memory. This benefit may stem from elevated hippocampal ACh and BDNF levels in the hippocampus. Show less

Data are limited regarding national clinician awareness, testing, and treatment of lipoprotein(a) [Lp(a)]. We conducted a national survey of US clinicians to investigate these issues. An internet-based survey of awareness, testing and treatment of Lp(a) was administered by a medical survey company to clinicians who have been in practice ≥5 years in the US or its territories. 2002 clinicians completed the survey: 47 % were primary care, 35 % cardiology, 9 % endocrinology, and 9 % neurology. 28 % were female, 24 % Asian, 4 % Hispanic, and 3 % Black. Most clinicians agree knowing the Lp(a) level can improve risk assessment and patient engagement. Patients with premature or recurrent CVD events are most likely to be targeted for Lp(a) testing and for prescribing possible future Lp(a)-targeted therapies. Show less

Although increased maternal androgens, such as those in polycystic ovary syndrome (PCOS), are associated with a higher incidence of autism spectrum disorder (ASD) in offspring, a causal link has yet to be established. We assessed whether perinatal hyperandrogenization in a murine model recapitulates core ASD traits and compared this model to the maternal immune activation (MIA) model of ASD. Both models produced ASD-like phenotypes, yet they exhibited distinct behavioral subtypes and neurodevelopmental trajectories. Hyperandrogenized offspring showed greater reductions in social communication (neonatal USVs, d = 0.633-0.773; juvenile USVs, d = 1.103-1.216; social preference, d = 0.715), whereas only MIA offspring showed increased repetitive behaviors (d = 0.599). Ex vivo magnetic resonance imaging revealed volume increases in specific cortical regions in both models, with MIA additionally showing absolute cingulate cortex enlargement, and hyperandrogenized mice displaying focal increases in sexually dimorphic regions, despite a 36% reduction in overall brain volume (FDR 10%). Placentas from both groups showed reduced LIX (CXCL5), but distinct immune shifts also emerged: MIA placentas exhibited elevated IL-4 and IL-1β, whereas hyperandrogenized placentas showed increased TNFα. In neonatal brains, both conditions were associated with reduced IL-2, with MIA additionally decreasing IL-17A and IL-12p70, suggesting suppression of Th1/Th17-type cytokine signaling that normally supports proinflammatory and immune-neural interactions. DRD2 and BDNF protein were upregulated in hyperandrogenized fetal brains but downregulated with MIA. These results suggest that hyperandrogenization and MIA act through distinct mechanisms, producing subtle neurodevelopmental and behavioral differences consistent with human ASD subtypes. Show less

Previous studies have shown that plasma amyloid-beta oligomers (AβOs), the toxic form of amyloid-beta (Aβ), are a critical issue in the development or worsening of Alzheimer's disease (AD) and can be regarded as a blood marker for screening in dementia. We examined plasma AβOs with their related biomarkers in a case-control study to clarify these issues. A total of 16 patients diagnosed with Alzheimer's dementia (AD) and 16 cognitively normal controls (NCs) were recruited to compare their plasma biomarkers, AβO, Aβ Show less

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by decreased amyloid-beta (Aβ) clearance, enhanced Aβ aggregation, an increased risk of amyloid-related imaging abnormalities (ARIA), and blood-brain barrier (BBB) dysfunction. The Show less

Training adaptation involves muscular-metabolic remodeling and personality-linked traits such as motivation, self-regulation, and resilience. This narrative review examines how training load oscillation (TLO)-the deliberate variation in exercise intensity, volume, and substrate availability-may function as a systemic epigenetic stimulus capable of shaping both physiological and psychological adaptation. Fluctuating energetic states reconfigure key energy-sensing pathways (AMPK, mTOR, CaMKII, and SIRT1), thereby potentially influencing DNA methylation, histone acetylation, and microRNA programs linked to PGC-1α and BDNF. This review synthesizes converging evidence suggesting links between these molecular responses and behavioral consistency, cognitive control, and stress tolerance. Building on this literature, a systems model of molecular-behavioral coupling is proposed, in which TLO is hypothesized to entrain phase-shifted AMPK/SIRT1 and mTOR windows, alongside CaMKII intensity pulses and a delayed BDNF crest. The model generates testable predictions-such as amplitude-dependent PGC-1α demethylation, BDNF promoter acetylation, and NR3C1 recalibration under recovery-weighted cycles-and highlights practical implications for timing nutritional, cognitive, and recovery inputs to molecular windows. Understanding TLO as an entrainment signal may help integrate physiology and psychology within a coherent, durable performance strategy. This framework is conceptual in scope and intended to generate testable hypotheses rather than assert definitive mechanisms, providing a structured basis for future empirical investigations integrating molecular, physiological, and behavioral outcomes. Show less

Brain-derived growth factor, BDNF, has critical roles in a wide variety of neuronal aspects, including cell survival, differentiation, and synaptic function after their maturation. TrkB, a high-affinity receptor for BDNF, is a major contributor in these neuronal aspects, and its functions are exerted via stimulating intracellular signaling pathways including the mitogen-activated protein kinase (MAPK) pathways. As a family of MAPKs, the functions of ERK1/2, p38MAPK, and JNKs have been extensively studied using in vivo and in vitro neuronal systems. ERK 1/2, a major serine-threonine kinase and belonging to the MAPK family, also works as a downstream molecule after activation of the BDNF/TrkB system. Interestingly, growing evidence has demonstrated that ERK1/2 signaling exerts a positive or negative influence on neurons in both healthy and pathological conditions in the central nervous system (CNS). Indeed, activation of ERK 1/2 stimulated by the BDNF/TrkB system is involved in the regulation of synaptic plasticity. On the other hand, overactivation of ERK1/2 signaling under pathological conditions is closely related to neurodegeneration. Furthermore, cell stress activates p38MAPKs and JNK signaling, contributing to the progression of neurodegeneration. In this review, we show how MAPK pathway signaling affects neuronal fate, including cell survival or cell death, in the CNS. Moreover, we discuss the involvement of overactivation of MAPK signaling in the neurodegeneration observed in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Show less

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants-astaxanthin and Show less

Ischemic stroke is one of the leading global causes of disability and death. Despite advances in modern medical technology that improve acute treatment and rehabilitation measures, post-stroke anxiety and depression (PSD) do not receive sufficient attention. To systematically evaluate risk factors and early identification markers for PSD for more precise screening and intervention strategies in clinical practice. This retrospective study analyzed clinical data from 112 patients with ischemic stroke admitted between January 2022 and December 2024. Based on assessments using the Hamilton Rating Scale for Anxiety (HAMA) and Hamilton Rating Scale for Depression (HAMD) at 2 weeks (± 3 days) post-stroke, patients were classified into the PSD group (HAMA ≥ 7 and/or HAMD ≥ 7) and the non-PSD group (HAMA < 7 and HAMD < 7). Observation indicators included psychological assessment, demographic and clinical characteristics, stroke-related clinical indicators, neuroimaging assessments, and laboratory biomarkers. Multivariate logistic regression analysis was used to identify independent risk factors for PSD, and receiver operating characteristic curve analysis was used to evaluate the diagnostic value of potential biomarkers. Of the 112 patients, 46 (41.1%) were diagnosed with PSD. Multivariate analysis identified five independent risk factors: Female gender [Odds ratio (OR) = 2.32, 95% confidence interval (CI): 1.56-3.45], history of mental disorders prior to stroke (OR = 3.17, 95%CI: 1.89-5.32), infarct location in the frontal lobe or limbic system (OR = 2.86, 95%CI: 1.73-4.71), stroke severity with National Institutes of Health Stroke Scale ≥ 8 at admission (OR = 2.54, 95%CI: 1.62-3.99), and low social support (Social Support Rating Scale < 35, OR = 2.18, 95%CI: 1.42-3.36). Subgroup analysis showed that depression patients more commonly had left hemisphere lesions (68.4% PSD is a complex neuropsychiatric consequence of stroke involving disruption of the frontal-limbic circuitry, neuroinflammatory responses, and dysfunction of the hypothalamic-pituitary-adrenal axis. Show less

Benign prostatic hyperplasia (BPH) is a common public health problem in ageing men worldwide. Diarylpropionitrile, a selective ERβ agonist, favorably regulates cell proliferation and inflammation, two major hallmarks of BPH pathology. This study aimed to explore the mitigative impact of diarylpropionitrile on testosterone-driven BPH in rats. 40 Sprague Dawley male rats aged 2.5-3 months were randomly divided into 4 groups (n = 10): a normal control group, a testosterone-induced BPH group, a finasteride-treated group, and a diarylpropionitrile-treated group. BPH was induced by daily subcutaneous testosterone injections for 4 weeks, with finasteride and diarylpropionitrile administered orally once daily for the same duration, one hour before each testosterone injection. After 4 weeks of treatment, macroscopic and microscopic features of prostatic hyperplasia and androgenic, proliferative, angiogenic, apoptotic, and inflammatory biomarkers in prostatic tissue homogenates were assessed. Testosterone administration significantly increased prostate weight, prostatic index, and hyperplasia scores, while treatment with either diarylpropionitrile or finasteride effectively ameliorated these testosterone-induced changes. Both treatments significantly lowered elevated prostatic DHT, 5αR2, β-catenin, and PCNA levels, demonstrating a strong anti-proliferative effect. They also attenuated the increased pro-inflammatory cytokines IL-6, IL-27, and PGE2 and growth factors TGF-β and VEGF. Furthermore, both agents inhibited testosterone-induced ERβ upregulation and increased expression of the anti-apoptotic protein BCL2. There were no substantial differences comparing finasteride and diarylpropionitrile in the majority of the tested parameters. Diarylpropionitrile alleviates testosterone-driven BPH in rats by modulating key pathways associated with cellular proliferation and inflammation. Diarylpropionitrile, as an ERβ agonist, represents a promising alternative for the BPH treatment through multi-targeted mechanisms. Show less

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Among the genetic risk factors linked to AD, the Apolipoprotein E4 (ApoE4) remains the strongest. It is well known that carrying the ApoE4 isoform is associated with advanced AD pathology, blood-brain barrier (BBB) disruption, and changes in lipid metabolism. In this review, we provide an overview of the role of centrally and peripherally produced ApoE in AD. After this introduction, we focus on new findings regarding ApoE4's effects on AD pathology and BBB function. We then discuss ApoE's role in lipid metabolism in AD, highlighting examples of lipid changes caused by carrying the ApoE4 isoform. Next, the review explores the implications of ApoE4 isoforms for current treatments-whether they involve anti-amyloid therapy or other pharmacological agents used for AD-emphasizing the importance of personalized medicine approaches for patients with this high-risk allele. This review aims to provide an updated overview of ApoE4's effects on AD pathology and treatment. By integrating recent discoveries, it underscores the critical need to consider ApoE4 status in both research and clinical settings to enhance therapeutic strategies and outcomes for individuals with AD. Show less

Depressive disorders often show recurrent courses that cannot be sufficiently prevented by existing therapeutic protocols. In other affective disorders, recurrence has been linked to three mechanisms -spontaneous recovery, accelerated new/relearning, and reinstatement- which are related to the preservation of disorder-related memory traces even through successful extinction-based interventions. Reconsolidation-interference protocols aim to directly alter such traces by reactivating and destabilizing them before intervention. While this approach has shown benefits in fear, craving, and trauma-related symptoms, its application to depression remains untested. To our knowledge, this study provides the first experimental evidence of its utility in depression-like states. Sixty participants took part in a three-day, three-group, double-blind randomized controlled trial. On day one, helplessness was induced using a modified unsolvable anagram task. On day two, participants were randomized into three groups undergoing different interventions while completing another cognitive demanding task: (1) extinction, where participants experienced success from start to finish; (2) reconsolidation, where participants briefly reexperienced failure before succeeding; or (3) reactivation, where failure repeated. On day three, the helplessness task was presented again to evaluate susceptibility for recurrence across conditions. Behavioral, self-report, and EEG data were collected. Across test days, participants showed reduced motivation and performance, attributing failure to personal ability, confirming successful helplessness induction. However, interventions at day two produced no robust group differences on behavioral, self-report, or EEG measures. Exploratory analyses suggested that brain-derived neurotrophic factor (BDNF) levels may have mediated outcomes. Findings do not confirm reconsolidation-based behavioral interference as effective for depression-like helplessness. Nonetheless, exploratory results highlight BDNF as a potential mediator, warranting further study on its role in postretrieval extinction effects in depression. Show less

Psychological well-being among university students is often examined using variable-centered approaches that assume population homogeneity. Using Ryff's eudaimonic model and a person-centered analytic framework, this study examined latent profiles of psychological well-being among Ghanaian undergraduates, offering insight into how the Western-derived model functions in a non-Western cultural context. A cross-sectional design was employed to sample 574 regular undergraduate students from a public university in Ghana. Students completed the 18-item Ryff's Psychological Well-Being Scale. Latent profile analysis (LPA) followed by Chi-square tests were performed using JAMOVI statistical software. Four distinct profiles emerged: fully flourishing students (38.7%), harmonious life seekers (45.1%), purposeful self-actualizers (7.5%), and aspiring actualizers (8.7%). The profiles differed primarily in levels of autonomy, personal growth, and environmental mastery. Well-being profile membership was not associated with gender but varied significantly by age, although the effect size was small. The study findings suggest meaningful heterogeneity in eudaimonic well-being among Ghanaian undergraduates and highlight the importance of culturally sensitive, profile-based mental health interventions beyond demographic assumptions. Show less

Fetal growth restriction (FGR) remains a significant problem in obstetrics and is a key risk factor for perinatal brain injury. The fetal neuronal vesicles (FNVs) isolated from maternal blood represent an innovative approach-a "fetal brain liquid biopsy"-enabling early diagnostics of neuronal dysfunction in FGR. Western blotting was used to evaluate the protein pattern expression of FNVs isolated from the blood of pregnant women with FGR and uncomplicated pregnancy. Significant changes in the neurotrophic proteins levels (pro-BDNF, pro-NGF) and presynaptic neurotransmission proteins (SYN1, SYP, SYNPO) were identified. New data were obtained on changes in the expression of proteins of sumoylation (SUMO2/3/4) and neddylation (NAE1, UBC12), which differs in early-onset and late-onset FGR. Moreover, increased SUMO2/3/4 levels can be considered as an endogenous neuroprotective response to cerebral hemodynamic reaction in fetuses with late-onset growth restriction. An association has been established between changes in the expression of the studied proteins and intraventricular hemorrhage (IVH) in newborns with late-onset growth restriction. Show less

On the basis of life-style changes and statins, current guidelines recommend early combination therapy to reduce LDL cholesterol (LDL-C). Available and future novel non-statin lipid-lowering therapies may have specific advantages in patients with (1) statin intolerance, (2) elevated triglyceride-rich lipoproteins, (3) elevated lipoprotein(a), and (4) rare genetic dyslipidemias. Currently available treatment options to lower LDL-C with proven cardiovascular benefit include statins, ezetimibe, bempedoic acid, and PCSK9 antibodies. The 2025 update of the ESC/EAS dyslipidemia guidelines incorporates recommendations on early combination treatment and management of rare dyslipidemias, which are detailed in this review. Novel LDL-C-lowering strategies, targeting PCSK9 and CETP, may further improve dyslipidemia management. Drugs in development with profound effects on lipoprotein(a) or triglyceride concentration may allow for specific modification of residual cardiovascular risk. Innovative DNA-targeting therapies are moving towards clinical testing in larger studies. Various treatment options for patients with dyslipidemia and distinct characteristics have become available. Future developments may allow for even more tailored treatment, depending on dyslipidemia phenotype. Show less

This study was conducted to assess the clinical significance of programmed cell death-ligand 1 (PD-L1)-positive circulating tumor cells (CTCs) as predictive biomarkers for the efficacy of PD-(L)1 inhibitor-based treatment in advanced hepatocellular carcinoma (HCC). We enrolled 59 patients with unresectable HCC who received immunotherapy-based treatment and analyzed CTCs, PD-L1 CTCs were detected in 86.4% (51/59) of patients, with a PD-L1-positive rate of 83.7% (41/49). Compared with the "PD-L1 PD-L1 Show less

Astrocytes are central regulators of neural homeostasis, synaptic function, and neuroinflammatory responses in the central nervous system (CNS). Upon pathological stimuli, astrocytes undergo reactive transformations, producing pro-inflammatory cytokines, reactive oxygen species (ROS), and chemokines, which exacerbate neuronal injury. Flavonoids, a diverse class of polyphenolic compounds found in fruits, vegetables, and medicinal plants, have emerged as potent modulators of astrocyte activity, promoting neuroprotection and cognitive enhancement. These compounds, including quercetin, hesperetin, rutin, casticin, and anthocyanins, attenuate astrocyte-mediated neuroinflammation by suppressing NF-κB, MAPK, TLR, and NLRP3 inflammasome signaling while activating antioxidant pathways such as Nrf2 and PI3K/Akt. Flavonoid-mediated modulation also enhances the synthesis and release of neurotrophic factors, including BDNF, GDNF, NGF, and TGF-β1, which support synaptic plasticity, dendritic spine formation, and network connectivity. By preserving astrocytic homeostasis, reducing gliosis, and regulating astrocyte-microglia crosstalk, flavonoids mitigate cytokine-mediated neuronal damage, restore synaptic integrity, and improve learning and memory in models of neurodegeneration, ischemia, and neuroinflammation. Preclinical evidence suggests that flavonoids can cross the blood-brain barrier, exhibit low toxicity, and synergize with other neuroprotective interventions. Understanding the molecular mechanisms of flavonoid-astrocyte interactions provides insight into precision therapeutic strategies aimed at alleviating neuroinflammation and enhancing CNS resilience, offering promising avenues for the prevention and treatment of cognitive and neurodegenerative disorders. Show less