BackgroundIntravenous thrombolysis with alteplase remains the standard reperfusion strategy for acute ischemic stroke (AIS), yet many patients still experience unfavorable outcomes despite timely treatment, underscoring the need for reliable multimodal prognostic markers.ObjectiveTo identify independent clinical, laboratory, and neuroimaging predictors of unfavorable 3-month functional outcome in anterior circulation AIS treated with alteplase, and to develop, internally validate, and benchmark an integrated multivariable model in accordance with TRIPOD.MethodsThis prospective single-center cohort study enrolled 268 consecutive patients with anterior circulation AIS receiving intravenous alteplase within 4.5 h of symptom onset (March 2022–February 2025). Three-month outcome was assessed by the modified Rankin Scale (mRS 0–2 favorable; 3–6 unfavorable) using validated structured instruments administered by blinded raters. Multivariable logistic regression was performed, and the final model was internally validated by 1,000-replicate bootstrap with optimism correction and shrinkage, evaluated by decision curve analysis (DCA), rendered into a nomogram, and benchmarked head-to-head against three previously published reference models using the DeLong test.ResultsOf 268 patients, 99 (36.9%) experienced unfavorable outcomes. Seven independent predictors were identified: early neurological deterioration (adjusted OR 3.45, 95% CI 2.01–5.92), large infarction exceeding one-third of the middle cerebral artery territory (OR 2.78, 1.58–4.89), baseline NIHSS (OR 1.14 per point, 1.07–1.22), poor Tan collateral score (OR 2.31, 1.34–3.98), low clot burden score (OR 2.15, 1.28–3.61), elevated D-dimer (OR 2.19, 1.29–3.72), and elevated CRP (OR 1.87, 1.11–3.15). The model achieved an apparent AUC of 0.847 (95% CI 0.801–0.893) and an optimism-corrected AUC of 0.831 (0.785–0.877) on bootstrap validation, with satisfactory calibration (Hosmer–Lemeshow P = 0.394). DCA showed positive net benefit across threshold probabilities of 0.15–0.75, and the model exceeded the recalibrated Hu, Ping, and Lv models.ConclusionA multimodal panel integrating clinical, inflammatory, coagulation, and neuroimaging parameters independently predicts unfavorable 3-month outcome following intravenous thrombolysis in anterior circulation AIS. The findings are hypothesis-generating pending external validation in independent multicenter cohorts.
Neonatal propofol exposure impairs synaptic plasticity and cognition, associated with BAG3 upregulation and disrupted synaptic protein homeostasis
BackgroundPropofol is widely used in pediatric anesthesia, but it has been implicated in adverse effects on brain development following repeated early-life exposure. Bag3, a co-chaperone protein involved in proteostasis and the neuronal stress response, may play a critical role in regulating synaptic function during early brain maturation.MethodsNeonatal mice were treated with propofol on postnatal days 5–7. Hippocampal neurogenesis was assessed via BrdU immunofluorescence. Synaptic proteins (PSD95, SNAP25) and Bag3 expression were measured by Western blotting. Behavioral performance in adolescence was evaluated using open-field, elevated plus-maze, Morris water maze, Y-maze, and T-maze tests.ResultsPropofol exposure significantly reduced proliferative activity (BrdU incorporation) in the dentate gyrus and decreased PSD95 and SNAP25 expression in both the cortex and hippocampus. Bag3 expression was markedly upregulated, accompanied by a mild increase in its phosphorylated form. Behaviorally, propofol-treated mice showed anxiety-like behavior and impairments in spatial learning and working memory.ConclusionThese findings suggest that early-life exposure to propofol impairs neurogenesis and synaptic plasticity. This process is temporally associated with the upregulation of stress-responsive co-chaperone BAG3, which precedes the of synaptic protein homeostasis. While causal relationship remains to be established, these findings identifies BAG3 as a candidate correlative marker of anesthetic-induced neurotoxicity and highlights it as a target for future mechanistic studies.
Integrated multi-omics and deep learning analysis reveals neurotransmitter metabolism regulatory mechanisms of Tianwang Buxin Dan
BackgroundTianwang Buxin Dan is a classical Traditional Chinese Medicine formula with documented clinical use in treating neuropsychiatric disorders, yet its molecular mechanisms remain incompletely understood.MethodsWe developed an integrated analytical framework combining transcriptomic and metabolomic profiling with deep learning to investigate the neurotransmitter metabolism regulatory mechanisms of Tianwang Buxin Dan. Data were collected from a para-chlorophenylalanine (PCPA)- induced insomnia rat model following formula intervention. A multi-omics feature fusion strategy incorporating autoencoder-based dimensionality reduction and cross-modal attention mechanisms was implemented to address data heterogeneity.ResultsA total of 1,847 differentially expressed genes and 286 differential metabolites were identified. The constructed deep neural network achieved 91.2% classification accuracy with an AUC of 0.956 in five-fold cross-validation, and permutation testing confirmed that performance was significantly above chance (p < 0.001). Ablation experiments demonstrated that integrated multiomics outperformed single-omics models. Tryptophan hydroxylase 2 (TPH2) upregulation and monoamine oxidase A (MAO-A) suppression were identified as key features and partially validated by qPCR and Western blot.DiscussionTianwang Buxin Dan may modulate neurotransmitter metabolism through coordinated regulation of biosynthetic and catabolic pathways. A component-target-pathway regulatory network identified 47 key molecular targets interconnected through 156 functional associations. This work provides a computational framework applicable to mechanism studies of other compound TCM formulations.
Cerebrospinal fluid mechanics across CNS barriers: from production, circulation, and clearance to mechanomedicine
BackgroundCerebrospinal fluid (CSF) is often framed as a transport medium, yet its motion and pressure dynamics impose continuous mechanical loading on central nervous system (CNS) barrier and interface systems. These cues span scales—from cilia-scale near-wall shear to craniospinal compliance-driven pulsatility—and may shape barrier phenotypes, immune programs, and clearance efficiency. In simple terms, this review asks how abnormal CSF motion is converted into barrier dysfunction and disease-relevant outcomes.Main bodyWe synthesize evidence that CSF mechanics is spatially heterogeneous along the production-to-outflow axis and is sensed by specialized mechanotransduction modules in choroid plexus epithelium, ventricular ependyma, perivascular astrocytic endfeet/neurovascular unit, and meningeal outflow/lymphatic pathways. We discuss how shear, pulsatile forcing, and pressure–compliance relationships interact with mechanosensitive ion/transport channels, ciliary polarity, glycocalyx–ECM/FAK signaling, junctional remodeling, and nuclear mechanotransduction to regulate permeability and immune–metabolic states. We highlight quantitative toolkits, including low-velocity 4D flow MRI, phase-contrast MRI, waveform metrics, microfluidic barrier platforms, and computational modeling, that enable mapping of patient-relevant mechanics to cell-level exposures. Disease sections emphasize mechanical failure modes: oscillatory overload and multi-site CSF–barrier disruption in hydrocephalus; loss of effective pulsatile transfer and impaired perivascular exchange in neurodegeneration; age-related stiffening and altered mechanosensitivity across barriers; meningeal outflow dysfunction with neuroinflammatory amplification; and acute mechanical disruption after trauma.ConclusionWe propose a mechanomedicine framework for CSF–barrier coupling that prioritizes measurable mechanical exposures, interface-specific mechanosensors, and actionable endpoints, including barrier state, permeability, immune trafficking, and imaging-derived coupling metrics. This framework supports closed-loop translational pipelines linking human phenotyping to mechanistically calibrated models and may guide strategies that modulate CSF dynamics or target mechanotransduction nodes with quantifiable outcomes.
Automated diagnosis of Sturge–Weber syndrome by detecting leptomeningeal angiomatosis from MRI using a multi-task deep learning framework
ObjectivesSturge–Weber Syndrome (SWS) is a rare neurocutaneous disorder requiring early and accurate diagnosis. This study aims to develop a deep learning framework for automatic diagnosis of SWS by detecting leptomeningeal angiomatosis (LA) in brain magnetic resonance images (MRI).MethodsThis retrospective study includes 40 SWS patients and 101 healthy controls. T1-weighted MRI were collected over 15 years with different scanners. Multi-scale harmonization was proposed to normalize the images to uniform mean and standard deviation. We developed a deep learning model based on the UNet framework with convolutional neural networks and transformer. A multi-task pipeline was designed to perform LA segmentation and SWS classification. The model was pre-trained on a public dataset and fine-tuned and tested on our dataset using a 5-fold cross validation. The segmentation and classification results were compared with the ground truth and human readers using various metrics at the voxel and LA level.ResultsFor LA segmentation, our model achieved overall Dice, voxel-level sensitivity, specificity, accuracy, and kappa of 0.768, 0.772, 0.992, 0.983, and 0.760, respectively. The LA volume segmented by our model showed a high agreement and consistency with the ground truth, outperforming the human readers. For SWS classification, our model achieved sensitivity, specificity, accuracy, and AUC of 0.974, 1.000, 0.993, and 0.998, respectively.ConclusionWe developed a multi-task learning framework for automated LA segmentation and SWS classification. This single-center proof-of-concept study shows promising performance in both tasks. External validation may boost the clinical application of the developed model, assisting less-experienced neurologists for improved SWS diagnosis.
Knowledge, attitudes, and perception toward new psychoactive substances among Saudi university students: a cross-sectional study
BackgroundNew psychoactive substances (NPS) are defined as chemical compounds that are synthesized or extracted from natural sources with the aim of producing psychoactive effects similar to those produced by controlled substances but not regulated under current legislation. Worldwide, the rise in the use of NPS has been outpacing regulation and education efforts, leading to substantial health risks, especially for the young adults’ population. In Saudi Arabia, substance-use prevention is supported through the Saudi 2030 initiative led by the Ministry of Interior and National Committee for Narcotics Control; nonetheless, most studies conducted at the national level have centered on traditional drugs only.ObjectivesThe purpose of this research was to evaluate the knowledge, attitude, and perception related to NPS among King Faisal University students, and to determine the predictors of better knowledge and permissive attitude.MethodsA cross-sectional study was conducted with 300 students via an anonymous web-based survey questionnaire to assess sociodemographic characteristics and knowledge, attitude, and perception measures. Ethical approval was obtained from King Faisal University (reference no. KFU-REC-2026-MAR-ETHICS4051) on the 12th of March 2025. Chi-squared test/Fisher’s exact test were applied to understand the relationship between sociodemographic variables and level of knowledge, and independent samples t-test/ANOVA for comparison of mean attitude scores. Logistic regression analysis was conducted to identify independent predictors of high knowledge and permissive beliefs.ResultsOut of the respondents (74% females, mean age 18–24 years), (58%) had high levels of knowledge regarding NPS. Access to NPS was easy for (57%), mostly through online media (70.8%) and past usage of NPS was admitted by (39.7%). Significantly greater knowledge regarding NPS was shown by females compared to males (64.0% vs 41.0%; P<0.001), while being male predicted poor knowledge (AOR = 0.407, 95% CI:0.229–0.722, P = 0.002). Prior NPS use (AOR = 2.502, 95% CI:1.209–5.176, P = 0.013) and easy access (AOR = 2.298, 95% CI:1.233–4.285, P = 0.009) independently predicted permissive beliefs. Common use motivations included social gatherings (47.9%), weight loss (40.3%), and stress reduction (37.0%).ConclusionsStudents have moderate to high levels of knowledge, their attitudes towards NPS were significantly influenced by ease of access on the Internet and previous usage experience. This indicates the necessity of educational measures to tackle the increasing threat posed by NPS to Saudi universities.
Increasing familial engagement in family violence services: a systematically conducted realist review of barriers and facilitators
PurposePhysical, emotional, and sexual violence and abuse occurring between close or extended family members are forms of family violence (FV). The negative impacts of FV are diverse, numerous, and pervasive for all individuals involved. To effectively support individuals experiencing FV, services designed to reduce and prevent FV and its associated harms must maintain participant engagement. Therefore, the purpose of this realist review was to synthesize literature on barriers and facilitators to individuals’ engagement in FV services so that relevant strategies can be implemented to improve service effectiveness.MethodsThis realist review was conducted systematically and searched five databases up to August 2024, screening 1, 334 evidence sources. Findings were examined in relation to families and parents, including mothers, fathers, and children, and were supplemented by relevant service provider perspectives.ResultsMost findings from the 24 included studies focused on facilitators of engagement. Priming and introductory sessions, provider-family rapport, group formats, empathy, trustworthiness, and family-centred approaches that consider familial needs and goals were identified as important facilitators of engagement in FV services. Prominent barriers included socioeconomic challenges, competing demands, childcare responsibilities, inadequate provider-client rapport, limited accessibility, intense initial meetings, and long service duration.ConclusionsRooted in family-centred approaches and interagency collaboration, recommended strategies to improve family engagement in FV services focus on opportunities during service: 1) intake; 2) initiation; and 3) delivery. These strategies are described in relation to context (e.g., socioeconomic factors) and potential mechanisms (e.g., perceived cultural safety), and could be further evaluated using implementation science methods to optimize family engagement in FV services.
Power without limits: exploring emotional regulation, moral authority, and psychiatric overreach through the Wizarding World of Harry Potter
BackgroundPsychiatry has never had more tools to relieve psychological suffering. Psychopharmacology, neuromodulation, early intervention, digital monitoring, and preventive approaches have expanded what clinicians can do. Yet this growing technical capacity also raises an uneasy question: when does care become control? Cultural narratives can offer spaces for examining such tensions, particularly when they dramatize power, vulnerability, suffering, and moral authority.AimThis narrative review uses the Wizarding World of Harry Potter as a conceptual lens to examine emotional regulation, moral authority, and psychiatric overreach, focusing on two contrasting figures: Lord Voldemort and Isidora Morganach.MethodsA theory-informed narrative review was conducted using a concept-focused analytic framework and structured conceptual synthesis. Literature was identified through focused searches in PubMed, PsycINFO, Scopus, and Google Scholar from database inception to June 2026, complemented by backward reference tracking. Sources covered Harry Potter scholarship, emotional regulation, psychological flexibility, narcissism and Dark Triad traits, medicalization, overdiagnosis, clinical ethics, and narrative medicine. To improve transparency, the synthesis distinguished direct literature on the Wizarding World from indirect psychiatric, psychological, ethical, and medical humanities scholarship used for conceptual interpretation.ResultsTwo pathways to psychiatric overreach and an intermediate zone of proportionate care were identified. The first, represented by Voldemort, involves destructive domination, emotional suppression, denial of vulnerability, instrumental use of others, and coercive authority. The second, represented by Isidora Morganach, involves hyper-compassionate control, intolerance of suffering, elimination of negative affect, moral certainty, and paternalistic intervention. Between these extremes, the intermediate zone emphasizes emotional integration, psychological flexibility, shared decision-making, contextual judgment, ethical proportionality, and clinical humility. Although one pathway is cruel and the other compassionate, both illustrate power exercised without sufficient emotional integration or ethical restraint.ConclusionBy exploring psychiatric questions through the Wizarding World, this review highlights how narrative frameworks can clarify the ethical boundaries of intervention. The central lesson is not that intervention is dangerous, but that intervention must remain proportionate, reflective, and ethically bounded. Psychiatry’s task is not to abolish all distress, but to relieve suffering while preserving autonomy, meaning, and human vulnerability.
Memory-focused therapy: an integrated intervention to reduce trauma symptoms, maladaptive cognitive processes, and emotional distress in Afghan youth
BackgroundAfghan youth continue to face chronic war-related trauma, terrorist violence, and severe disruptions to education and social support systems, resulting in high rates of posttraumatic stress disorder (PTSD), depression, anxiety, and hopelessness. There is a critical need for culturally responsive, low-intensity, and feasible psychological interventions that can be delivered in low-resource and unstable settings.ObjectiveThis study conducted a preliminary evaluation of the efficacy, acceptability, and mechanisms of change associated with Memory-Focused Therapy (MFT), an integrative intervention targeting autobiographical memory processing, acceptance-based regulation, and future self-construction among youth affected by the Kaaj Education Center attack in Kabul, Afghanistan.MethodsA single-group repeated-measures design was used with 26 participants assessed at baseline, post-intervention, and three-month follow-up. Standardized measures of PTSD, depression, anxiety, stress, cognitive avoidance, cognitive fusion, resilience, and posttraumatic growth were administered. MFT was delivered in 12 structured group sessions. Additionally, qualitative data from semi-structured interviews and therapist field notes were analyzed using thematic analysis.ResultsQuantitative analyses showed significant reductions in PTSD symptoms, depression, anxiety, stress, cognitive avoidance, and cognitive fusion from baseline to post-intervention, alongside significant increases in posttraumatic growth. Several of these improvements were maintained at follow-up. Qualitative findings reflected four overarching themes: (1) facilitator experiences and implementation challenges in high-risk contexts, (2) improvements in cognitive and emotional processing, (3) growth in meaning, relationships, values, and future orientation, and (4) exposure to traumatic memories and reduced avoidance.ConclusionFindings provide preliminary evidence that MFT is a feasible, acceptable, and potentially effective intervention for trauma-affected Afghan youth. By integrating trauma memory processing, present-moment emotional regulation, and future-oriented meaning-making, MFT appears to support improvements in psychological coherence, self-continuity, and resilience. Further controlled and longitudinal studies are needed to confirm these effects and examine underlying mechanisms.
Parental broad autism phenotype traits and executive function in families of children with autism spectrum disorder
BackgroundParents of children with autism spectrum disorder (ASD) frequently exhibit subclinical Broad Autism Phenotype (BAP) traits, though their relationship with executive function (EF) remains underexplored. This study investigated associations between parental BAP traits and their EF performance.MethodsThe Broad Autism Phenotype Questionnaire (BAPQ) was used to assess the BAP traits in parents of children with ASD and parents of healthy children. Among them 20 of the high-BAP ASD parents with a total BAPQ score exceeding 3.55 and 20 of the parents of typically developing children completed executive function tests. The researchers utilized the flanker, 2-back, and Task-switching paradigm to examine their EF. Correlations analysis was used to analyze BAP-EF relationships.ResultsThe self-reported questionnaires indicated that parents of children with ASD had significantly higher BAPQ scores than non-ASD’s parents, with fathers scoring 41.21% versus 15% (χ2 = 31.628, p < 0.01), and mothers 26.25% versus 8.37% (χ2 = 25.764, p < 0.01). Parents of ASD children exhibited significantly prolonged reaction times on the Flanker task (528.95 ± 78.90 ms vs. 426.80 ± 18.40 ms, T = 15.639, p<0.01), with BAPQ total scores positively correlating with slower responses (R² = 0.2325, p = 0.0313). Paradoxically, they demonstrated accelerated 2-Back incongruent reaction times (537.60 ± 80.21 ms vs. 665.70 ± 137.17 ms, T = 6.715, p=0.001) but reduced accuracy (0.947 ± 0.037 vs. 0.983 ± 0.016, T = 16.875, p<0.01), where BAPQ again correlated with reaction times (R² = 0.2318, p = 0.0316). Crucially, these associations were absent in controls, and BAPQ scores showed no relationship with task accuracy in either group.ConclusionsBAP traits are associated with attentional control challenges (indexed by Flanker Task) and a maladaptive speed-accuracy tradeoffs during working memory demands.