IntroductionPreterm birth is a major risk factor for disrupted brain development and subsequent neurodevelopmental disorders, yet the underlying mechanisms remain poorly understood. Further, typical neuroimaging analyses are particularly challenging in the neonatal brain: data is frequently low quality, and a lack of cellular development violates the assumptions relied on by many commonly-used techniques. In this study, we develop and present an advanced diffusion magnetic resonance imaging method to examine the microstructural organization of white matter in a clinically-acquired cohort of premature neonates.MethodsUsing a novel approach that resolves multiple tissue compartments within the brain, we provide highly detailed orientation and quantification of white matter fibers and tissue signal fraction. We also utilize a series of automated segmentation algorithms to identify and measure these metrics across key tracts and subcortical regions. We investigate how these measures relate to postmenstrual age, as well as to clinical factors reflecting neonatal illness severity.ResultsWe report successful segmentation and reconstruction of numerous white matter tracts throughout the neonatal brain. We further demonstrate the utility and functionality of microstructural analysis in a variety of pathologies commonly encountered in the neonatal clinical environment. Our results demonstrate tract-specific developmental trajectories, with early-maturing pathways showing higher microstructural organization. Exploratory analyses suggest that neonatal illness severity has modest, tissue-specific associations with microstructural properties.DiscussionThis work demonstrates that advanced microstructural imaging methods can extract meaningful white matter measurements from clinically-acquired scans, providing a practical framework for studying neonatal brain development in real-world hospital settings. These metrics are able to be calculated at extremely young ages, potentially allowing non-invasive study of vulnerable populations before detailed behavioral or neurological assessments are feasible.
Exploring ceramide as a novel biomarker and therapeutic target for Alzheimer’s disease
Metabolic dysregulation is increasingly being recognized as a hallmark across various neurodegenerative diseases. While Alzheimer’s disease (AD) is well-established as a dual proteinopathy characterized by amyloid-beta (Aβ) deposition and tau protein tangles, the specific mechanisms mediating lipid homeostasis imbalance have garnered increasing attention. However, translating these findings into safe clinical therapeutic targets remains a formidable challenge, primarily hindered by the pleiotropic roles of ceramides in maintaining neural and immune homeostasis, as well as the blood–brain barrier (BBB) penetration issues and systemic safety limitations of current sphingolipid-targeting strategies. We conducted a comprehensive search of electronic databases, including PubMed, Web of Science, and Google Scholar, to identify relevant studies published from database inception through March 2026. The search term combinations included: “Alzheimer’s disease,” “AD,” “ceramide,” “sphingolipid metabolism,” “biomarker,” “therapeutic target,” “neuroinflammation,” and “mitochondrial dysfunction.” To ensure the depth and rigor of this review, priority was given to peer-reviewed original research, systematic reviews, and meta-analyses. The search was restricted to English-language literature. Additionally, the reference lists of retrieved articles were manually screened to identify further relevant studies. This narrative review aims to comprehensively elucidate the potential roles of ceramides in AD pathogenesis, exploring their associations with triggering inflammatory responses, mediating apoptosis, interfering with signal transduction, and inducing mitochondrial dysfunction.
Personality functioning in adolescents with depression: links with childhood maltreatment, psychopathology, self-harm and suicidal ideation
BackgroundAdolescence represents a critical developmental period marked by significant vulnerability to depression, a condition with heterogeneous presentations that complicate clinical management. The co-occurrence of personality dysfunction with depression is known to indicate greater severity and poorer prognosis, yet specific features of this comorbidity in adolescent clinical samples require further delineation. This study aimed to compare clinical and psychosocial correlates in depressed adolescents with and without impaired personality functioning.MethodsThe clinical sample comprised 73 adolescents (aged 12–17; 83.6% female) diagnosed with depression or reporting clinically significant depressive symptoms. Participants completed self-report measures assessing personality functioning (LoPF-Q 12–18), childhood maltreatment (CEQ), psychopathology (YSR 11-18), mentalizing capacity (RFQY-8), borderline traits (BPFS-C), and self-harm behavior. Based on LoPF-Q 12-18 T-scores, participants were categorized into two subgroups: depression without personality dysfunction (T ≤ 64; n=20) and depression with personality dysfunction (T ≥ 65; n=53).ResultsResults indicated that adolescents with co-occurring depression and personality dysfunction exhibited significantly lower functioning across all personality domains compared to those with depression alone. This subgroup also reported an earlier onset and higher frequency of self-harm, more severe suicidal ideation, elevated borderline traits, and greater impairments in mentalizing. Furthermore, they demonstrated higher levels of internalizing, affective, conduct, and PTSD symptoms, alongside greater exposure to emotional neglect.ConclusionImpaired personality functioning in depressed adolescents is associated with elevated and multifaceted patterns of symptoms, including subjective distress and risky behaviors. These findings underscore the necessity of routinely assessing personality functioning in adolescents with clinically significant depressive symptoms to enable early identification and the development of tailored, integrated interventions for this high-risk subgroup.
Additive impulsivity and emotion dysregulation in adolescents with comorbid bipolar and substance use disorder: a cross-sectional factorial study
IntroductionComorbid bipolar disorder (BD) and substance use disorder (SUD) in adolescence is associated with poor clinical outcomes, yet the independent and interactive contributions of impulsivity and emotion dysregulation remain poorly understood.MethodsThis cross-sectional study employed a 2 × 2 factorial design to examine impulsivity, measured with the Barratt Impulsiveness Scale-11, and emotion regulation difficulties, measured with the Difficulties in Emotion Regulation Scale, across four groups of adolescents (N = 128; aged 12–18 years): BD+SUD (n = 32), BD-only (n = 32), SUD-only (n = 32), and healthy controls (n = 32). All clinical participants were assessed during euthymia. Factorial analyses of covariance controlled for age, sex, residence, family structure, and income.ResultsSignificant BD × SUD interactions were found for emotion regulation, F(1,120) = 35.89, p < .001, ηp2 = .230, and impulsivity, F(1,120) = 9.51, p = .002, ηp2 = .073. The BD+SUD group showed the highest scores on both measures, exceeding the SUD-only group by 38.90 points on emotion dysregulation and 26.72 points on impulsivity. In the substance-using subsample (n = 64), impulsivity was the strongest predictor of substance use severity (B = 0.61, p < .001; R2 = .48). The BD+SUD group also displayed earlier illness onset, mixed-feature predominance, greater polydrug use, and exclusive high-lethality suicide attempts. Low income was the strongest exploratory predictor of clinical group membership.DiscussionThese findings support an additive comorbidity model in which BD and SUD jointly amplify impulsivity and emotion dysregulation, and they highlight the need for integrated, impulsivity-focused interventions in adolescents with dual diagnoses.
Waiting between war and loss: a qualitative study on the experience of ambiguous loss among Syrian refugees
IntroductionAmbiguous loss refers to individuals’ lack of knowledge about the whereabouts or fate of loved ones due to traumatic events such as war or natural disasters. It is associated with significant economic, social, and psychological consequences, including grief, depression, and identity confusion.MethodsWe examined the psychological impact of ambiguous loss among 15 refugees displaced by the Syrian civil war. Participants (22 -53 years old; 9 women, 6 men) had experienced the disappearance or prolonged uncertainty regarding the fate of their spouse, child, sibling, or relative and had lived with uncertainty regarding the fate of their loved one for 4 to 13 years (in some cases, the uncertainty resolved after the interviews). We collected the data through semi-structured interviews and analyzed them using inductive thematic analysis.ResultsFindings revealed emotional oscillation between hope and hopelessness, social isolation, and difficulties adapting to changing roles. Although beliefs and collective rituals served as coping resources, inadequate support and stigma intensified distress.DiscussionThe results indicate that ambiguous loss is embedded in sociocultural contexts and underscore the need for culturally sensitive, family- and community-based psychosocial interventions and supportive national policies.
Family risk factors, dyadic coping, and family resilience in young stroke dyads: an actor-partner interdependence mediation model
ObjectiveStroke in young individuals constitutes a significant familial stressor, with ensuing family risk factors critically influencing recovery. While couples’ collaborative coping strategies play a vital role in enhancing family resilience, the mechanisms underlying this process remain largely unexplored. This study aims to elucidate the impact of familial risk factors and dyadic coping on the family resilience of young stroke.MethodsThis cross-sectional study integrates evidence-based research with clinical data. We developed a structured questionnaire grounded in identified familial risk factors. A cohort of 243 dyads, comprising young stroke patients and their spouses, was recruited from the neurology departments of four tertiary hospitals. The Actor–Partner Interdependence Mediation Model (APIMeM) framework was utilized, in which patients were treated as actors (influencing their own outcomes) and spouses as partners (influencing each other’s outcomes), to determine both direct and indirect effects among variables, with significance evaluated using bootstrap procedures (5,000 resamples, 95% confidence intervals). Model simplification was guided by chi-square difference testing.ResultsThe analysis indicated that family resilience could be strengthened in young stroke survivors and their spouses. APIMeM analyses showed that patients’ and spouses’ anxiety (β = –0.479, P = 0.002) and depression (β = –0.718, P < 0.001) had significant negative actor effects on their own family resilience, while patients’ activities of daily living (ADL) had significant positive actor (β = 0.175, P < 0.001) and partner effects (β = 0.198, P < 0.001) on family resilience. Crucially, dyadic coping partially mediated these relationships, with significant actor-actor indirect effects for anxiety (β =–0.139, 95% CI [–0.261, –0.029]), depression (β = –0.190, 95% CI [–0.321, –0.084]), and ADL (β = 0.062, 95% CI [0.009, 0.131]) on family resilience. Significant actor-partner mediation effects were also observed for depression (β = –0.072, 95% CI [–0.170, –0.017]) and ADL (β = 0.028, 95% CI [0.002, 0.079]).ConclusionsUsing a dyadic APIMeM approach, this study demonstrates that dyadic coping serves as a key mediator linking familial risk factors to family resilience in young stroke dyads. Resilience emerges as a shared, co-constructed process rather than an individual attribute, underscoring the need for interventions targeting the couple as a unit to mitigate intervention bias.
Diazepam combined with aripiprazole in the treatment of a catatonic stupor patient with venous thrombosis: a case report
BackgroundCatatonic stupor is a potentially life-threatening condition, with key symptoms including mutism, immobility, refusal to eat, and negativism. It may be accompanied by complications such as infection, hyperthermia, and thrombosis. When patients develop concurrent severe physical illnesses, this is very likely to cause delays in diagnosis and treatment, further increasing the risk of clinical deterioration.MethodsThis article reports a 52-year-old patient with schizophrenia presenting with catatonic stupor and failure to establish effective communication. The uniqueness of this case is that the patient was admitted with concurrent pulmonary infection, pulmonary embolism, and lower limb deep venous thrombosis, and modified electroconvulsive therapy (MECT) was associated with substantial clinical risks. The patient was eventually treated with a combination of diazepam and aripiprazole. During treatment, the severity of the patient’s catatonic symptoms was assessed using the Bush-Francis Catatonia Rating Scale (BFCRS).ResultAfter combined treatment with diazepam and aripiprazole, the patient’s catatonic symptoms were relieved, and various functions gradually recovered. The BFCRS score reduction rate exceeded 70%, indicating that the expected therapeutic effect was achieved.ConclusionAs a relatively safe and effective intervention regimen, the combination treatment of diazepam and aripiprazole may be applicable to high-risk catatonic patients with relative contraindications to MECT, such as those complicated with venous thrombosis, providing a new therapeutic option for catatonic stupor.
Multiplexed, precise genome engineering in monocots with twin prime editing systems
Nature Biotechnology, Published online: 05 June 2026; doi:10.1038/s41587-026-03174-5
Plant genome editing is multiplexed with twin prime editing.
Structural motif search across the protein universe with Folddisco
Nature Biotechnology, Published online: 05 June 2026; doi:10.1038/s41587-026-03162-9
Folddisco enables protein structural motif search in million scale databases.
Data guardian seeks clarification on Palantir patient data access
The National Data Guardian has asked NHSE to explain how Palantir staff gained access to patient data in the FDP, something it was unaware of.