Psoriasis is a common, chronic, immune-mediated skin disease affecting more than 40 million individuals worldwide. Psoriasis, along with psoriatic arthritis, are part of a broader psoriatic disease spectrum, and present with inflammatory skin and musculoskeletal manifestations driven by shared genetic, environmental, and immunological mechanisms. Skin psoriasis presents with diverse clinical phenotypes, including chronic plaque psoriasis, guttate, palmoplantar, erythrodermic, and pustular forms. Beyond cutaneous manifestations, psoriasis is associated with a substantial psychosocial burden and a wide range of comorbidities, including mental health disorders and cardio-metabolic diseases. Key psoriasis risk factors include genetic polymorphisms (most notably HLA-C*06:02), obesity, and environmental factors such as trauma, infections, and specific medications. Advances in understanding the key role of the IL-23-IL-17 inflammatory axis and related immunogenetic pathways have redefined psoriasis as a complex immune disorder, leading to the development of highly effective targeted biologic and small-molecule therapies that modulate cytokine signalling and intracellular pathways, offering improved disease control across cutaneous and musculoskeletal domains.

Hallucinogens have been prescribed for the treatment of mental illnesses; however, reports on the dependence potential of hallucinogens across species remain inconsistent. Non-human primate (NHP) self-administration model are suitable for evaluating species-specific reinforcement behavior induced by hallucinogens. In this study, we demonstrated that 4-bromo-2,5-dimethoxyphenethylamine (2C-B) was self-administered orally in freely moving marmoset (Callithrix jacchus). 2C-B-treated mice did not demonstrate reinforcement behavior in self-administration paradigm as well as brain stimulation behavior in intracranial self-stimulation (ICSS) test. Interestingly, 2C-B-induced dopamine neuronal activity was demonstrated only in the brain of marmosets as evidenced by fluorescent false neurotransmitter assessment and measurement of synaptosome dopamine levels. We sought to study possible molecular mechanisms underlying this and docking simulations revealed that 2C-B occupied a binding pocket overlapping the canonical dopamine-binding site in both species but adopted a distinct interaction pattern in marmoset DAT involving Leu321. Pull-down assays demonstrated stronger DAT-associated 2C-B binding in marmosets than in mice. Furthermore, 2C-B produced greater inhibition of DAT-mediated FFN102 uptake in cells expressing marmoset or human DAT than in cells expressing mouse DAT, whereas substitution of Leu321 abolished this effect. Collectively, these findings demonstrate that 2C-B induces reward-related behaviors in marmosets and identify species-specific DAT-2C-B interactions as a potential mechanism underlying differential dopaminergic and behavioral responses across species.

The comparative efficacy of acceptance and commitment therapy (ACT) relative to other bona fide psychotherapies has been obscured by methodological limitations and variability in how ACT and active comparators are operationalized. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing full-model ACT (therapist-delivered, multi-session interventions targeting the core ACT processes) to bona fide psychotherapies. We identified 34 RCTs meeting our inclusion criteria. In line with prior critiques of the ACT literature, we identified several common methodological shortcomings, such as lack of preregistration of primary outcomes and hypotheses, inadequate statistical power for detecting differential effects, limited use of intent-to-treat analyses, and interpretive overreach. Random-effects three-level meta-analyses indicated that full-model ACT was not superior to bona fide psychotherapies on mental and behavioral health outcomes (g = -0.01, p = .86). Secondary, hypothesis-generating post hoc analyses examined clinical significance, ACT-targeted processes, and an exploratory TOST comparison against a prespecified equivalence region (g = ±0.20). Current RCT evidence does not justify recommending full-model ACT over other established treatments. Further progress will require more rigorous comparative trials and idiographic designs that better align with the ACT model.

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.