Aggressive riding behavior is a key contributing factor to road accidents, particularly in motorcycling, where rider dynamics directly influence vehicle stability and control. Despite growing interest in objective behavioral assessment, validated classification frameworks specific to motorcycles remain scarce in the literature. This pilot study investigated the feasibility of a standard deviation-based method for classifying aggressive riding behavior in a single experienced motorcyclist navigating two distinct environments: an urban route (UR) and a suburban national route (SNR). The participant completed two 20 min rides under real-world conditions. The UR was characterized by frequent accelerations, braking, speed bumps, and traffic lights, whereas the SNR features low traffic density and minimal interruptions. Longitudinal acceleration data were continuously recorded using a Vicon Blue Trident measurement unit mounted on the motorcycle seat. Drawing on the threshold principles established in automotive research, an environment-specific classification framework was developed to categorize riding events into normal, aggressive, and dangerous levels for both acceleration and deceleration maneuvers. The derived thresholds revealed pronounced environmental differences: UR thresholds (acceleration: 2.122 m/s2; deceleration: -2.134 m/s2) were approximately three times lower than those observed in the SNR (acceleration: 6.16 m/s2; deceleration: -7.09 m/s2). From more than four million recorded data points, approximately 88% of the riding behavior was classified as normal in both routes. In the UR, 9.27% of events were identified as aggressive and 4.37% as dangerous, compared with 7.27% aggressive and 5.35% dangerous events in the SNR. These preliminary findings suggest that environment-specific thresholds may be essential for accurately characterizing motorcycle riding behavior, and caution against the direct application of fixed automotive criteria to motorcycle safety analyses. All findings are specific to one rider on two routes and must not be extrapolated to other motorcyclists, vehicle types, or road contexts without replication.
To explore the relationship between family trauma, school bullying and adolescent suicidal behavior, and the regulatory role of DRD2 gene polymorphism. A total of 98 adolescent patients with depressive disorders who visited our hospital from June 2022 to June 2024 were selected. They were divided into the non-suicide group (n=62) and the suicide group (n=36) based on their suicide behavior in the previous 6 months and their attitudes towards suicide behavior. The general data of the two groups were compared. The relationship between each genotype and suicide behavior, the influencing factors of suicide behavior, the interaction between family trauma and school bullying on suicide behavior, and the regulatory effects of depression and genetic polymorphisms were analyzed. The possible regulatory effects of depression and genetic polymorphisms were also investigated. Compared with the non-suicide group, the duration of illness, non-suicidal self-harm behavior, family trauma, school bullying, anxiety, depression scores in the suicide group increased, while the life meaning score decreased (P < 0.05). The genotype A2A2 was associated with an increased risk of suicidal behavior compared to genotype A1A1 (P < 0.05). In the recessive model, the genotype A2A2 was associated with an increased risk of suicidal behavior compared to genotype A1A1 and A1A2 (P < 0.05); in the additive model, there were significant associations between the genotypes A1A1, A1A2, A2A2 and suicidal behavior (P < 0.05). Non-suicidal self-harm behavior, family trauma, school bullying, depression, and the A2A2 genotype were independent risk factors for suicidal behavior, while life meaning was an independent protective factor. Family trauma > 54.78 points and school bullying > 10.37 points had a multiplicative (OR=6.585, 95%CI: 5.478-7.367) and additive (OR=7.849, 95%CI: 7.231-8.294) interaction effect on adolescent suicidal behavior. Depression exerted a regulatory effect between family trauma (β=0.092, 95%CI: 0.084-0.103), school bullying (β=0.090, 95%CI: 0.081-0.098) and suicidal behavior. In the additive genetic model, the TaqⅠA gene had a significant regulatory effect on "family trauma, school bullying → depression → suicidal behavior" in adolescents with the A1A2/ A2A2 genotype. The risk of suicidal behavior is higher in adolescents with both family trauma and school bullying, and depression plays a part of the mediating effect. The TaqⅠA polymorphism of DRD2 gene has a significant regulatory effect on adolescents carrying A2 allele.
Current data on neuroendocrine tumors (NETs) of the gallbladder and cystic duct (GB-NETs) are highly limited, and the available evidence, largely derived from cancer registry data, suggests that these tumors exhibit a substantially more aggressive clinical behavior than NETs arising at other anatomical sites. We analyzed 26 GB-NETs. Female-to-male ratio: 1.9:1; median age: 50 years. They were typically incidental small (median: 0.8 cm, range: 0.08-2.3 cm) tumors, with 81% classified as grade 1 (G1), either pT1 or pT2, and 38% showing a paraganglioma-like pattern at least focally. Body/fundus tumors were mostly polypoid while neck/cystic duct examples showed mural growth. Symplastic pleomorphism was found in 11%, pseudoglandular structures in 50% and psammomatous intraluminal calcifications in 15%. Pancreatic polypeptide, somatostatin, and gastrin were detected in 5/7 (71%), 5/8 (62.5%), and 4/7 (57%) tested cases, respectively. ISLET1 and ARX were diffusely expressed in all 5 tested cases. Cholesterolosis was common, and six appeared to arise within cholesterol polyps. None had any evidence of metastasis and all 12 patients with available follow-up were alive without disease after a median follow-up of 30 months. Critical review of the literature (79 bona-fide GB-NETs) showed that tumors > 2 cm and grade 3 (G3) were enriched among metastatic GB-NETs. In conclusion, GB-NETs are generally indolent neoplasms, in contrast to gallbladder neuroendocrine carcinomas. Tumor size and grade may help predict metastatic potential, while the relatively frequent paraganglioma-like morphology, often associated with diffuse somatostatin expression, can represent a diagnostic pitfall. Their frequent association with cholesterol polyps also suggests a possible etiopathogenetic link.
Pathological aggression often results from the interaction between early-life adversity and later psychosocial stress. Maternal separation (MS) is an early-life stress model that increases vulnerability to aggression. However, social isolation (SI) is a paradigm for inducing aggressive behaviors and anterior cingulate cortex (ACC) alterations. Yet, the relationship between MS to adult behavior and ACC structure, and the modulatory role of SI during adolescence, remain unclear. This study examined the effects of MS, with or without SI, on aggression, anxiety, sensory sensitivity, and ACC morphology. Swiss albino pups underwent MS (4 h/day, PND2-20) and were later housed at PND46 for two weeks under standard or isolated conditions, which resulted four groups per sex: MS-/SI-, MS+/SI-, MS-/SI+, and MS+/SI+. Behavioral assessments were conducted in adulthood (PND60-62). The Resident-Intruder test indicated increased aggression exclusively in MS+/SI+ males, while social behavior declined in both sexes of MS+/SI- and MS+/SI+. The elevated plus maze showed increased anxiety specifically in MS+/SI+ females. Mechanical allodynia, assessed by the von Frey test, was observed in MS+/SI- and MS+/SI+ groups, with no changes in thermal sensitivity measured by the hot plate test. Morphological analyses using Nissl and Golgi-Cox staining revealed ACC alterations in MS+/SI- and MS+/SI+ mice of both sexes, including reduced neuronal density, shorter dendritic length, diminished branching, lower spine density, and decreased arborization complexity of pyramidal neurons. These results highlight a synergistic effect between MS and SI: MS predisposes individuals to SI's detrimental impact, while SI amplifies MS induced behavioral and neurobiological alterations. The ACC emerges as a critical substrate mediating the cumulative effects of stress on pathological aggression and its comorbidities.
This study evaluated the effects of locally sourced ingredient dietary, with or without supplementation of black soldier fly (Hermetia illucens; BSF) larvae, on laying hen welfare. A total of 150 Lohman White hens aged 30 weeks were assigned to three treatments over ten weeks: a standard corn-soybean diet (CONTROL), an alternative diet incorporating triticale, faba beans and rapeseed meal (ALTER), and the ALTER diet supplemented with 5% dried BSF larvae provided separately (ALTER + BSF). Welfare assessments included larvae consumption time, a novel object test, an avoidance distance test, body condition scoring, and ethological observation of natural behaviors. Hens fed ALTER diet initially showed increased incidence of comb pecking wounds, which declined over the trial, along with reduced morning grooming compared to the CONTROL group (p = 0.009). However, the ALTER diet significantly improved plumage cleanliness (p < 0.001). Supplementation with BSF larvae partially mitigated early stress responses, maintained plumage cleanliness, and improved exploratory behavior and habituation to novelty (p < 0.001). Hens showed sustained and increased motivation to consume BSF larvae with an average consumption time of 5.5 min. Additionally, BSF supplementation was associated with increased resting and the emergence of dustbathing behavior during the afternoon (p < 0.05). No aggressive behaviors were observed, and no significant dietary effects were found for human fearfulness throughout the trial. In conclusion, dried BSF larvae can serve as effective environmental enrichment, improving hens' adaptability to locally sourced diets in rural farming systems.
Corticotroph adenomas include functioning tumors causing Cushing disease (CD) and silent corticotroph adenomas (SCA), which differ markedly in size, clinical presentation, and aggressiveness. The molecular basis for these differences remains incompletely understood. To characterize genomic and transcriptomic alterations underlying the divergent clinical behavior of CD and SCA. Thirty-eight tumors from 34 patients underwent whole-exome sequencing, copy-number variation (CNV) analysis, and mRNA sequencing. Molecular findings were integrated with clinical, radiological, and pathological data. USP8/USP48 mutations were present in 10 of 21 CD tumors (48%) and were associated with low CNV levels, minimal invasion, and favorable post-operative remission. In contrast, five of 13 SCAs harbored TP53/ATRX/DAXX mutations, all had markedly elevated CNV, and aggressive clinical features. Transcriptomic analysis identified an ATRX-FAM138A mRNA fusion, resulting in loss of ATRX expression in an aggressive tumor. Unsupervised transcriptome analyses defined four clusters. All USP8/USP48-mutant CD clustered together had low CNV and low recurrence rates. Cluster 2 consisted of a mixture of CD and SCA, with intermediate CNV and non-aggressive behavior. Cluster 3 included USP8-wildtype CD with heterogeneous yet generally non-aggressive courses. Cluster 4 represented high-CNV tumors enriched for TP53/ATRX/DAXX alterations, with the highest rates of radiological invasion, persistent disease, and recurrence or progression. Across the cohort, higher CNV was significantly associated with parameters of aggressiveness. Corticotroph adenomas comprise distinct molecular subtypes. USP8/USP48-mutant CD represents a low-CNV, low-risk group, whereas tumors harboring TP53/ATRX/DAXX mutations exhibit high CNV and aggressive clinical behavior. CNV and mutation profiling may assist in postoperative risk stratification.
Sexually selected weapons used in intra-sexual competition for mates are among the most striking animal features, but how their evolution affects life history traits closely correlated with fitness, and hence species' evolutionary trajectories, is not well understood. Here, we selected for or against male morphs carrying a lethal weapon in a male-dimorphic mite Sancassania berlesei, and investigated how life histories evolve in populations with high vs. low proportion of weaponized, aggressive males called fighters and non-weaponized, non-aggressive males called scramblers. After 25 generations of experimental evolution, females from fighter-selected lines showed higher early-life fecundity compared to females from lines selected for non-aggressive scrambler males. Furthermore, both sexes matured earlier in fighter-selected lines compared to scrambler-selected ones. Larvae-to-adult survivorship was not affected by such selection treatment. Finally, we investigated whether adult survivorship under temperature stress was influenced by such selection treatment, and we found no difference between fighter-selected and scrambler-selected lines. Our results demonstrate that composite selection pressures resulting from the prevalence of costly intra-sexual aggression lead to an increase in key components of fitness, with likely consequences for population dynamics. However, we found no evidence that the response to such selection affects how individuals cope with environmental challenge.
REM sleep behavior disorder (RBD) in Parkinson's disease (PD) marks a more aggressive subtype. While mitochondrial dysfunction, iron deposition, and neuromelanin loss are central to PD pathobiology, their contributions to RBD in PD remain unclear. This study noninvasively compared brain bioenergetics, phospholipid metabolism, iron accumulation, and neuromelanin integrity across PD patients with RBD (PD-RBD), without RBD (PD-noRBD), and healthy controls (HCs) to identify RBD-related metabolic alterations. Twenty-six PD-RBD, 46 PD-noRBD, and 48 HCs were recruited consecutively. All participants underwent 3T MRI, including phosphorus-31 MR spectroscopic imaging (31P-MRSI), quantitative susceptibility mapping (QSM), and neuromelanin-sensitive MRI (NM-MRI), all acquired in a standardized OFF-medication state (≥12 h withdrawal). Phosphorus metabolites included phosphoethanolamine (PE), total adenosine triphosphate (tATP), phosphodiester (PDE), and others. Group differences and associations with clinical scales were analyzed, and PD subtype discrimination performance was assessed using ROC analysis. PD-RBD patients demonstrated right basal ganglia metabolic alterations characterized by elevated α-ATP/Pi (p = 0.003 vs HCs) and PCr/Pi ratios (p = 0.001 vs HCs), together with reduced PE-related phospholipid turnover indices, including lower PE/tATP relative to PD-noRBD (p = 0.003). In contrast, PD-noRBD showed milder alterations primarily involving high-energy phosphate metabolism compared with HCs, whereas phospholipid turnover remained relatively preserved. No significant differences in iron or neuromelanin measures were observed between PD-RBD and PD-noRBD groups. However, both PD subgroups showed significantly reduced neuromelanin-related contrast in the substantia nigra compared to HCs. PE/tATP (R = -0.350, p < 0.01) and PE/PDE ratios (R = -0.441, p < 0.001) were negatively correlated with RBD symptom severity across the PD cohort. 31P-MRSI demonstrated superior discrimination performance (AUC = 0.80) compared with QSM (AUC = 0.72) or NM-MRI (AUC = 0.69), while multimodal integration achieved the highest diagnostic accuracy (AUC = 0.86). These findings support a role for altered bioenergetic and membrane phospholipid metabolism in PD-RBD and highlight 31P-MRSI as a promising imaging approach for characterizing PD heterogeneity.
Anger is a significant problem for military veterans with posttraumatic stress disorder (PTSD). Interventions designed to treat PTSD have been shown to decrease anger, which may be associated with improvements in psychosocial functioning. Couple-based PTSD treatments, which target both PTSD and relationship functioning, may be particularly useful for improving anger and associated psychosocial functioning. Thus, the current study sought to examine whether decreases in veterans' and partners' anger following participation in a brief couple-based treatment for PTSD (brief Cognitive Behavioral Conjoint Therapy for PTSD) is associated with improvements in psychosocial impairment and relationship satisfaction, in addition to decreases in suicidal ideation. The sample included 184 veterans and their intimate partners (92 dyads). Each partner completed measures assessing several aspects of anger (angry temperament, angry reaction, and psychological aggression). Veterans also completed measures assessing their psychosocial impairment, relationship satisfaction, and suicidality. Latent growth curve models tested whether changes in anger over the course of treatment were associated with corresponding changes in veterans' functional outcomes at the within-person and between-person levels. Findings showed that improvements in veterans' anger were associated with improvements in their psychosocial impairment and relationship satisfaction over time. Partners' psychological aggression was also associated with improvements in veterans' psychosocial impairment over time. Neither veterans' nor partners' anger was associated with veterans' suicidality. Findings add to the literature demonstrating that improvements in anger for both veterans and their partners in the context of PTSD treatment may be associated with improvements in broader psychosocial functioning for veterans.
Dog aggression toward humans represents a relevant public health issue. In Italy, small animal veterinarians are expected to contribute to the early identification of at-risk situations and to aggression prevention. This study aimed to assess, through a nationwide survey, veterinarians' perception of this role, regulatory awareness, and clinical practices related to dog aggression prevention in Italy. A cross-sectional study was conducted between November 2025 and February 2026 using an anonymous online questionnaire disseminated through provincial veterinary boards to private veterinarians working in small animal practice. A total of 1088 valid responses were analyzed using descriptive, inferential, and multivariable analyses. Almost all respondents reported frequent encounters with aggressive behavior, with more than 60% managing at least five aggressive dogs per year. Although 80% recognized an active preventive role for veterinarians, only 55% were aware of the current Ministerial Ordinance and 19% had ever submitted a report to public veterinary services. Specific training in behavioral medicine was independently associated with greater regulatory awareness and reporting behavior. Strong support also emerged for mandatory owner training and early behavioral assessment. A substantial gap persists between the preventive role assigned to veterinarians and the practical implementation of preventive tools. These findings support the need for strengthened behavioral medicine training and improved integration between private practitioners and public veterinary services.
Mechanisms that coordinate appropriate behavioral responses to social competition are important for both sexes. Males in many species show a seasonal peak in baseline circulating testosterone (T) concentrations at times when social challenges are more frequent with additional acute elevation in T following competitive interactions. Females in some species show the same patterns, while others do not, making females interesting test cases to evaluate these mechanisms. Here we used three approaches to investigate the interrelationship among circulating T, social challenge, and aggression in female northern house wrens (Troglodytes aedon), a species where female aggression confers a variety of fitness benefits. First, we compared circulating T concentration after a simulated territorial intrusion to T in unchallenged females to determine if T responds to social challenge. Second, we compared T concentrations between females that responded to simulated female intrusions with different levels of aggressive intensity to determine if aggressive behavior relates to T concentrations. Third, we compared natural T concentrations across breeding stages to determine if T is elevated during stages when competition is most common. Overall, female circulating T concentrations were quite low. Neither social challenge nor breeding stage had any impact on T concentrations. Likewise, the intensity of a female's aggressive response to simulated female intruders was unrelated to T. Our results indicate that house wrens may be one of a growing number of species where females mediate competitive behavior through alternative circulating signals or local mechanisms at target tissues.
Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm, most commonly affecting the epiphyseal region of long bones. Involvement of the hand bones is rare and is known to exhibit more aggressive behavior with higher recurrence rates compared to conventional sites. Optimal reconstruction following tumor excision in the hand remains challenging, as, along with the reconstruction of the bone defect, the function of the hand should also be addressed. A 19-year-old right-hand-dominant female presented with a progressively enlarging, painful swelling over the dorsum of the right hand. Radiological evaluation revealed an expansile, lytic lesion involving the ring finger metacarpal with cortical breach. Magnetic resonance imaging showed an aggressive lesion with soft-tissue involvement. Histopathological examination confirmed the diagnosis of GCT of bone. The patient underwent wide excision of the tumor followed by reconstruction using a non-vascularized autologous cortical bone graft from the ulna. GCT of the metacarpal is rare and requires aggressive surgical management due to its high recurrence potential. Non-vascularized ulnar bone graft provides a reliable, simple, and effective reconstructive option following tumor excision.
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Tumors carrying activating epidermal growth factor receptor (EGFR) mutations initially respond to tyrosine kinase inhibitors (TKIs), with Osimertinib representing the current standard of care. However, acquired resistance inevitably develops, involving both genetic and non-genetic mechanisms, the latter playing a major role in sustaining cellular plasticity and promoting tumor aggressiveness. Here, we show that Osimertinib-resistant H1975 cells acquire a more aggressive phenotype than their parental (Par) counterparts, characterized by enhanced migratory behavior and transcriptional enrichment of BMI1 target genes, as well as mitotic defects and concomitant alterations in expression of mitotic cell-cycle pathways. Despite unchanged proliferation, resistant cells display increased mitotic activity and frequent cytokinetic defects, revealing a dependency on mitotic machinery and microtubule integrity, an Achilles' heel created by adaptive resistance. Functionally, BMI1 overexpression in Par cells recapitulates both resistance and enhanced migration, highlighting its central role in driving the resistant phenotype. Exploiting these vulnerabilities, Unesbulin (PTC596), a tubulin-binding agent with BMI1 inhibitory activity, triggers mitotic catastrophe, mechanistically induces apoptosis in vitro and drives regression of resistant xenografts in vivo. Our findings establish BMI1 as a key mediator of Osimertinib resistance and aggressiveness, uncovering a mutation-context-dependent mitotic vulnerability that can be therapeutically exploited, providing a rationale for targeting BMI1 and mitotic abnormalities to overcome resistance in T790M/L858R backgrounds.
Adolescent depression and anxiety are major public health concerns. Aggression is frequently associated with internalizing symptoms, but the behavioral and body related mechanisms underlying this association remain insufficiently clarified. This study examined a theoretically proposed chain mediation model linking aggression with depressive and anxiety symptoms through internet addiction and somatization. A cross-sectional survey was conducted among 5,307 high school students in Chongqing, China. Participants filled in the Buss and Perry Aggression Questionnaire (BPAQ), Internet Addiction Test (IAT), Patient Health Questionnaire - 15 (PHQ - 15), Patient Health Questionnaire - 9 (PHQ - 9) and Generalized Anxiety Disorder Scale - 7 (GAD - 7). Regression based chain mediation analyses with 5,000 bootstrap samples were performed using PROCESS Model 6, with gender and age controlled as covariates. The results showed that aggression was positively correlated with depressive symptoms (β = 0.256, p < 0.001) and anxiety symptoms (β = 0.275, p < 0.001). Chain mediation analysis showed that aggression was indirectly associated with mental health through three distinct pathways: 1. the independent mediating effect of internet addiction; 2. the independent mediating effect of somatization; 3. the sequential chain mediating effect from internet addiction to somatization. The model explained more variance in depressive symptoms (R² = 58.2%) than in anxiety symptoms (R² = 53.5%). Furthermore, the association between somatization and depressive symptoms (β = 0.457) was stronger than that between somatization and anxiety symptoms (β = 0.428). This study supports a statistically significant chain mediation pattern in which aggression is associated with depressive and anxiety symptoms through internet addiction and somatization. The findings suggest that somatization may represent an important body related correlate in the association between maladaptive digital behavior and emotional distress, with a slightly stronger association observed for depressive symptoms than for anxiety symptoms. These findings highlight the importance of integrated school based interventions that address digital behavior regulation, somatic symptom monitoring, and emotional distress among adolescents with higher aggressive tendencies.
Digital technologies, which are widely used today, are increasingly associated with the facilitation of violence-related behaviors. The aim of this study was to determine the relationship between smartphone addiction and cyberdating abuse, and some of the factors influencing this relationship. Descriptive and cross-sectional study. The sample of the study consisted of all students studying in the nursing department of a state university in a province located in the Mediterranean region of southern Turkey. The total sample size required for the research was determined as 224. "Personal Information Form", "Smartphone Addiction Scale Short Form" and "Cyber Dating Abuse Scale" were used as data collection tools. The data was analyzed using descriptive statistics, Pearson Correlation test. Two Mann-Whitney U, Independent-t tests, Kruskal Wallis and One-Way Anova test. The study followed the STROBE reporting guideline. Of the participants, 50.9% were aged 18-20 years, 72.3% were female, 25.9% were third-year students, and 94.9% were single. The mean Smartphone Addiction Scale score was 28.30 ± 9.97, and the mean Cyber Dating Abuse Scale score was 56.30 ± 26.39. A weak but statistically significant positive relationship was found between smartphone addiction and all sub-dimensions of cyber dating abuse, including exposure to monitoring/control (r = 0.287, p = 0.003), exposure to direct aggression (r = 0.291, p < 0.001), exposure to violence (r = 0.278, p < 0.001), monitoring/control behaviors (r = 0.199, p = 0.003), direct aggression behaviors (r = 0.231, p < 0.001), and violence behaviors (r = 0.287, p < 0.001). A weak but statistically significant positive relationship was found between smartphone addiction and cyber dating abuse. Not applicable.
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal gastrointestinal cancers, and reliable preoperative predictors of aggressive tumor biology are essential for optimizing treatment strategies, particularly in resectable PDAC (RPDAC). This retrospective study evaluated the diagnostic accuracy of dynamic computed tomography (CT) for detecting extrapancreatic extension, peripancreatic plexus (PL), serosal (S), and retroperitoneal (RP) invasion, and assessed its prognostic significance. Methods: Ninety-four patients who underwent curative-intent upfront surgery for resectable PDAC between 2007 and 2020 were included. Dynamic CT was reviewed using standardized window settings (WL 35/WW 350) to identify soft-tissue projections extending beyond the pancreatic contour. Results: Pathological S, RP, and PL invasion occurred in 29.8%, 56.3%, and 17.0% of patients, respectively. Dynamic CT demonstrated accuracies of 73.4%, 76.6%, and 87.2% for S, RP, and PL invasion, respectively. Notably, patients with PL-positive CT findings had significantly poorer disease-specific survival (DSS) than those with PL-negative, with 3- and 5-year DSS rates of 37% and 0% versus 61% and 53% (p < 0.001). Multivariate analysis confirmed preoperative PL invasion as the only independent predictor of poor prognosis. Conclusions: Dynamic CT provides reasonable diagnostic performance for assessing extrapancreatic invasion. In addition, CT-identified PL invasion reflects aggressive tumor behavior and may justify consideration of neoadjuvant therapy, even in anatomically resectable disease.
Uterine smooth muscle tumors (USMTs) represent a diverse group of neoplasms arising from the myometrium, ranging from benign uterine fibroids (leiomyomas) to highly aggressive uterine leiomyosarcoma. While genetic alterations contribute to tumor development, growing evidence highlights the crucial role of epigenetic regulation in shaping tumor behavior. Among these mechanisms, histone modification has emerged as a key regulator of chromatin structure and gene expression. Histone modifications, including acetylation, methylation, phosphorylation, ubiquitination, ADP-ribosylation, and SUMOylation, are dynamically controlled by epigenetic regulators known as writers, erasers, and readers, which collectively modulate transcriptional programs involved in cell proliferation, differentiation, and stress responses. Recent studies indicate that dysregulation of histone-modifying enzymes contributes to the pathogenesis of USMTs by altering chromatin accessibility and transcriptional networks. In uterine fibroids, histone modifications are associated with hormone-responsive signaling pathways, extracellular matrix deposition, and abnormal smooth muscle cell proliferation. In contrast, uterine leiomyosarcoma exhibits extensive epigenetic reprogramming characterized by aberrant histone acetylation and methylation patterns, dysregulated chromatin regulators, and activation of oncogenic signaling pathways that promote tumor aggressiveness and genomic instability. Importantly, histone modifications interact with other epigenetic mechanisms, including DNA methylation, non-coding RNA-mediated regulation, and RNA epitranscriptomics, forming complex networks that influence tumor initiation and progression. This narrative review summarizes current knowledge on histone modification pathways and their roles in USMT biology, highlighting the functions of histone-modifying enzymes, their interactions with other epigenetic mechanisms, and their impact on tumor development. In addition, this review discusses emerging therapeutic strategies targeting epigenetic regulators, including inhibitors of histone deacetylases, histone methyltransferases, and readers, as well as potential epigenetic biomarkers for diagnosis and prognosis. Finally, this review outlines future research directions, including multi-omics integration, and advanced epigenomic technologies, which may provide deeper insights into the epigenetic landscape of USMTs and facilitate the development of personalized therapeutic approaches.
Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric neoplasm defined by SMARCB1/INI1 loss, and primary orbital involvement is rare. A 20-month-old girl presented with rapidly progressive left proptosis. Magnetic resonance imaging demonstrated a 2.1 × 1.3 × 1.6 cm temporal retrobulbar mass with focal bone erosion. The primary tumor was treated with piecemeal excision, followed by adjuvant chemoradiotherapy. Pathology showed large epithelioid tumor cells with rhabdoid morphology. Immunohistochemistry revealed diffuse expression of vimentin, CK, and CD34, but INI1 loss and SALL4 negativity. Fluorescence in situ hybridization confirmed a heterozygous SMARCB1 deletion. However, rapid local progression with extension into the temporal lobe occurred 3 months after completion of the treatment. Salvage therapy led to marked radiographic regression, but was discontinued due to severe cytopenias. The patient died of intracranial progression 34 months after the initial surgery. Orbital MRT can exhibit an atypical CD34-positive and SALL4-negative immunophenotype. The tumor demonstrates highly aggressive behavior, and adjuvant chemotherapy and radiotherapy may provide only temporary control.
Autism is characterized by differences in social functioning and many autistic individuals exhibit co-occurring features, such as aggression. While previous research has examined correlations between aggression and social skills cross sectionally, research is needed to better understand the interrelations between these behaviors over time. In a sample of 280 autistic children (ages 6-11 years), parallel process growth modeling and regression were used to examine changes in social skills and aggression across three time points, as well as the interrelations between social skills and aggression. A confirmatory factor analysis (CFA) was also conducted on the measure of aggression (the Aberrant Behavior Checklist), which yielded separate factors for aggression towards others and self-injurious behaviors (SIB). Over time, aggression towards others decreased and social skills improved, but SIB did not change. While initial levels of social skills, aggression towards others, and SIB were inter-related, there were no significant relations between initial scores and subsequent changes in any domain. Interventions for aggression in school-aged autistic children should consider aggression towards others, SIB, and social skills as separate targets, as changes in one domain did not appear to be related to changes in other domains.
To examine the effects of an intervention (Reentry Continuum for Brain Injury; (RCBI)), designed to support individuals with traumatic brain injury (TBI) pending release from prison. RCBI starts about six- months prior to release. Aims were to examine the impact of RCBI on: 1) recidivism up to 3 years post-release; and 2) participants' behavioral infractions, self-efficacy, aggression, negative attributions, and executive functioning while still incarcerated. Randomized controlled trial (RCT) comparing RCBI to treatment as usual (TAU). Assessments times: Time 1 (∼ 6 month from pre-release); Time 2 (near release); Time 3 (2 weeks post-release); and Times 3, 4, and 5 (1, 2, and 3 years post-release, respectively). Department of Corrections and Community setting. Males with TBI who were incarcerated and between eight and five months of release (n=91; RCBI=45; TAU=46). RCBI teaches brain injury coping skills and anger management while incarcerated, and 12-months of Resource Facilitation immediately following release. 1) Recidivism (reincarceration, arrests, and criminal charges) 2) Brain Injury Coping Skills Questionnaire (BICS-Q; self-efficacy; 3) Aggression Questionnaire (AQ); Ambiguous Intentions Hostility Questionnaire (AIHQ); Behavioral Rating Inventory of Executive Function-Adult Version (BRIEF-A). Compared to TAU, RCBI participants had significantly lower rates of returning to prison (46% vs 17%), arrests (86% vs 43%), and criminal charges resulting in prison or jail time (79% vs 42%) 3 years post-release. Behavioral infractions while in prison decreased over time for both groups but were significantly less for RCBI participants after the intervention compared to the TAU arm. While controlling for baseline scores, the RCBI arm had significantly better BICS-Q and BRIEF-A outcomes compared to TAU participants. No differences were observed on the AQ or AIHQ. Individuals with TBI are overrepresented in the justice system and susceptible to recidivism. RCBI improved successful community re-integration following prison in this TBI sample.