IntroductionAlthough vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy, its mechanisms of action remain unresolved, resulting in variable clinical efficacy. Given the strong anatomical and functional coupling between vagal afferents and the locus coeruleus–noradrenergic system, this study investigated whether VNS directly impacts an electrophysiological marker of this system, the P3b event-related potential, and how such modulation relates to therapeutic outcomes.MethodsFifteen adults who had undergone long-term VNS implantation performed an auditory oddball task with the device disabled (OFF) and enabled (ON), with ON separated into electrical pulse-train (ON HIGH) and inter-burst break (ON LOW) phases to investigate the direct impact of electrical stimulation on the P3b.ResultsLinear mixed-effects modelling revealed a significant interaction between VNS condition and clinical response: responders showed reduced P3b amplitude (p = 0.023) and prolonged latency during ON (p = 0.007), whereas non-responders exhibited increased amplitude (p = 0.009) and trending shortened latency (p = 0.078). These VNS-induced changes correlated monotonically with a continuous clinical response score (r_amplitude = −0.62, r_latency = 0.48). In addition, a simple classification approach based on a composite amplitude-to-latency index was included to illustrate the potential of P3b modulation as a biomarker for distinguishing responders from non-responders, showing an overall accuracy of 86.7%. No pulse-locked modulation was observed between ON HIGH and ON LOW.DiscussionThese findings demonstrate that VNS elicits group-specific acute effects on cognitive–electrophysiological markers and support P3b modulation as a promising biomarker for predicting therapeutic efficacy.
Transformer-based fusion of radiomics-habitat and deep learning for assessing unruptured intracranial aneurysm instability
ObjectivesTo develop and validate a prediction model that integrates radiomics-habitat and deep learning (DL) features derived from vessel wall MRI (VWI) for evaluating unruptured intracranial aneurysms (UIAs) instability.MethodsFirst, from January 2022 to January 2024, 519 consecutive patients with suspected UIAs were screened. After applying exclusion criteria, 293 patients with 312 UIAs were ultimately enrolled. 197 UIAs were stable (from 188 patients) and 115 UIAs were unstable (from 105 patients). Second, aneurysm regions were segmented, and K-means clustering was used to partition them into three habitat subregions. Third, a Transformer-based fusion model for assessing UIA instability was developed to integrate radiomics-habitat features, DL features, and clinical variables. Model performance was evaluated using AUC, calibration curves, and clinical gain metrics, including Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI). Last, SHAP (SHapley Additive exPlanations) was applied to enhance model interpretability.ResultsThe Transformer-based fusion model assessing UIA instability exhibited superior performance (validation AUC = 0.844) compared with the optimal radiomics-habitat model (AUC = 0.721) and the top-performing DL model (DenseNet169, AUC = 0.816). The model demonstrated superior clinical utility, with an NRI of 0.282 and an IDI of 0.558 compared to the Radiomics-Habitat model. Decision curve analysis showed a high net clinical benefit across a range of threshold probabilities.ConclusionThe Transformer-based fusion model provides an exploratory risk-assessment model and has the potential to assist in clinical decision-making.
The relationship between healthy sleep patterns and the risk of scoliosis: a large prospective cohort study
BackgroundCurrently, prospective evidence on how sleep habits specifically affect scoliosis is nearly nonexistent. We therefore sought to clarify the association between comprehensive sleep behavior patterns and the incidence of this disease.MethodsThis study conducted a prospective cohort study based on the UK Biobank (UKB), including 408,870 participants who did not have scoliosis at baseline. We have constructed a comprehensive sleep scoring system that integrates the following five key indicators: sleep chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. To evaluate the association between healthy sleep patterns and the risk of scoliosis, we conducted a statistical analysis using the Cox proportional hazards regression model.ResultsOver a mean follow-up of 15.82 years, 2,976 incident cases of scoliosis were recorded (0.73%). The 408,870 participants who were free of scoliosis at baseline had a mean age of 56.48 years. Distribution of the healthy sleep score was as follows: 9,939 participants (2.43%) had 0–1 of the five healthy sleep behaviors, 46,175 (11.29%) had 2 behaviors, 115,094 (28.15%) had 3 behaviors, 150,287 (36.76%) had 4 behaviors, and 87,375 (21.37%) had all five. In multivariable models, each 1-point increase in the healthy sleep score was associated with a 10% lower risk of scoliosis [hazard ratio (HR) = 0.90; 95% confidence interval (CI) = 0.87, 0.93]. Compared with the 0–1 score group, the multivariable-adjusted HR (95% CI) for participants with a score of 5 was 0.64 (0.52, 0.80). In subgroup analyses, the inverse association between sleep score and scoliosis risk persisted among participants without diabetes but was absent among those with diabetes (pinteraction < 0.05).ConclusionCohort analysis results confirm that adherence to a healthy sleep-behavior pattern significantly reduces the risk of scoliosis.
Impact of C-reactive protein–triglyceride–glucose and systemic immune-inflammation indices on obstructive sleep apnea in older adults with depression
ObjectiveBoth the C-reactive protein (CRP)–triglyceride–glucose index (CTI) and the systemic immune-inflammation index (SII) are easily accessible, cost-effective, and rapid indices derived from biochemical examinations. The study aimed to identify the roles of the CTI and SII in older adults with comorbid obstructive sleep apnea (OSA) and depression.MethodsThe study included 52 older patients with depression coexisting with OSA and 108 patients with depression but without OSA. The CTI was calculated using the following equation: 0.412 × Ln (CRP) (mg/dL) + Ln [triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The SII was calculated using the formula: platelet × neutrophil/lymphocyte.ResultsA greater proportion of men and a higher mean body mass index were found in older adults with comorbid OSA and depression compared to those with depression only (p < 0.05). Older adults with comorbid OSA and depression also showed higher levels of fasting glucose, triglycerides, CRP, the triglyceride–glucose (TyG) index, and the CTI than those with depression alone. We also found that older adults with comorbid OSA and depression had higher neutrophil counts, a higher neutrophil-to-lymphocyte ratio (NLR), and a higher platelet-to-lymphocyte ratio (PLR), and an increased SII compared to those with depression alone. Logistic regression analysis demonstrated that male sex and higher CTI and SII values were correlated with the presence of OSA in patients with depression.ConclusionThe study demonstrated that higher CTI and SII values may be associated with comorbid OSA and depression in older adults.
Case Report: A literature review of the medical complications arising from etomidate-laced vapes and two case studies of hypokalemia associated with etomidate use
Etomidate, traditionally an anesthetic agent, has recently emerged as a substance of misuse through the adulteration of e-vaporizers. Previous reports have raised concerns of associated adrenal dysfunction. In this case report, we describe two patients with a history of etomidate-laced vaporizer use who were incidentally found to have asymptomatic hypokalemia (serum potassium 2.9 mmol/L and 3.3 mmol/L) during outpatient evaluation. Both patients also presented with diffuse and palmer crease hyperpigmentation, a clinical sign frequently seen in adrenal dysfunction. Unlike previously reported cases presenting with neuromuscular weakness or adrenal crisis, this case report highlights subclinical manifestations of endocrine disruption associated with etomidate use. Early screening of asymptomatic hypokalemia in etomidate misuse is therefore important for clinicians treating this emerging group of patients, as this may facilitate timely investigation and prevention progression to severe adrenal complications.
Sexual functioning in trichotillomania and skin picking disorder
BackgroundThis study examines sexual functioning in adults with trichotillomania and skin picking disorder. To our knowledge, no study has examined sexual functioning in either of these disorders.Methods334 adults (mean age=30.21, SD = 8.23, 83.5% cisgender women, 67.6% sexually active with another person in the past month) were recruited from online Reddit communities. Participants completed surveys assessing demographics, sexual functioning, and current and lifetime pulling and picking severity. Comorbidities and treatment history were assessed via dichotomous variables. Sexual functioning was assessed via the Changes in Sexual Functioning Questionnaire – Short Form (CSFQ-14).Results27.1% (n=85) of the sample met criteria for sexual dysfunction. After controlling for relationship status, participants who rated their picking as currently at its worst had significantly lower scores on the Orgasm/Completion subscale. Sexual dysfunction, the total score, and subscales scores were not significantly associated with any current comorbidities or treatment variables.ConclusionsIt is difficult to compare rate of sexual dysfunction in adults with trichotillomania and skin picking disorder with the rate in the general population given the homogeneity of this study’s sample. However, worse skin picking symptoms appear to be associated with worse sexual functioning, particularly in the orgasm domain. Since severity of comorbidities was not assessed in this study, further research is needed to determine whether comorbid disorders have an effect on sexual functioning in this population.
Moral injury in animal care workers: prevalence, pathways, and phenomenology in a cross-sector sample
IntroductionMoral injury, the psychological harm resulting from events that violate one’s deeply held moral beliefs, has been extensively studied in military and healthcare populations but remains largely unexamined among animal care workers.MethodsThis cross-sectional survey of 291 animal care workers across six sectors (rescue, shelter, animal control, veterinary medicine, volunteer/foster, and other) provides the first empirical prevalence estimate of moral injury in this cross-sector population using a validated syndrome measure.ResultsFindings from the Moral Injury Outcome Scale (MIOS) indicate that 83.5% of participants endorsed at least one morally injurious experience pathway; most common was witnessing (63.9%), followed by being affected by others’ transgressions (38.5%) and direct participation (29.2%). Applying published caseness thresholds, 18.9% of the potentially morally injurious event (pMIE) endorsers met criteria for moral injury as a clinical syndrome and an additional 21.4% for moral distress (subclinical), with blended shame and trust violation presentations characterizing the majority (53.1%) of clinical cases. Patient Health Questionnaire-9 scores exceeded the clinical threshold for moderate depression (M = 10.96, SD = 6.27). One-way analysis of variance revealed significant sector differences in functional impairment, trust violations, and depression, with shelter workers reporting the highest levels across nearly all measures. The MIOS Shame subscale was more strongly associated with both depression (r = .646) and functional impairment (r = .343) than the Trust Violations subscale, which showed no significant relationship with functional impairment (r = .045, p = .456). Endorsement of the direct participation pathway was the only exposure pathway significantly associated with caseness classification, with 31.8% of direct participation endorsers meeting criteria for moral injury compared to 12.0% of non-endorsers (p < .001). A departure from standard MIOS administration presenting impact items to all participants revealed that a small number of pMIE non-endorsers met caseness thresholds despite actively denying exposure, raising questions about the comprehensiveness of current pathway categories.DiscussionThese findings identify moral injury as a prevalent and clinically significant occupational experience among animal care workers, with distinct shame-based and trust violation-based mechanisms in predicting functional decline and clinical severity, respectively. Implications for targeted intervention and organizational reform are discussed.
A connectome-based neural correlate of pediatric ADHD hyperactivity–impulsivity symptoms
BackgroundThis study examined the brain networks related to hyperactivity and impulsivity in children with Attention-Deficit/Hyperactivity Disorder (ADHD) and aimed to develop a resting-state functional connectivity marker that can predict symptom severity.MethodsA total of 44 children with ADHD (31 boys and 13 girls; mean age = 8.45 ± 1.52 years; range = 6–12 years) who met DSM-5 criteria were included. Resting-state fMRI data and clinical symptom scores were collected. Connectome-based predictive modeling (CPM) was used to predict hyperactivity–impulsivity symptoms based on whole-brain functional connectivity matrices. Symptoms were assessed using the SNAP-IV Parent and Teacher Rating Scales and the Conners Comprehensive Behavior Rating Scale. Model performance was tested with leave-one-out cross-validation and permutation testing.ResultsThe CPM model based on interregional functional connectivity successfully predicted hyperactivity–impulsivity symptoms (SNAP-IV parent and teacher ratings: r = 0.48, p = 0.001). The model also generalized well within the same dataset, as the selected functional connections significantly predicted hyperactivity–impulsivity scores on the Conners Parent Rating Scale (r = 0.49, p = 0.0009). Further analysis showed that stronger connectivity between the frontoparietal control network (FPN) and the dorsal attention network (DAN), and weaker connectivity between the FPN and the ventral attention network (VAN) and between the FPN and the somatomotor network (SMN), were related to symptom severity.ConclusionsWhole-brain functional connectivity is associated with hyperactivity–impulsivity symptoms in children with ADHD. The findings highlight the key role of FPN-related networks in these symptoms and provide a neural correlate that, pending further validation, represents a preliminary candidate for a neuroimaging marker.
Early biopsychological changes during masculinizing gender-affirming hormone therapy in AFAB transgender individuals: a 4-month prospective study
ObjectiveTransgender individuals frequently experience elevated levels of psychological distress, including anxiety and trauma-related symptoms. Gender-affirming hormone therapy (GAHT) has been associated with improvements in mental health and quality of life; however, early biopsychological changes occurring during the initial phase of masculinizing hormone therapy remain insufficiently understood. The present exploratory longitudinal study investigated early endocrine and psychological changes in transgender individuals assigned female at birth undergoing masculinizing GAHT.MethodsWe conducted a 4-month prospective observational study involving 30 transgender individuals assigned female at birth initiating masculinizing GAHT. Participants were assessed at baseline (prior to treatment initiation), after 2 months, and after 4 months of therapy. Hormonal parameters (estradiol, testosterone, prolactin) and psychological measures including anxiety (HAM-A), trauma-related symptoms (TSC-40), and quality of life (MANSA) were evaluated. Due to the exploratory character of the study and the relatively small sample size, analyses were performed primarily using non-parametric statistical methods, including repeated-measures analyses.ResultsDuring follow-up, expected endocrine changes were observed, including decreased estradiol levels and increased testosterone concentrations. These changes were accompanied by reductions in anxiety and trauma-related symptoms and by improvements in quality of life measures over time. Repeated-measures analyses demonstrated significant longitudinal improvements in psychological outcomes across follow-up assessments (p < 0.05). Exploratory associations between hormonal and psychological variables appeared more pronounced after 4 months of treatment, particularly for estradiol in relation to anxiety and quality of life. Earlier assessments demonstrated weaker and less consistent associations. Psychological improvements were not directly proportional to the magnitude of hormonal changes alone, suggesting that psychosocial and treatment-related factors may also contribute to early adaptation during GAHT.ConclusionEarly masculinizing GAHT in transgender individuals assigned female at birth was associated with favorable endocrine and psychological changes during the first 4 months of treatment. The findings support a complex and potentially time-dependent relationship between hormonal alterations and psychological adaptation during early transition. Given the exploratory nature and limited sample size of the present study, further longitudinal research with larger cohorts and comparison groups is needed to clarify the underlying biopsychological mechanisms of GAHT.
CAR T cells take on precancers
Nature Medicine, Published online: 17 June 2026; doi:10.1038/s41591-026-04473-9
CAR T cell therapy can induce deep responses but also severe toxicities in patients with smoldering myeloma, an asymptomatic cancer precursor; given the potential risks and benefits, its success depends on careful patient selection.