BackgroundAcute branch atheromatous disease (BAD) is one of the leading contributors to morbidity and disability in Asia, and early neurological deterioration (END) is common in affected patients. This study aimed to establish machine learning models to predict the risk of END in patients without reperfusion therapy.MethodsPatients with acute BAD who did not receive reperfusion therapy were retrospectively enrolled. Core predictive features were selected by LASSO regression with bootstrap stability assessment, and we used seven machine learning algorithms to build models. XGBoost was selected based on validation performance, nested cross-validation, and 1,000-iteration bootstrap validation. A spline logistic regression model served as the non-linear baseline. SHAP analysis was used to explain the model and develop a simple scoring system. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC), and clinical utility was evaluated using decision curve analysis (DCA).ResultsA total of 369 patients were included in our research. We screened predictive factors with LASSO regression and ultimately identified five key variables. These included maximum infarct area, lactate dehydrogenase (LDH), number of infarct slices, admission systolic blood pressure (SBP), and neutrophil count. The XGBoost model achieved the best overall performance, with AUC of 0.927 in the training set and 0.846 in the validation set. Nested cross-validation yielded an unbiased AUC of 0.866 (95% CI: 0.817–0.925), and bootstrap validation produced a mean OOB AUC of 0.855 (95% CI: 0.760–0.941). The scoring system stratified patients into low (0–6 points), intermediate (7–13 points), and high (14–20 points) risk groups. DCA demonstrated favorable clinical utility. SHAP analysis also indicated that maximum infarct area and LDH were the top two predictors of END.ConclusionAn XGBoost-based prediction model and a simple scoring system, integrating maximum infarct area, LDH, number of infarct slices, admission SBP, and neutrophil count, provide reliable END risk prediction for acute BAD patients without reperfusion therapy.
A high-dimensional atlas of parvalbumin interneuron soma morphology in mouse visual and somatosensory cortex
Parvalbumin-positive (PV+) inhibitory interneurons are central components of experience-dependent plasticity in the visual cortex (V1). Anatomically, they are distributed across cortical layers and are traditionally classified as basket, chandelier, or bipolar cells based on dendritic and axonal arborization patterns. In parallel, physiological, transcriptomic, connectomic, and multimodal studies have revealed substantial diversity within PV+ populations, raising the question of how this diversity is organized within cortical circuits. In contrast, light microscopy studies based on soma labeling have primarily quantified PV+ cells using size and density, and the potential of soma morphology to capture this diverse organization remains unclear. To address this, we developed a high-throughput, data-driven approach to quantify PV+ soma morphology in > 14,000 cells from mouse V1 and somatosensory cortex (S1). Using 97 morphological features combined with clustering, phenotyping, and laminar mapping, we identified structured diversity in PV+ somas. PV+ cells were organized into 13 morphological clusters along partially independent gradients of size and shape. Phenotyping identified four size and five shape categories that describe PV+ cell diversity across cortical areas. Mapping these categories onto cortical layers revealed a structured organization in which specific morphologies are enriched within distinct laminar compartments. This organization aligns with cortical architecture and suggests that PV+ interneuron morphology is systematically related to circuit structure. These findings demonstrate that substantial morphological information can be extracted from standard PV+ labeling approaches using quantitative analysis. Together, this work provides a high-dimensional atlas of PV+ interneuron soma morphology in mouse V1 and S1 and establishes a framework for linking cellular anatomy to circuit organization and experience-dependent plasticity.
Longitudinal changes in MMN and P3 during emotional processing in adolescents who engage in NSSI: a 12-week follow-up study
BackgroundAdolescents with nonsuicidal self-injury (NSSI) often show deficits in negative emotion regulation. Within the dual-process framework of implicit and explicit emotion regulation, these deficits may reflect an automatic bias toward negative information and insufficient later-stage controlled regulation. Whether routine clinical intervention modifies both early automatic detection and later controlled evaluation of negative emotional information remains unclear.MethodsIn a longitudinal sample of 32 adolescents with NSSI, we examined changes in mismatch negativity (MMN) and P3 components elicited during an emotional oddball task before and after a 12-week clinical intervention. At baseline and Week 12, participants completed clinical assessments and a two-choice visual emotional oddball task containing neutral standards and negative, positive, and neutral deviants while EEG was recorded. MMN (Fz, 240–300 ms) and P3 (Pz, 450–650 ms) amplitudes were derived from deviant-minus-standard difference waves, indexing pre-attentive deviance detection and controlled evaluation, respectively.ResultsThe intervention selectively modulated neurocognitive processing of negative deviants. Self-injury ideation days (p = .036) and NSSI episode frequency (p = .007) both significantly decreased. MMN absolute amplitude to negative stimuli decreased significantly (p = .047), suggesting attenuated automatic salience detection, whereas P3 amplitude to negative stimuli increased significantly (p = .027), indicating enhanced controlled evaluation. Responses to positive and neutral conditions and behavioural performance remained stable. No baseline ERP–clinical correlations emerged; post-intervention, NSSI ideation days correlated with positive P3 (r = 0.380, p = .032), and episode frequency with neutral P3 (r = 0.461, p = .008).ConclusionsA 12-week intervention may attenuate automatic negative bias while enhancing controlled evaluative processing in adolescents with NSSI, consistent with the implicit–explicit framework. MMN and P3 may serve as candidate biomarkers and temporally sensitive tools for tracking intervention response when behavioural performance is stable.
Case Report: Reintroduction of winged infusion sets to needle syringe programs – advancing equity in harm reduction
BackgroundIn January 2023, following a 20-year ban, the New South Wales (NSW) Needle and Syringe Program (NSP) Guidelines permitted NSPs to provide winged infusion sets (‘butterflies’) and larger-volume syringes (‘barrels’) commonly used for injecting methadone liquid intravenously.ApproachThe Kirketon Road Centre (KRC) integrated the distribution of ‘butterflies and barrels’ (referred to as ‘butterfly packs’) into its service delivery in April 2023 and developed resources in collaboration with the Uniting Medically Supervised Injecting Centre (MSIC) and the NSW Users and AIDS Association (NUAA). This case report presents an audit of service delivery and self-reported client outcomes following the introduction of ‘butterfly packs’.OutcomesSince April 2023, KRC has been consistently supplying ‘barrels’ and ‘butterflies’ to clients who inject methadone. The proportion of NSP visits by clients who reported methadone as the last drug injected increased significantly after the program’s introduction (from 2.2 to 4.0 methadone-related attendances per month), and so did the amount of corresponding injecting equipment and verbal education sessions. Among 18 survey respondents, the majority reported improved health or safety since accessing butterfly packs (89%).ConclusionEquipment for intravenous methadone administration can be safely and efficiently distributed by NSP programs. Access to harm reduction services should be based on vulnerability and need, with services tailored accordingly. The policy reversal allowing ‘butterflies and barrels’ and service innovations such as KRC’s program have addressed a longstanding gap, advancing equity in harm reduction for people who inject methadone in NSW.
Tracking the longitudinal course of physiologic and mental health functioning among individuals in substance use disorder treatment
IntroductionMental health monitoring is crucial to long-term recovery in substance use disorder (SUD) treatment; however, little is known about how changes in physiological indicators align with changes in self-reported mental health over time.MethodsWe examined longitudinal associations of resting heart rate (RHR) and heart rate variability (HRV) collected via a WHOOP® photoplethysmography device with self-reported stress, anxiety, and depressive symptoms among individuals in SUD treatment. Participants (N = 59) continuously wore the device and completed at least two mental health and stress assessments during the first month of residential treatment. ResultsLinear regression results indicated favorable changes in mental health and/or physiologic metrics, with notable heterogeneity in concurrent subject-level trends. Among participants with decreased RHR (better physiological functioning), 39% (N=23) also endorsed decreased stress, 42% (N=25) decreased anxiety, and 39% (N=23) improved depressive symptoms. Of those with increased HRV (greater stress adaptability), 39% (N=23) endorsed decreased stress, 39% (N=23) improved anxiety, and 41% (N=24) reduced depressive symptoms.DiscussionConcurrent changes in physiologic and mental health metrics during the first month of treatment varied across participants. These findings highlight the importance of integrating subjective mental health measures with physiological indicators to capture clinically relevant change during early SUD treatment.
The therapeutic role of self-transcendence in moral injury recovery: theory, mechanisms, and clinical implications
A growing body of psychological and neuroscientific research suggests that moral injury (MI) involves maladaptive self-referential processing, including disruptions in moral identity, rigid negative self-appraisals, and impaired meaning-making following exposure to potentially morally injurious events (PMIEs). Building on Mindfulness-to-Meaning Theory (MMT), this paper proposes self-transcendence (ST)—a metacognitive state characterized by reduced self-focus, expanded awareness, transcendent affect, and prosocial meaning—as a potential mechanism for MI recovery. Within MMT, mindfulness practice is theorized to cultivate ST via decentering and meta-awareness, processes that broaden attentional scope, promote flexible cognitive reappraisal, and modulate habitual self-referential processing. Mindfulness and contemplative research further link ST to increased cognitive flexibility, reduced in shame-focused narrative self-processing, and adaptive integration of emotionally and morally disruptive experiences. Drawing on an integrative review of ST-consistent and MI-related mechanisms, this paper argues that fostering ST through mindfulness-based and contemplative practices may reduce rigid self-focus, expand interpretive frameworks of meaning, and support moral identity repair and meaning-making. Implications are discussed for designing interventions that intentionally cultivate ST as both standalone approaches and modular components, while acknowledging current limitations in measurement, readiness assessment, and the reliable induction of ST states.
Association between plasma proBDNF levels and cognitive impairment in patients with alcohol dependence: a case–control and longitudinal study
BackgroundAlcohol dependence is frequently accompanied by cognitive impairment. Brain-derived neurotrophic factor (BDNF) signaling plays a critical role in synaptic plasticity, while the precursor form, proBDNF, has been increasingly implicated in neurodegenerative and psychiatric disorders. However, the association between plasma proBDNF levels and cognitive impairment in alcohol dependence remains unclear.MethodsEighty male patients with alcohol dependence and forty-two matched healthy controls were enrolled. Plasma proBDNF levels were measured via enzyme-linked immunosorbent assay (ELISA). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Modified Wisconsin Card Sorting Test (M-WCST), and the Verbal Fluency Test (VFT). Forty-one patients were reassessed after four weeks of abstinence. Group comparisons and correlation analyses were performed.ResultsPatients with alcohol dependence exhibited significantly elevated plasma proBDNF levels and impaired cognitive performance compared with controls. Plasma proBDNF levels were positively correlated with alcohol consumption severity, and linked to global cognitive deficits alongside nuanced executive performance variations. After four weeks of abstinence, plasma proBDNF levels decreased and cognitive performance improved; however, changes in proBDNF were weakly associated with cognitive recovery.ConclusionsElevated plasma proBDNF levels are associated with alcohol dependence severity and cognitive impairment, suggesting that proBDNF may serve as a peripheral biomarker reflecting the dynamic neurocognitive status in alcohol dependence.
Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial
Nature Medicine, Published online: 10 June 2026; doi:10.1038/s41591-026-04436-0
Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.
Brain Health for Economic Resilience: a data-driven framework for the brain-positive economic transition
Nature Medicine, Published online: 10 June 2026; doi:10.1038/s41591-026-04444-0
Announced in this Comment and in collaboration with Nature Medicine is the convening of the Brain Health for Economic Resilience Commission, a global, transdisciplinary effort to define, measure and operationalize brain health and cognitive capacity as foundational drivers of economic resilience.
Cerebellar aging is spatially heterogeneous and supports cognitive resilience in later life
Nature Neuroscience, Published online: 10 June 2026; doi:10.1038/s41593-026-02289-x
The cerebellum ages unevenly, with some regions showing preservation that may help protect the brain from decline. The authors show that large cerebellar volume is associated with stronger cognitive resilience in healthy aging and Alzheimer’s disease.