The Displaced Aggression Questionnaire (DAQ) assesses the trait tendency to aggress against innocent targets, following unrelated provocation. In a primary aim, interpersonal concepts and methods and other measures were used to evaluate the construct validity of DAQ subscales (i.e., angry rumination, revenge planning, behavioral displaced aggression). A second aim evaluated the extent to which partialing altered interpersonal and other correlates of the DAQ subscales. A representative online sample of 999 U.S. adults completed the DAQ, interpersonal circumplex measures of trait social behavior and problems, agentic and communal values, negative interpersonal experiences, social support, loneliness, and subjective social status, as well as measures of self-regulatory processes. In Structural Summary Method analyses, DAQ subscales had expected associations with hostile interpersonal style and more severe interpersonal problems. Additional correlations with interpersonal processes and self-regulation generally supported predictions. However, partialing DAQ subscales from each other severely undermined this otherwise supportive evidence of construct validity.

Myxofibrosarcoma is a rare malignant soft tissue sarcoma, typically arising in the extremities of elderly patients and exceptionally involving the head and neck region. Infraorbital localization is particularly uncommon and poses a diagnostic challenge due to the complex anatomy of the midface and the broad differential diagnosis in this region. We report the case of a 50-year-old man with a progressively enlarging, painless left infraorbital mass over 3 months. Contrast-enhanced maxillofacial computed tomography revealed a heterogeneous soft-tissue lesion with peripheral enhancement, central necrosis, subtle infiltration of adjacent fat planes, and smooth scalloping of the anterior maxillary sinus wall without cortical destruction. These findings raised suspicion of malignancy despite the relatively well-circumscribed appearance of the lesion. The patient underwent complete surgical excision with negative margins and reconstruction using a Mustardé cheek rotation flap. Histopathology confirmed a high-grade myxofibrosarcoma. Postoperative adjuvant radiotherapy was administered. At 6-month follow-up, no recurrence was observed. This case highlights an important radiological teaching point: smooth bone scalloping without cortical destruction does not exclude malignancy. Subtle imaging features such as necrosis, heterogeneous enhancement, and infiltration of adjacent fat planes may represent critical clues to aggressive behavior and should prompt careful evaluation.

This paper reports initial findings from a pilot study of the Coping Power-Rural program with upper elementary and middle school students, which was created to meet the specific needs of rural populations. Coping Power-Rural included adapted content to ensure it was relevant and accessible to students and teachers in rural schools. The program followed a two-tiered delivery format, incorporating both universal classroom sessions as well as targeted group sessions. The program also promoted skill generalization across contexts (e.g., school and home settings) through a flexible, technology-enhanced caregiver component, which provided caregivers with remote access to resources and supports. Building on prior feasibility and acceptability work (Nguyen et al. in Sch Ment Health 16:776-792, 2024. 10.1007/s12310-024-09632-2), this pilot study reports pre-post contrast testing of the Coping Power-Rural program in six rural schools across three states, involving 185 students (grades 4-7; 55.1% male; 43.2% Black; 7.6% Latine) and 48 school-based staff. The pre-post pilot outcomes indicated significant improvements in student conduct problems, aggressive/disruptive behavior, prosocial behavior, emotion regulation problems, internalizing problems, family stability, and family involvement from pretest to posttest (p < 0.05; Cohen's ds ranged from 0.20 to 0.48). There were also significant pre-post improvements for youth who participated in the targeted group on several teacher-reported outcomes (e.g., greater reductions in aggressive/disruptive behavior, emotion regulation problems, internalizing problems). These pre-post pilot findings provide promising evidence regarding outcomes for students based on exposure to the classroom Coping Power-Rural sessions, as well as for students in the targeted group.

Thymic epithelial tumors (TETs) are rare and heterogeneous malignancies whose aggressive epithelial states and microenvironmental organization remain poorly defined. Here, we integrated single-cell RNA sequencing, spatial transcriptomics, multiplex immunofluorescence, bulk transcriptomics, functional assays, xenograft validation, and computational pathology to characterize malignant epithelial heterogeneity in TETs. We identified a CDH3-associated malignant epithelial state located at the origin of malignant-state trajectories and enriched for stem-like and EMT-related features. Spatial transcriptomics and multiplex immunofluorescence showed that CDH3+ tumor cells preferentially localized within an M2 macrophage-rich immunosuppressive niche, while cell-cell communication analyses nominated CCN2-LRP1 as a candidate epithelial-myeloid crosstalk axis. A 68-gene CDH3-associated signature stratified TCGA-THYM into biologically distinct subgroups with differences in survival, histology, genomic instability, and immune contexture. Patient-derived thymic carcinoma organoids showed elevated CDH3 expression, and CDH3 silencing suppressed thymic carcinoma cell proliferation, migration, invasion, EMT/PI3K-Akt-related signaling, and macrophage-associated crosstalk. Candidate inhibitors showed antitumor activity in xenograft models. We also established a deep learning pathology model that captured CDH3-associated morphology from routine H&E slides and predicted patient outcome. Together, these findings define CDH3 as a biomarker and therapeutic target linking malignant epithelial plasticity to immunosuppressive niche formation and adverse clinical behavior in TETs.

Medical students are rarely given structured opportunities to explore how persons with disabilities (PwD) experience subtle discrimination, especially in clinical or academic settings. Despite the inclusion of disability-related competencies in medical school curriculum, microaggressions remain insufficiently addressed. This activity sought to create a reflective, immersive learning space to sensitize first-year medical students to microaggressions against PwD through a 2-day cinemeducation-based intervention.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by an immunosuppressive tumor microenvironment and resistance to chemotherapy. Previous studies have indicated that apolipoprotein C-II (APOC2) is involved in the immune microenvironment of several malignancies and is upregulated in breast cancer; however, the molecular mechanisms through which APOC2 regulates the immune microenvironment in TNBC remain poorly understood. In the present study, we found that APOC2 was upregulated in TNBC tissues and was negatively correlated with M1 macrophage infiltration. APOC2 overexpression in 4 T1 cells promoted tumor progression by enhancing cell proliferation, migration, and invasion, while suppressing M1 macrophage polarization. In addition, KLHL1, a substrate adaptor for the Cullin3-RING E3 ubiquitin ligase complex, was found to interact with APOC2, and KLHL1 overexpression reversed the biological effects induced by APOC2. Mechanistically, KLHL1 promoted APOC2 protein degradation through the ubiquitin-proteasome pathway, thereby enhancing M1 macrophage polarization and suppressing the malignant behavior of tumor cells. Finally, in vivo xenograft experiments demonstrated that APOC2 reduced M1 macrophage polarization and increased tumor weight and volume, whereas KLHL1 overexpression counteracted the oncogenic effects of APOC2. Collectively, these findings reveal that activation of the KLHL1/APOC2 axis enhances M1 macrophage polarization and inhibits TNBC progression, providing novel insights into the immune regulatory mechanisms underlying TNBC development.

Sleep loss is a well-recognized trigger of aggression and emotional dysregulation, yet it remains unclear whether its effect on aggressive behavior interacts with social hierarchy. Here, we investigated how acute sleep deprivation (ASD) modulates offensive and defensive aggression in dominant versus subordinate male mice and explored the underlying neural mechanisms. Adult ICR mice were subjected to 12-hour overnight ASD, followed by the resident-intruder test (RIT) for offensive aggression, the defensive aggression test (DAT), and the social dominance test (SDT). ASD selectively increased the total attack time in the RIT without affecting defensive aggression or altering social rank. When stratified by social rank, ASD significantly enhanced offensive aggression in dominant, but not subordinate, mice. c-Fos immunofluorescence revealed that ASD reduced neuronal activation in the medial prefrontal cortex (mPFC) while increasing it in the paraventricular nucleus (PVN). In dominant mice, ASD further increased c-Fos expression in the ventrolateral ventromedial hypothalamus (VMHvl) and PVN, with PVN activation positively correlating with attack duration. Chemogenetic inhibition of PVN neurons using hM4Di completely reversed the ASD-induced enhancement of offensive aggression. These findings demonstrate that ASD rapidly and selectively potentiates offensive aggression in dominant individuals via PVN-dependent mechanisms, revealing a critical interaction between sleep loss and social hierarchy. This study provides new insights into the neurobiological basis of sleep-related violence and suggests that targeting the PVN or sleep regulation may offer novel intervention strategies for aggression control.

Sharp-force fatalities represent a major proportion of homicidal deaths in South Africa, yet the contribution of alcohol and drugs of misuse and abuse to these incidents remains poorly characterised. This retrospective, cross-sectional study reviewed 248 sharp-force fatalities admitted to a large urban forensic service in Cape Town during 2024. Demographic, injury, and toxicological data were extracted from forensic records, and post-mortem blood and urine specimens were analysed using validated headspace gas chromatography for alcohol and liquid chromatography-tandem mass spectrometry targeting 29 drugs. Blood alcohol was detected (>0.01 g/100 mL) in 66.1% of tested cases, while 140 cases (56.5%) were positive for at least one drug. The most frequently identified analytes were 11-nor-9-carboxy-tetrahydrocannabinol (29.0%), methaqualone (27.0%), and methamphetamine (25.8%). Polydrug use occurred in 57.6% of drug-positive cases, most commonly involving methaqualone and methamphetamine, demonstrating a recurrent stimulant-sedative co-use pattern. Of the 140 drug-positive cases, 72 (51.4%) had blood alcohol concentrations below 0.05 g/100 mL, including those with no detectable alcohol, indicating that alcohol was unlikely to have been a major contributing factor in many of these fatalities. These findings demonstrate that psychoactive substances are frequently detected in individuals who die from sharp-force injuries and suggest that intoxication, particularly involving multiple substances, may contribute to impaired judgment, aggression, or increased vulnerability to violence. The results underscore the importance of comprehensive post-mortem toxicological investigations and the integration of toxicological patterns into violence-prevention initiatives and public health strategies.

Aggression is an evolutionarily conserved behavior essential for survival and reproduction, yet escalation to high-intensity forms entails substantial metabolic costs and injury risks, necessitating precise neural control. Using Drosophila melanogaster, we uncovered a multilayered inhibitory circuit that constrains aggressive escalation. This circuit involves a cotransmitting octopamine-glutamate ventral paired medial 4 (VPM4) neuron and its downstream GABAergic target, MBON-11. Neurotransmitter-specific manipulations reveal that octopamine and glutamate release from VPM4 is independently regulated by presynaptic OAα2R and mGluR receptors, providing transmitter-specific feedback. Postsynaptically, glutamate inhibits the approach-promoting MBON-11 neuron via GluClα receptors, restraining transitions to high-intensity aggression and supporting a role in approach/avoidance behaviors. Furthermore, the Rdl GABAergic receptor within MBON-11 neurons provides rapid inhibitory feedback, creating an additional layer of regulation. Together, these findings reveal a circuit architecture in which cotransmission and inhibitory feedback loops form a layered inhibition mechanism that continuously constrains escalation, indicating that aggression intensity is actively regulated to align behavior with context and cost-benefit trade-offs.

It is known that prolonged cell passaging may affect the outcomes of cell-based experiments. This study aimed to comprehensively investigate the consequences of long-term culture of U87MG glioblastoma cells, focusing on cell metabolism, morphology, tumorigenicity and drug response. U87MG (L) cells subjected to long-term culturing (20 passages) displayed altered morphology and significantly enhanced autofluorescence of lipofuscin, a well-established marker of oxidative stress and cellular senescence, compared with control U87MG cells maintained for only 5 passages. Fluorescence-lifetime imaging microscopy (FLIM) of NADH revealed the metabolic shift likely associated with glycolysis in long-term cultured U87MG (L) cells. Using the genetically encoded sensor HyPer7, the increase in basal intracellular levels of hydrogen peroxide in U87MG (L) cells was detected. In vivo studies employing orthotopic intracranial xenotransplantation in immunodeficient NSG mice revealed that, unlike short-term cultured U87MG cells, which formed visible tumor nodules with clearly delineated margins, long-term cultured U87MG (L) cells infiltrated diffusely into brain tissues, invaded bone tissue, and exhibited perineural growth. Such an aggressive behavior resulted in worse survival outcomes of xenograft-bearing mice. Notably, U87MG (L) cells became less susceptible to temozolomide, but acquired sensitivity to death receptor 5 (DR5)-selective variant of cytokine TRAIL in vitro and in vivo due to increased DR5 expression on the cell surface and downregulation of cFLIP expression. Our findings with the U87MG cell line indicate that culture duration can alter cellular responses, thereby impacting experimental outcomes. It should be carefully considered when establishing tumor models and evaluating efficacy of potential drug candidates.

Antisocial behaviour in youth has serious consequences at individual and societal level. Adolescence is also a critical period for the emergence of prodromal psychosis symptoms. Their co-occurrence may aggravate aggression and lead to severe adverse outcomes. Common genetic risk for psychosis, antisocial behaviour, and substance use has been suggested, but the putatively shared genetic architecture is unknown, and evidence in youth is limited. Here we examined whether common genetic liability indexed by polygenic risk scores (PRSs) relates to these complex traits in the Norwegian Mother, Father and Child Cohort Study (MoBa; n = 18960). Antisocial psychopathology was operationalised as three complementary dimensions: conduct-disorder (CD) traits, oppositional-defiant disorder (ODD) traits, and psychopathy traits. We first quantified phenotypic correlations between psychotic-like experiences (PLEs) and the antisocial dimensions. We then evaluated PRS-phenotype associations (single-PRS and joint multivariable models) using PRSs for antisocial behaviour (PRSASB) and schizophrenia (PRSSCZ), in addition to PRS for alcohol use disorder (PRSAUD). We found phenotypic correlations between antisocial traits and PLEs (rs=0.13-0.34, p < 0.0001). This overlap was reflected at the genetic level, as we found associations between PRSASB and PLEs (p = 0.0004). The associations between PRSSCZ and antisocial traits were present for CD (p = 0.005) and ODD (p = 0.003) traits. Both PLEs and antisocial traits were associated with PRSAUD. Patterns persisted in mutually adjusted models. These findings indicate cross-trait associations between polygenic liability for SCZ, ASB, AUD and adolescent PLEs and antisocial dimensions in the general youth population, consistent with partially shared common genetic influences. Future studies should further delineate underlying biological mechanisms.

As human activities intensify, many freshwater environments are becoming darker. Suspended sediments released by human-mediated erosion and manufactured dyes discharged into waterways act as pollutants that alter the visual environment. These substances absorb and refract light, reducing visibility levels and potentially interfering with animal behaviors such as predator avoidance, foraging, and social organization. Predicting the effects of such visual pollutants in the environment is complicated by the temporal variability of pollutant levels due to factors such as rainfall and wastewater flow. Here, we compared how an exposure to stable versus fluctuating levels of suspended sediments and dye respectively altered the social, movement, and anxiety-like behaviors of captive zebrafish (Danio rerio). We found that fish moved more when exposed to fluctuating dye concentrations but decreased their movement when exposed to a stable suspended sediment concentration. Aggression decreased under stable exposures to both pollutants, but fluctuating conditions counteracted these effects. In contrast, shoaling behavior increased when fish were exposed to either pollutant regardless of fluctuation. This suggests that zebrafish may have different movement strategies for moving through turbid and dyed environments and that low visibility likely increases zebrafish shoaling. We also performed an optomotor response (OMR) assay to assess zebrafish visual perception under the different experimental conditions. While our OMR assays did not reveal any clear effects of either pollutant on visual perception, the fish performed fewer anxiety-like behaviors during the low visibility OMR assays. This suggests that low visibility may reduce stress during stressful events. Overall, our results reveal that visual pollution influences the behavior of fish, and that both the variability and type of pollutant influence behavioral responses.