Sexual orientation concealment is a prevalent minority stressor among LGBTQ+ people (including nonbinary people) and it is associated with a series of adverse mental health outcomes. The Sexual Orientation Concealment Scale (SOCS) is a widely used brief measure assessing sexual orientation concealment. Although the SOCS has been used with diverse cisgender populations, its validity for nonbinary people, including those of varied racial/ethnic backgrounds and sexual orientations, remains unknown. Based on data from an international sample of 340 nonbinary LGBTQ+ individuals, the present study reports the findings of a confirmatory factor analysis to assess the one-factor structure and validity of the SOCS, as well as measurement invariance by racial/ethnic identity (i.e. white and Black, Indigenous, and People of Colour [BIPOC]) and sexual orientation (i.e. monosexual, bi+, and queer). The model fit the data well for the one-factor solution, and we observed partial scalar invariance by racial/ethnic identity and sexual orientation. These findings indicate that the SOCS is valid for use with nonbinary people and provide preliminary support for its use across racial/ethnic and sexual orientation groups. We outline implications for future investigation to increase the cohesion of this body of work, and for clinical practice with nonbinary people.

BRD4, a member of the bromodomain and extra-terminal (BET) family of epigenetic readers, plays a central role in transcriptional regulation and is implicated in a wide spectrum of diseases. Although BRD4 inhibitors targeting both bromodomains have advanced into clinical studies, their development and therapeutic use are limited by dose-limiting toxicities associated with nonselective BET inhibition. These limitations underscore the need for domain-selective targeting strategies. In this study, we performed fragment-based screening of a 200-compound diversity library against BRD4-BD2, identifying three chemically distinct hits: CCBT-T-226 (methyl 2-(2-(3,5-dimethylisoxazol-4-yl)-acetamido)-5-propylthiazole-4-carboxylate), CCBT-F-70 (2-(benzylamino)-pyrimidin-4-(3H)-one), and CCBT-F-182 (3-(8-methyl-3,8a-dihydroimidazo-[1,2-a]-pyridin-2-yl)-aniline). These fragments were validated as binders using TSA, ITC, STD-NMR, and ¹H-¹⁵N HSQC NMR. Among them, CCBT-T-226 and CCBT-F-182 exhibited measurable BD2-over-BD1 selectivity, with CCBT-F-182 showing a pronounced domain preference, and CCBT-T-226 demonstrating approximately 7-fold selectivity for BD2 over BD1. X-ray crystallography of the BRD4-BD2-CCBT-F-70 complex, together with cofolding models for CCBT-T-226 and CCBT-F-182, provides a structural framework for the rational, structure-guided development of potent and selective BRD4-BD2 inhibitors.

General-purpose large language models are increasingly used by patients and caregivers to obtain mental health information and guidance about when professional care is required. In late-life depression, broadly accurate information may nevertheless be unsafe when cognitive change, multimorbidity, frailty, polypharmacy, self-neglect, caregiver dependence, or suicide risk is not adequately recognized. This study compared the clinical accuracy, safety, geriatric-specific appropriateness, triage performance, and response consistency of three large language models when answering patient- and caregiver-centered questions about late-life depression.

We conducted a blinded, paired benchmarking study using 90 questions covering six geriatric psychiatry domains and equally distributed across low-, moderate-, and high-risk strata. Each question was submitted independently to GPT-5.5 Instant via ChatGPT, Gemini 3.5 Flash via Gemini, and Seed2.0 Pro via Doubao, generating 270 primary-round responses. A stratified subset of 30 questions was resubmitted in separate conversations to assess test-retest consistency, yielding 360 responses overall. Two psychiatrists independently evaluated anonymized outputs against prespecified item-specific reference standards, with clinically important disagreements adjudicated by a third senior psychiatrist. The primary outcome was the proportion of clinically acceptable responses, defined using accuracy, clinical safety, geriatric appropriateness, warning-sign recognition, and triage criteria.

Clinically acceptable responses were generated for 78.9% of questions by ChatGPT, 72.2% by Gemini, and 60.0% by Doubao (overall P<0.001). The difference between ChatGPT and Gemini was not statistically significant, whereas both outperformed Doubao. This model ranking remained unchanged under alternative core-safety and more stringent optimal-response definitions. Complete geriatric-specific appropriateness was achieved in 64.4%, 55.6%, and 43.3% of responses, respectively. Major safety errors occurred in 5.6% of ChatGPT responses, 10.0% of Gemini responses, and 16.7% of Doubao responses (raw P = 0.015; FDR-adjusted q=0.023). Performance declined substantially with increasing clinical risk. In exploratory post hoc caregiver-centered analyses, clinical acceptability was 76.7% for ChatGPT, 70.0% for Gemini, and 53.3% for Doubao, while explicit caregiver-directed action was present in 80.0%, 70.0%, and 53.3% of responses, respectively. Among high-risk questions, clinically acceptable response rates were 63.3%, 50.0%, and 36.7%, while under-triage occurred in 16.7%, 26.7%, and 36.7% of responses, respectively. Test-retest clinical consistency was highest for ChatGPT (90.0%), followed by Gemini (83.3%) and Doubao (73.3%).

The three models answered many late-life depression questions accurately and safely, but none demonstrated consistently reliable performance across complex or high-risk scenarios. Clinically important weaknesses involved geriatric-specific interpretation, recognition of indirect risk signals, crisis-response completeness, under-triage, and response stability. General-purpose large language models may support selected low-risk educational tasks but should not independently guide emergency triage, medication changes, suicide-risk management, or other safety-critical decisions in older adults.

Real-world evidence for lecanemab remains limited, particularly among Asian populations. We evaluated the feasibility, safety, biomarker profiles, and short-term clinical outcomes of lecanemab in practice in Japan.

We screened 321 patients with early Alzheimer's disease (AD) and confirmed amyloid pathology using amyloid positron emission tomography (PET) or cerebrospinal fluid analysis. Plasma amyloid-β42/40 was assessed when available. Among these, 102 initiated lecanemab and underwent structured magnetic resonance imaging (MRI) surveillance with 6 months of follow-up.

Most treated patients had a Clinical Dementia Rating-Global (CDR-Global) score of 0.5 (96.1%), and 6-month treatment persistence exceeded 85%. Amyloid-related imaging abnormalities (ARIA), predominantly mild and asymptomatic ARIA-H, occurred in 11.4%, whereas no cases of isolated ARIA with effusion or edema (ARIA-E) were observed. One macrohemorrhagic and two moderate-severe radiographic ARIA with hemorrhage or hemosiderin deposition (ARIA-H) developed, which led to discontinuation of the treatment. Cognitive and functional measures remained generally stable over 6 months, with changes comparable to those reported in the phase 3 CLARITY-AD trial. Plasma-PET discordance highlighted the complementary value of multimodal biomarker interpretation.

Lecanemab was feasible and generally well tolerated under structured MRI monitoring in routine Japanese practice.

Kratom has experienced rapidly rising popularity in Western countries, particularly the United States where an estimated 10-20 million individuals use it for management of mental health conditions, performance enhancement, substance use substitution, and chronic pain conditions. Despite widespread anecdotal claims of analgesic benefits, robust preclinical data on kratom's efficacy remain limited, necessitating translational models to evaluate its potential. The objective of this study was to evaluate the analgesic efficacy of an encapsulated kratom extract compared to buprenorphine and placebo in healthy beagle dogs using quantitative sensory testing.

Eight healthy female spayed beagle dogs were included in this blinded, randomized, three-phase, crossover design following IACUC approval. Each dog received the following three interventions across the study period: encapsulated kratom extract by mouth at a 1 mg/kg target oral mitragynine dose, an oral placebo, or buprenorphine 0.02 mg/kg intramuscular. Each dog underwent baseline quantitative sensory testing and then at 0.5, 2, 4, 6, and 8 h post-dosing. Three doses of kratom and placebo were administered prior to sensory testing. Sedation scores were also obtained at each time point. Quantitative sensory testing outcomes were analyzed separately by modality using trimmed replicate means, with changes from baseline calculated for each dog and time point. Modality-specific minimum detectable change thresholds, derived from baseline within-time point variability, were used to classify meaningful responses. Treatment effects were evaluated using linear mixed-effects models (treatment, time, and sedation score as fixed effects; dog as a random effect), supplemented by summaries of peak change, time to peak, responder proportions, and trapezoidal area under the curve for both threshold changes and meaningful response burden.

Across QST modalities, buprenorphine elicited the largest threshold increases, with group-average peaks exceeding modality-specific MDC ₉₅ thresholds and high individual-dog responder rates (≥87.5%) in electrical, mechanical, and thermal tests; kratom produced modality-dependent effects, strongest in electrical QST (87.5% responders) and modest in thermal and mechanical.

These findings underscore the complex pharmacological profile of kratom, suggesting differential modulation of nociceptive pathways that warrants further investigation into its multiple alkaloids, active metabolites, and their specific contributions to the observed analgesic effect.

Cybervictimization and cyberaggression are increasingly recognized as public health concerns among university students; however, evidence from Thailand remains limited.

This study examined whether cybervictimization was associated with cyberaggression endorsement and whether self-esteem moderated this association. We used a two-part zero-inflated Poisson (ZIP) framework to distinguish between (a) a structural-zero/no-endorsement process and (b) the extent of cyberaggression endorsement among individuals at risk.

A cross-sectional online survey was conducted in January 2023 among university students in Chiang Mai, Thailand (N = 414). Cybervictimization was assessed using the victimization subscale of the Thai version of the Cyberaggression-Perpetration and Victimization Scale. Cyberaggression was operationalized as a bounded behavioral endorsement count (AGGRESSO; range = 0-5), reflecting the number of cyberaggressive perpetration behaviors endorsed during the past month. Self-esteem was assessed using the Thai Rosenberg Self-Esteem Scale. Competing Poisson, negative binomial, and ZIP models were compared using information criteria.

Model comparisons supported the ZIP specification (AIC = 484.143; BIC = 516.350). In the ZIP count component, higher self-esteem was associated with a lower extent of cyberaggression endorsement among at-risk individuals (b = -0.078, p = 0.005). Cybervictimization (b = 0.048, p = 0.386) and the cybervictimization × self-esteem interaction (b = 0.015, p = 0.180) were not statistically significant in this component.In the zero-inflation component, the cybervictimization × self-esteem interaction was statistically significant (b = -0.106, p = 0.050), while the main effect of cybervictimization was marginal (b = -1.406, p = 0.054). These findings indicate that the association between cybervictimization and structural non-endorsement-equivalently, the likelihood of any cyberaggression endorsement-differed according to self-esteem. Sensitivity analyses using binary and ordinal outcome specifications produced a consistent pattern: cybervictimization and its interaction with self-esteem were most evident for the involvement aspect of cyberaggression (i.e., any endorsement), rather than the extent of endorsement.

Cybervictimization was more strongly related to cyberaggression involvement than to the extent of cyberaggression endorsement among at-risk individuals, whereas self-esteem showed a component-specific pattern. These findings demonstrate the value of distinguishing between involvement and endorsement extent in cyberaggression research. University prevention efforts may benefit from timely support following cybervictimization, together with interventions that strengthen self-regulation and adaptive coping resources.

Personality traits represent consistent patterns of expressions in an individual's cognition, behaviour and emotion and are therefore relevant to psychopathology and present markers for psychological vulnerability. The S-REF model has implications for personality and trait theory because it describes higher-order cognitions involved in self-regulation, persistence and the stability of cognitive-behavioural patterns. Variability in features of the S-REF should be associated with personality dimensions and most strongly associated with those reflecting stable psychological vulnerability. Individual differences in metacognitive knowledge representing beliefs about the personal uncontrollability and dangerousness of thoughts is a central variable in the S-REF. The present study aimed to test the hypothesis that such negative metacognitions are associated with personality factors, with the most robust relationships predicted to be with personality dimensions representing psychological vulnerability (e.g., neuroticism). However, we also predicted wider (but weaker) associations between the MCQ factor and a range of personality dimensions because negative metacognitive beliefs in the S-REF model influence the stability of broader cognition-behaviour patterns.

We tested relationships among 296 individuals who completed the full NEO-PI-R. Using a network approach, the structure of partial correlations between negative metacognitions and Big Five personality traits were visualized and explored with an exploratory directed acyclic graph (DAG) of the conditional-dependence structure among these variables.

Negative metacognitions showed the highest expected influence in the network. The conditional-independence pattern was more consistent with negative metacognitive beliefs preceding neuroticism than the reverse, but this ordering should not be interpreted as evidence of a causal relationship due to the cross-sectional design.

The results are consistent with predictions based on the S-REF model, that negative metacognitive beliefs are associated with, and structurally central among personality dimensions linked to psychological vulnerability. The directional findings are offered as an exploratory hypothesis for future longitudinal or experimental testing rather than as established causal or mechanistic relationships.

The study aimed to estimate energy, macro, and micronutrient intakes and to compute the probability of adequacy (PA) of 11 selected micronutrient intakes by age, sex, and vulnerabilities.

This study analyzed dietary data from two nationally representative surveys in Bangladesh: the BIHS 2015 (N = 13,086; rural only) and the NSB 2017-2018 (N = 3,116; rural and urban, all divisions). Participants included individuals of all ages and both sexes. Primary outcomes were energy intake and micronutrient adequacy, estimated using usual intake and mean probability of adequacy (MPA) for 11 micronutrients. Secondary outcomes included intake of 13 food groups, macronutrients, dietary fiber, and food-group contributions to nutrient intake, standardized to the individual level using adult male equivalents.

The study showed that cereals dominated diets, with low intake of fruits, leafy vegetables, pulses, milk, and nuts. Nutrient adequacy was low for calcium, riboflavin, vitamin B12, folate, zinc, and vitamin A, except for niacin and vitamin B6. The median MPA across 11 micronutrients was low for all age and physiological groups. Females had lower odds (AOR: 0.58, 95% CI: 0.49, 0.70, p < 0.001) of having higher MPA than males. Adolescents (10-18 years) were less likely (AOR: 0.57, 95% CI: 0.37, 0.88, P = 0.01) to have higher MPA compared to children (1-5 years). Participants from large families (>4 members) had lower odds (AOR: 0.70, 95% CI: 0.57, 0.86, p = 0.001) of having higher MPA than those from smaller families. Children under 2 years were less likely (AOR: 0.51, 95% CI: 0.41, 0.64, p < 0.001) to have higher MPA than women of reproductive age (WRA).

The study found cereal-dominated diets with low consumption of fruits, leafy vegetables, pulses, milk, and nuts, potentially contributing to widespread inadequacy of essential micronutrients across all age groups. Policies and strategies should promote the production, affordability, accessibility, and consumption of nutrient-dense foods, particularly pulses, fruits, nuts and seeds, leafy vegetables, and dairy products, to improve micronutrient adequacy.

Intravenous thrombolysis (IVT) before interhospital transfer for endovascular thrombectomy (EVT) in patients with large-vessel occlusion acute ischemic stroke (LVO-AIS) remains controversial. We aimed to evaluate the efficacy and safety of pre-transfer IVT in LVO-AIS patients who presented to primary stroke centers (PSCs) and required transfer to comprehensive stroke centers (CSCs) for EVT.

We systematically searched PubMed, Embase, and ClinicalTrials.gov from inception to July 2, 2026. Studies comparing IVT versus no IVT prior to interhospital transfer for EVT in patients with LVO-AIS were included. Efficacy outcomes included the primary outcome of excellent functional outcome (modified Rankin Scale [mRS] 0-1 at 90 days), as well as secondary efficacy outcomes including good functional outcome (mRS 0-2 at 90 days), interhospital recanalization, and poor functional outcome (mRS 5-6). Safety outcomes included 90-day mortality, symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and parenchymal hematoma (PH). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models, and adjusted estimates were synthesized using the generic inverse variance method.

Sixteen observational studies were included. Pre-transfer IVT was associated with significantly higher rates of excellent functional outcome (OR 1.72, 95% CI 1.47-2.01, p<0.00001), good functional outcome (OR 1.64, 95% CI 1.35-1.99, p<0.00001), and interhospital recanalization (OR 7.71, 95% CI 4.08-14.55, p<0.00001), as well as significantly lower risks of poor functional outcome (OR 0.65, 95% CI 0.54-0.79, p<0.0001) and 90-day mortality (OR 0.69, 95% CI 0.59-0.81, p<0.00001). No significant differences were observed between groups in the risks of sICH (OR 0.75, 95% CI 0.50-1.11, p=0.15), any ICH (OR 0.91, 95% CI 0.76-1.09, p=0.31), or PH (OR 1.43, 95% CI 0.88-2.33, p=0.15). In the adjusted analyses, the associations remained significant for excellent functional outcome (aOR 1.47, 95% CI 1.19-1.81, p=0.0004), good functional outcome (aOR 1.61, 95% CI 1.25-2.07, p=0.0002), interhospital recanalization (aOR 8.06, 95% CI 4.71-13.82, p<0.00001), and 90-day mortality (aOR 0.64, 95% CI 0.49-0.84, p=0.001). The magnitude and direction of associations were generally consistent with the unadjusted analyses.

Among LVO-AIS patients requiring interhospital transfer from PSCs to CSCs for EVT, pre-transfer IVT was associated with improved functional outcomes and interhospital recanalization, without increasing hemorrhagic risk. These findings support pre-transfer IVT as an effective reperfusion strategy in resource‑limited settings where timely EVT is not immediately accessible.

Throughout their evolutionary trajectory, plants have orchestrated a sophisticated repertoire of defense mechanisms to counteract pathogenic threats. Central to this chemical arsenal in monocotyledonous lineages is the benzoxazinoid (BX) metabolic pathway, a quintessential secondary metabolic route that dictates plant resilience. While the biosynthetic blueprint of BXs has been extensively mapped in models such as maize (Zea mays) and wheat (Triticum aestivum), the regulatory logic and evolutionary divergence within rice (Oryza sativa) remain largely enigmatic. This review provides a high-resolution synthesis of the BX landscape, critically contrasting the canonical maize model with the emerging, yet distinct, metabolic signatures observed in rice. We contend that a comparative analysis of BX diversity is fundamental to decrypting metabolic evolution and harnessing its potential for precision crop protection. Furthermore, we evaluate the multifunctional roles of BX compounds-positioning them not merely as direct biocidal toxins, but as pivotal signaling rheostats that modulate plant defense networks and multi-trophic ecological interactions. Collectively, this synthesis establishes a robust theoretical framework for the genetic fortification of crops.