BackgroundGastrointestinal adverse events (GI AEs) are the main dose-limiting side effects of metformin in type 2 diabetes mellitus (T2DM), reducing adherence and compromising long-term glycaemic control. Current strategies (dose adjustment or combination therapy) seldom address both tolerability and sustained metabolic efficacy. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that may modulate gut–brain–metabolic pathways—vagal reflexes, inflammation, intestinal barrier function, and enteroendocrine signaling—and thus improve drug tolerance while preserving glycaemic control.MethodsThis single-center, randomized, sham-controlled pilot trial will enroll 60 T2DM patients with metformin-associated GI AEs, randomized 1:1 to either the taVNS group or the sham control group. The intervention lasts 2 weeks with a follow-up at week 4. Assessments at baseline and follow-up include a validated Metformin Symptom Severity Score (total score 0–50; primary outcome), Bristol Stool Form Scale, bowel urgency, glycaemic/metabolic indices [fasting blood glucose (FBG), 2-h postprandial glucose (PG2h), glycated albumin (GA), fasting C-peptide, fasting insulin, HOMA-IR, ISI], and mechanistic biomarkers (GLP-1, 5-HT, IL-6, IL-10, TNF-α, D-lactate, DAO, bile acids). Safety monitoring includes routine hematology, liver and renal function tests.DiscussionBy combining clinical outcomes with targeted biomarker analyses in a randomized design, this pilot study will assess whether taVNS alleviates metformin-associated GI intolerance without impairing glycaemic efficacy, and will provide feasibility data, effect-size estimates, and biomarker selection for future confirmatory trials.Clinical trial registrationTrial registration International Traditional Medicine Clinical Trial Registry (ITMCTR) http://itmctr.ccebtcm.org.cn/, Identifier: ITMCTR2025001086.
The patterns of relapse and abstinence: using machine learning to identify a multidimensional signature of long-term outcome after inpatient alcohol withdrawal treatment
AimsA machine learning approach to identify a multidimensional signature associated with relapse and long-term outcome in alcohol dependence treatment.DesignIn this observational naturalistic study, inpatients with alcohol dependence received qualified detoxification plus CBT (Cognitive Behavioral Therapy) and were followed up 6-months after discharge to assess abstinence and drinking behavior. Cross-validated multivariate sparse partial least squares analysis (SPLS) was used to investigate the relationship between clinical features and four long-term outcome variables.SettingGermany.Participants152 patients (on average 47.8 years old, 72% male) with alcohol dependence, who received inpatient qualified detoxification plus CBT.Measurements35 clinical features were used to cover all three phases of inpatient treatment (pre-, within-, post-treatment). Among these, sociodemographic characteristics, ICD-10 psychiatric diagnoses, previous detoxification treatments, and somatic measurements as well as inpatient treatment setting such as withdrawal medication, liver ultrasound, further information about the patients´ stay, and post-inpatient care were assessed. The four outcome dimensions included: continuous abstinence, abstinence at follow up, daily alcohol consumption, and days of abstinence after discharge.FindingsSix months after withdrawal treatment 46% of the patients achieved continuous abstinence. Socioeconomic, clinical and somatic features across the treatment timeline were analyzed and summarized into a multivariate signature associated with long-term treatment outcome. Thereby, the SPLS algorithm identified regular completion of withdrawal treatment, higher education, and employment status to be most strongly associated with a positive outcome. Alcohol-related hepatic and hematopoietic damage, number of previous withdrawal treatments and living in a shelter were most profoundly associated with a negative outcome.ConclusionConceiving treatment outcome as a multidimensional signature and moving beyond simple binary classifications of relapse versus abstinence may improve the understanding of relapse pathways and support more individualized treatment strategies.
Interoceptive dysfunction and its neural correlates in schizophrenia: protocol for a cross-sectional multimodal MRI study
BackgroundInteroception—the perception and integration of internal bodily signals—is fundamental to emotion regulation, bodily self-awareness, and predictive coding. Emerging evidence suggests that interoceptive disturbances may contribute to core psychopathological features of schizophrenia. Our research group recently conducted a systematic review and meta-analysis demonstrating significant impairments in interoceptive accuracy and sensitivity among individuals with schizophrenia. However, the neural mechanisms underlying these deficits remain unclear.MethodsThis cross-sectional protocol will recruit 30 individuals with schizophrenia and 30 age- and sex-matched healthy controls. Participants will complete (1) behavioral interoceptive assessment using the heartbeat counting task; (2) subjective interoceptive questionnaires, including the Multidimensional Assessment of Interoceptive Awareness (MAIA) and the Body Perception Questionnaire (BPQ); (3) clinical symptom ratings (PANSS, HAM-A, HAM-D); and (4) cognitive testing (TMT, animal fluency, DSST). All participants will undergo multimodal MRI scanning, including structural T1-weighted imaging, resting-state fMRI, and diffusion tensor imaging. Neuroimaging data will be preprocessed and analyzed using DPABISurf, SPM12, and GRETNA. Expected Results: We anticipate that individuals with schizophrenia will show reduced interoceptive accuracy, altered subjective interoceptive awareness, and abnormal intrinsic neural activity and connectivity within interoception-related circuits, including the anterior insula, anterior cingulate cortex, amygdala, and thalamus. Structural abnormalities within thalamo-cortical pathways are also expected. Interoceptive deficits are hypothesized to correlate with symptom severity and cognitive performance.ConclusionsThis study will provide an integrated characterization of interoceptive dysfunction and its neural correlates in schizophrenia. Findings may advance understanding of bodily self-disturbance and emotional dysregulation and support the development of future interoception-focused therapeutic approaches.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2500110551.
Anxiety among Chinese primary school teachers under the “double reduction” policy: prevalence and associated factors
ObjectivesThe implementation of the “Double Reduction” Policy in China has raised concerns about increased anxiety levels among primary school teachers. However, the prevalence of anxiety symptoms and the factors associated with them remain unclear. This study aims to investigate the prevalence and correlates of anxiety among primary school teachers under this policy.MethodsA cross-sectional survey was conducted from September to October 2022 among primary school teachers in 15 cities across China. Participants completed a series of questionnaires administered via WeChat to assess anxiety symptoms and potential related factors, including perceived stress, sociodemographic characteristics, and job-related variables. Anxiety and perceived stress were measured using the Generalized Anxiety Disorder-7 (GAD-7) and 10-item Perceived Stress Scale (PSS-10), respectively.ResultsOverall, 44.5% (1,423/3,199) of teachers reported at least mild anxiety symptoms. Among them, 56.43%, 25.30% and 18.27% had mild, moderate, and severe anxiety, respectively. In the final logistic regression model, five variables remained independently associated with anxiety: education level (master’s degree or above: OR = 2.781, 95% CI: 1.858–4.163), income dissatisfaction (OR = 1.487, 95% CI: 1.205–1.834), intermediate professional title (OR = 1.372, 95% CI: 1.084–1.738), younger age (OR = 0.979, 95% CI: 0.966–0.993), and perceived stress (OR = 1.489, 95% CI: 1.443–1.538).ConclusionAnxiety was prevalent among primary school teachers during the implementation of the “Double Reduction” Policy. Higher education level, income dissatisfaction, intermediate professional title, younger age, and elevated perceived stress were significant risk factors for anxiety. Therefore, interventions focusing on stress management and occupational support may help improve teachers’ mental well-being.
Psychometric validation of the revised Chinese version of the Dimensional Anhedonia Rating Scale in psychiatric outpatients
ObjectiveTo refine the Chinese version of the Dimensional Anhedonia Rating Scale (DARS) and evaluate the psychometric properties of the Revised Chinese DARS (RC-DARS) in a large sample of first-visit psychiatric outpatients.MethodsThe study was conducted in two sequential phases at a specialized psychiatric hospital. In Phase I (n = 277), the existing Chinese DARS underwent semantic and cultural refinement in accordance with ISPOR and TRAPD guidelines, incorporating cognitive interviews and back-translation procedures. In Phase II (n = 788), the RC-DARS was administered alongside the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Index (PSQI), and the MMPI Suicide Ideation Subscale (MMPI-SI). Exploratory and confirmatory factor analyses were conducted using common-factor extraction and the WLSMV estimator for ordinal indicators. Internal consistency, gender-based measurement invariance, and convergent validity were evaluated.ResultsExploratory analyses supported a four-factor domain structure. Confirmatory factor analysis demonstrated good model fit for the domain-based model (χ²/df = 3.81, CFI = 0.98, TLI = 0.97, RMSEA = 0.08, SRMR = 0.05), with substantially superior fit relative to an alternative reward-processing model. Internal consistency was excellent (Cronbach’s α = 0.95; McDonald’s ω = 0.96). Multi-group analyses supported configural, metric, and scalar invariance across gender (ΔCFI < 0.01). RC-DARS total scores were significantly negatively correlated with depressive symptoms (r = −0.443), anxiety (r = −0.317), sleep disturbance (r = −0.494), and suicide risk (r = −0.312) (all p <.001). Individuals with severe depressive symptoms exhibited significantly lower RC-DARS scores than those below the clinical threshold.ConclusionsThe RC-DARS demonstrates robust psychometric properties in a first-visit outpatient sample. The revision primarily enhances semantic precision and structural differentiation without materially altering score distributions. The scale may serve as a refined instrument for dimensional assessment of anhedonia in similar clinical contexts, pending longitudinal and multi-site validation.
Two faces of police stress: Spanish validation of operational and organizational PSQ scales
IntroductionPolice officers face multiple psychosocial risks stemming from operational and organizational aspects of their work. The Police Stress Questionnaire (PSQ) includes operational (PSQ-Op) and organizational (PSQ-Org) versions to assess these stressors. This study aimed to validate both versions in a sample of Mossos d’Esquadra, examining their factorial structure, reliability, and convergent and discriminant validity.MethodsExploratory and confirmatory factor analyses were conducted to examine the internal structure of the PSQ-Op and PSQ-Org. Internal consistency was evaluated using reliability indices. Convergent and discriminant validity were assessed through correlations with measures of anxiety, depression, and coping strategies.ResultsBoth PSQ-Op and PSQ-Org showed an essentially unidimensional structure, indicating that each scale measures a coherent latent construct. Operational and organizational stress remained distinct domains. Both scales exhibited high reliability and adequate psychometric properties. Subtle gender differences were noted in the perception of specific stressors.DiscussionThese findings support the validity and reliability of the PSQ-Op and PSQ-Org for assessing psychosocial risks among Spanish police officers. The scales can inform interventions targeting workplace stress prevention and the promotion of organizational well-being, emphasizing the need to address operational and organizational stressors separately.
Synthetic microbial co-cultures for modular bioelectronic sensing in diverse environments
Nature Biotechnology, Published online: 17 April 2026; doi:10.1038/s41587-026-03075-7
Modular integration of bacterial strains expands the application range of whole-cell bioelectric sensors.
New gene-editing approaches for β-hemoglobinopathies
Nature Medicine, Published online: 17 April 2026; doi:10.1038/d41591-026-00021-7
Three phase 1/2 trials show that direct editing of HBG1 and HBG2 promoters is a promising disease‑agnostic strategy for treating β‑hemoglobinopathies such as sickle-cell disease and β-thalassemia.
A roadmap to competitive preclinical packages
Nature Medicine, Published online: 17 April 2026; doi:10.1038/s41591-026-04345-2
Should researchers avoid translational research in animals in favor of human or AI models? We argue that this debate should focus not on comparing species but instead on how experimental systems can be combined to maximize mechanistic confidence, human relevance, and real-world decision-making value.
Microstructure makes ePTFE a versatile medtech material
By Matt Navarro, Aptyx Expanded polytetrafluoroethylene (ePTFE) has become a staple in the medical device industry for applications ranging from vascular grafts to stent encapsulations and more. It’s known for chemical inertness, biocompatibility, flexibility, and durability. What may surprise engineers is that ePTFE is not a single, uniform material. It takes several forms with varying…
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