Identifying traits of narcissistic personality disorder (NPD) is clinically challenging, yet early detection can significantly improve outcomes. Online forums have become a major source of self-expression, offering new opportunities to understand mental health. However, analyzing this complex language requires new tools.

This study aims to determine whether a machine learning model could be trained to reliably detect language patterns associated with NPD traits in Reddit posts. Specifically, we sought to identify both authors who exhibit these traits and posts discussing individuals with these traits.

We analyzed 75,985 posts from 4 Reddit communities (r/Narcissism, r/DeepThoughts, r/Showerthoughts, and r/ImposterSyndrome). A subset of 966 posts was annotated by 2 psychiatrists to create a reliable dataset. Using a range of machine learning techniques, from traditional text analysis to modern transformer-based embedding models, we trained the system to distinguish posts containing NPD-trait markers from general reflective posts. This secondary analysis of deidentified public Reddit data was exempted by the Boğaziçi University FMINAREK (Fen Bilimleri ve Mühendislik Alanları İnsan Araştırmaları Etik Kurulu) Institutional Review Board (exemption/application number 2025-13).

Our models demonstrated high accuracy. The modern embedding-based models were particularly effective, achieving a mean F1-score of 0.90, indicating a strong balance between recall and precision by correctly identifying posts with NPD-trait markers while minimizing false positives. The models remained effective even when common keywords such as "narcissism" were removed, with a mean relative F1-score decrease of 3.6% for the frequency-based baseline classifier and less than 2% (1.9% and 0.8%) for the embedding models.

This study demonstrates that automated analysis of online posts is a promising approach for understanding and identifying NPD traits. Although this technology has potential for future clinical applications, it is currently a research tool and should be used only with strict ethical oversight, not for public-facing diagnosis.

We hypothesized that a dynamic surveillance strategy guided by circulating tumor DNA (ctDNA) methylation would increase the rate of curative-intent therapy for recurrence in patients with nonmetastatic colorectal cancer (CRC) after curative resection.

The FIND trial (ClinicalTrials.gov identifier: NCT05904665) is a prospective, multicenter, randomized, phase III study. Patients with nonmetastatic CRC were randomly assigned to ctDNA-guided surveillance or standard computed tomography (CT)-based monitoring. In the ctDNA-guided group, a positive ctDNA result triggered immediate CT imaging; if negative, bimonthly CT continued alongside quarterly ctDNA testing. After two consecutive ctDNA-negative results, imaging reverted to standard frequency. The primary end point was the proportion of patients with recurrence receiving curative-intent metastasis-directed therapy.

Among 584 eligible patients (289 ctDNA-guided, 295 control) in the modified intention-to-treat population, with a median follow-up of 23.3 months, recurrence rates were similar (18.0% v 18.6%, P = .919). The ctDNA-guided group had a significantly higher rate of curative-intent treatment (48.1% v 23.6%, relative risk 2.03, P = .008). The median time to clinical recurrence was significantly shorter in the ctDNA-guided group than in the control group (9.5 v 13.4 months; P < .001), representing a lead time of 3.9 months. Among recurrences confined to the liver and/or lungs, the ctDNA-guided group showed higher curative resection rates (42.3% v 18.2%, P = .002). These patients had more favorable hepatic metastatic features: fewer lesions (≤3: 75.0% v 28.6%, P = .005), smaller tumor size (≤3 cm: 90.0% v 57.1%, P = .033), and more unilobar disease (80.0% v 28.6%, P = .002).

ctDNA methylation-guided dynamic surveillance improves the rate of curative-intent therapy for recurrence in patients with initially nonmetastatic CRC through earlier detection of resectable metastases, pending validation of long-term survival benefit in future analyses with mature data.

Several novel pharmacological therapies for chronic kidney disease (CKD) have been shown to reduce risks of disease progression, cardiovascular events, and mortality. However, their effects on health-related quality of life (HRQoL) remain scattered across trials and are difficult to interpret, owing to variability in instruments used and other design related factors.

PubMed and Web of Science were searched for randomized clinical trials of pharmacological interventions aimed at slowing CKD progression in adults with non-dialysis CKD, published between January 2000 and January 2026. Two authors independently screened and extracted data. Data on study characteristics, HRQoL instruments used, and intervention effects were synthesized descriptively, and key methodological considerations were reviewed.

Of 16,624 screened records, 13 trials collected HRQoL data. HRQoL was measured mainly using the EuroQol 5-Dimension questionnaire (EQ-5D; n=8), the 36-Item Short Form Health Survey (SF-36; n=4), or the Kidney Disease Quality of Life-36 questionnaire (KDQOL-36; n=5). Nine trials reported the effects of interventions on HRQoL. Three demonstrated statistically significant effects in at least one HRQoL domain, all involving interventions that also slowed CKD progression. Effects were generally greater for physical than for mental health domains and were detected more frequently using the disease-specific KDQOL-36, particularly in the symptoms and effects domains, than using the generic EQ-5D. Observed population average intervention effects generally were below conventional minimal clinically important difference thresholds at the population level, though individual-level benefits were evident.

The impact of disease-modifying therapies on HRQoL in non-dialysis CKD is heterogeneous, instrument-dependent, and domain-specific. Consideration of the selected instrument, baseline HRQoL, duration of follow-up, missing data, and potential mediation through clinical events is important when interpreting HRQoL findings. Future trials should incorporate kidney-specific HRQoL instruments and report results for all domains using multiple effect measures.

Prospective multicenter cohort study.

To assess the impact of preoperative inability to walk on surgical outcomes in degenerative cervical myelopathy (DCM) and to identify factors linked to persistent inability to walk.

Inability to walk signifies advanced neurological impairment in DCM and is associated with functional disability. However, its effects on postoperative recovery and prognostic factors remain unclear.

A total of 935 patients with DCM from ten spine centers were analyzed. Preoperative inability to walk was defined as a Japanese Orthopaedic Association (JOA) lower extremity score ≤1. Patients were classified into two groups: those who could walk (n=706) and those who could not walk (n=229). Among those unable to walk preoperatively, outcomes at 2 years were categorized as improved or persistent. Clinical outcomes included the JOA score, visual analog scale, JOACMEQ, SF-36, and NPSI. General linear models were used for adjusted comparisons, and logistic regression was used to identify factors associated with persistent inability to walk.

Patients unable to walk preoperatively had worse baseline status but showed greater absolute improvement in the JOA scores than those able to walk (ΔJOA, 4.3 vs. 2.5, P <0.001). The JOA score recovery rates were similar across the groups. Among patients with preoperative inability to walk, 72.1% regained the ability to walk, whereas 27.9% remained unable to walk at 2 years. Cardiac disease (OR, 2.949), cerebrovascular disease (OR, 5.373), and longer symptom duration (OR, 1.015) were independently associated with a persistent inability to walk. Improvements in mental health and neuropathic pain were not associated with walking recovery.

Most patients with DCM who were unable to walk preoperatively regained their walking ability after surgery. However, vascular comorbidities and longer symptom durations were associated with a persistent inability to walk, which may inform surgical timing and patient counseling.

II.

Transdiagnostic group interventions targeting emotion regulation (ER) are commonly offered to individuals with severe mental illness (SMI). Previous feasibility studies have provided insufficient information to support progression to effectiveness evaluation of scaled-up delivery. We aimed to address this gap.

We conducted a feasibility randomised controlled trial of a protocolised group ER intervention for individuals with SMI, delivered online and facilitated by a trained junior workforce. Feasibility markers were recruitment, retention, data completeness, intervention uptake and completion (≥50% sessions), adherence to the intervention protocol, and participant satisfaction. Participants were recruited from community mental health services and randomly allocated (1:1) to intervention or waitlist control groups.

Feasibility was demonstrated, with 6/7 markers categorised 'green' and 1/7 'amber' against predetermined progression criteria. Recruitment targets were met (n = 34 service users; n = 9 junior facilitators), retention was 85.3%, and paired outcome completion was 82.4%. Staff self-reported high adherence and participant satisfaction was 89.6%. Intervention completion was 61.1% (green target=>80%; amber target=>60%), suggesting scope to improve engagement.

Participants dropping out of the intervention were lost to follow-up, limiting assessment of reasons for non-continuation. Implications of unblinded researchers at post-assessment are discussed. Group-level and contextual treatment data were not routinely collected due to naturalistic intervention delivery.

An effectiveness trial of a protocolised group ER intervention for SMI, delivered online by junior staff, is feasible. A larger multi-site pilot trial to estimate sample size for a confirmatory trial, incorporating methodological refinements to increase intervention completion, is the next step.

This study evaluated the effectiveness of school-based psychosocial interventions for conflict-affected adolescents in the Middle Eastern countries.

We searched PubMed, Scopus, and Web of Science from inception to August 2025 for studies evaluating school-based interventions targeting mental health outcomes in refugee adolescents in Middle East. Eligible studies included randomized controlled trials, cohort studies, and pre-post intervention designs. Random-effects meta-analyses were conducted for single-arm (pre-post) and double-arm (intervention versus control) comparisons, using R programming for statistical analysis.

Nine studies involving predominantly Syrian, Palestinian, and Afghan refugee adolescents met the inclusion criteria. Single-arm analyses demonstrated significant reductions in post-traumatic stress disorder (PTSD) symptoms [mean raw score change (MRAW) = -7.50, 95% confidence interval (CI): -10.53 to -4.46], anxiety (MRAW = -9.33, 95% CI: -16.43 to -2.23), and emotional-behavioral difficulties (MRAW = -2.21, 95% CI: -3.20 to -1.22). Double-arm analyses showed significant effects for PTSD/stress [standardized mean difference (SMD) = -0.63, 95% CI: -1.26 to -0.001] and emotional-behavioral difficulties (SMD = -3.47, 95% CI: -6.55 to -0.40), but not for depression or anxiety when compared with controls.

School-based psychosocial interventions demonstrate effectiveness in reducing trauma-related symptoms and improving emotional regulation among conflict-affected adolescents in Middle Eastern contexts, although substantial heterogeneity warrants cautious interpretation. While findings support their potential integration into humanitarian education programming, conclusions should be considered in light of variability in study design and populations.

A fundamental but unanswered question in neuropsychiatry is whether the psychiatric symptoms of epilepsy are caused by the same or a separate pathophysiology as seizures. To address this question, we investigated a monogenic form of epilepsy (pyridoxine-dependent epilepsy) caused by aldehyde dehydrogenase 7 family member A1 (ALDH7A1) mutations. ALDH7A1 global knockout mice exhibited both seizure-associated and maladaptive affective behavioral phenotypes. However, seizure phenotypes were caused by ALDH7A1 deletion in hepatocytes whereas maladaptive affective behaviors were caused by ALDH7A1 deletion in astrocytes. Deletion in astrocytes disrupted astrocyte redox homeostasis, impairing regulation of extracellular ion concentrations and reducing neuronal activity in the prelimbic cortex. Sulforaphane, which activates the NRF2 antioxidant pathway, restored prelimbic neuronal activity and rescued maladaptive affective behaviors in ALDH7A1 knockout mice but did not prevent seizures. These studies implicate astrocyte redox homeostasis and prelimbic hypoactivity in maladaptive affective behavioral phenotypes in a congenital form of epilepsy, which are mechanistically and therapeutically dissociable from seizure pathophysiology.

Vascular endothelial growth factor A (VEGFA) plays a critical role in the pathogenesis of diabetic macular edema (DME) in patients with type 2 diabetes mellitus (T2DM). Herein, we sought to determine whether palmitoylation modulates the stability and function of VEGFA in the context of DME.

VEGFA protein levels were measured by western blotting in retinal pigment epithelial (RPE) tissues from mice and in cultured RPE cell lines. Palmitoylation of VEGFA was assessed using acyl‑biotin exchange (ABE) and Click‑iT pulldown assays. Cell proliferation was evaluated with the Cell Counting Kit‑8 (CCK‑8) assay. The interaction between VEGFA and zinc finger DHHC-type containing 19 (ZDHHC19) was examined by co‑immunoprecipitation. Retinal histopathology in DME mice was evaluated by hematoxylin‑eosin (H&E) staining.

VEGFA levels were elevated in the RPE of DME mice compared with those of T2DM mice. Pharmacological inhibition of palmitoylation with 2‑bromopalmitate (2‑BP) reduced VEGFA protein expression in cultured cells. ZDHHC19 was identified as the palmitoyltransferase responsible for VEGFA. Wild‑type ZDHHC19 failed to palmitoylate the VEGFA‑C387A mutant, and the catalytically inactive ZDHHC19‑C142S mutant also lacked activity toward VEGFA. Overexpression of wild‑type VEGFA or ZDHHC19 significantly promoted RPE cell proliferation, whereas the VEGFA‑C387A and ZDHHC19‑C142S mutants had no effect. Consistent with these in vitro findings, wild‑type VEGFA or ZDHHC19 overexpression exacerbated DME development in mice, while the corresponding mutants did not significantly affect disease progression.

ZDHHC19‑mediated palmitoylation of VEGFA contributes to DME pathogenesis and may serve as a potential therapeutic target and biomarker for this disease.

The online version contains supplementary material available at 10.1007/s40200-026-02023-1.

Antibodies to Epstein-Barr virus (EBV) proteins can predict nasopharyngeal carcinoma (NPC) risk. We previously defined a prototype EBNA1 protein panel and multiplex immunoblot assay that distinguishes NPC risk several years pre-diagnosis. Assay throughput and specificity are critical to effectively implement a population-level screening program. Here, we developed a strip test assay-EBNA1 SeroStrip-HT-with an objective to increase throughput and maximize specificity. EBNA1 full-length (FL) and glycine-alanine repeat deletion mutants (dGAr) were purified from insect and mammalian cells to screen serum IgA/IgG from prospective cohorts in Singapore and Shanghai, China, with known time intervals to NPC diagnosis. Twenty pre-diagnostic sera within 4 years to diagnosis were compared to 96 healthy controls using a nested case-control study design. IgA to mammalian-derived EBNA1 dGAr achieved 85.0% sensitivity and 94.8% specificity (AUC, 0.939) for NPC status. IgA to insect-derived EBNA1 dGAr showed the same sensitivity (85.0%) and similar specificity (93.8%) (AUC, 0.941). IgA to insect-derived EBNA1 FL had a higher 90% sensitivity, but lower 91.7% specificity (AUC, 0.940). Combining EBNA1 FL and dGAr results showed that subjects positive for both proteins had a 243.67 odds ratio for NPC incidence compared to double-negative scores. This study demonstrated the efficacy of EBNA1 SeroStrip-HT for NPC risk assessment and stratification in high- and intermediate-risk populations, yielding high accuracy and a 12-fold increased throughput over the prototype. The insect system was appropriate for large-scale production of purified EBNA1. Larger, geographically diverse cohorts are warranted to confirm these results, especially in low-incidence populations.

The mechanisms underlying pharmacological treatments for stimulant use disorders are poorly understood. This study examined whether changes in craving, depressive symptoms, and/or impulsivity mediate treatment effect in pharmacotherapy with combined naltrexone and bupropion for methamphetamine use disorder (MUD).

The study was based on secondary analysis of data from the Accelerated Development of Additive Pharmacotherapy Treatment for methamphetamine disorder (ADAPT-2) trial which randomized adults with MUD to combined treatment with injectable naltrexone (380 mg every 3 weeks) plus oral bupropion (450 mg daily) versus placebo. A total of 403 adults with MUD participated in the first stage; 225 of first stage participants in the placebo arm who did not respond to treatment were re-randomized in the second stage. Mediation effects were examined using longitudinal multi-level structural equation modeling.

Naltrexone-bupropion treatment was associated with decreases in drug use, craving, depressive symptoms, and impulsivity. The indirect effect of treatment through change in craving was significant (self-reported use = -0.21, 95% credible interval (CrI) = -0.35, -0.09; drug screen-ascertained use = -0.36, 95% CrI = -0.63, -0.16). Change in craving mediated 56% of the treatment effect on self-reported drug use and 45% of the effect on drug screen-ascertained use. Estimates for mediated effects for depressive symptoms and impulsivity were smaller in magnitude and nonsignificant.

Reduction in craving mediates the effect of naltrexone-bupropion pharmacotherapy in MUD. Craving may serve as a surrogate measure of treatment efficacy in short-term trials and help identify promising candidate medications to be tested in larger and longer-term trials.

ClinicalTrials.gov number: NCT03078075.