Aggressive Profile Research Articles

A Longitudinal Study of Aggression in People with Autism and Other Neurodevelopmental Disabilities.

Aggression is common in autism and neurodevelopmental disorders, but longitudinal research on aggression is lacking. We longitudinally tracked aggression in 254 individuals from toddlerhood to emerging adulthood. Our sample included participants with a range of cognitive abilities, with 39.9% classified as more-cognitively-abled (MCA; IQ ≥ 70) and 60.1% as less-cognitively-abled (LCA; IQ < 70). Aggression Composite scores were derived from data from the autism diagnostic observation schedule, autism diagnostic interview-revised, and child behavior checklist at ages 2, 9, and 18. Fifty-four percent, 69%, and 42% of the sample showed aggression in toddlerhood, school age, and emerging adulthood, respectively. LCA individuals had higher rates of aggression in school age (80%) and emerging adulthood (58%) compared to MCA individuals (48 and 22%, respectively). Longitudinal aggression profiles revealed distinct patterns of change over time: 31% displayed persistent aggression, 25% increased, 23% decreased, and 13% never displayed aggression. Higher autism symptoms, lower VIQ, NVIQ, and less-developed adaptive skills correlated with more aggression cross-sectionally. Nonverbal IQ and repetitive behaviors related to aggression longitudinally: people in decreasing or absent profiles had higher NVIQ and fewer RRBs than those with persistent or increasing profiles. Participants with aggression at 9 were four times likelier to exhibit aggression at 18. Aggression is common in autism and NDDs, peaking around age 9, and declining in emerging adulthood. Patterns of change varied widely, with evidence that higher NVIQ and fewer RRBs may be protective. Findings have implications for clinical practices, highlighting important developmental periods and high-risk subgroups.

Feasibility of the Northern Sea Route: Impact of Sea Ice Thickness Uncertainty on Navigation

With the accelerated melting of the Arctic sea ice, the opening of the Northern Sea Route (NSR) of the Arctic is becoming increasingly accessible. The purpose of this paper was to examine the impact of uncertainty in sea ice thickness (SIT) data on the opening of the NSR and to quantify the extent of this impact, which is essential to the regularized operation of polar shipping. A quantitative assessment framework was proposed to examine the influence of SIT data uncertainty on navigational uncertainty through three aspects: the navigational spatiotemporal windows, the distribution of safe sailing speeds, and the uncertainty in optimal route planning by employing four distinct SIT datasets. Furthermore, the sensitivity of navigational spatiotemporal windows, the distribution of safe sailing speeds, and route planning to variations in SIT were also evaluated. Results show that experiment results based on CS2SMOS exhibit a more aggressive profile, while results based on CPOM are more conservative. The difference in SIT data has a significant impact on the proportion of operations subject to special consideration areas, such as safety speed, sailing time, and distance in NEP. A 0.1 m discrepancy in sea ice thickness data results in an approximate 0.067 change in the proportion of operations within special consideration areas. This discrepancy also leads to an approximate speed change of 0.89 knots, a navigation duration change of approximately 4 days, and a distance change of 152 km within specified limits.

Exposure to Pesticides and Breast Cancer in an Agricultural Region in Brazil.

Rural workers are disproportionally exposed to pesticides and might be at an increased risk of developing chronic diseases. Here, we investigated the impact of pesticide exposure on breast cancer (BC) risk and disease profile in rural female workers. This is a case-control study that prospectively included 758 individuals. The study was conducted in the Southwest region of Paraná state in Brazil, a region characterized by family-based agriculture and intensive use of pesticides. We found that this region has a 41% higher BC diagnosis rate and 14% higher BC mortality rate than the mean rates in Brazil, as well as a pesticide trade volume about 6 times higher than the national average. We showed substantial exposure in this population and found that even women who did not work in the fields but performed equipment decontamination and clothes washing of male partners who worked in the fields had urine samples positive for glyphosate, atrazine, and/or 2,4-D. The crude association showed a significantly higher risk of BC among women exposed to pesticides (OR: 1.58, 95% CI 1.18-2.13). Adjusted analyses showed a lower and nonstatistically significant association (OR: 1.30, 95% CI 41 0.87-1.95). Stratification on disease profile showed a significantly higher risk of lymph node metastasis (adjusted OR: 2.19, 95% CI 1.31-3.72) in women exposed to pesticides. Our findings suggest that female populations exposed to pesticides are at a higher risk of developing BC with a more aggressive profile and draw attention to the need to monitor rural populations potentially exposed to pesticides in the field or at home.

Landscape of HER2-low breast cancer: Insights from a six-year study on incidence and clinicopathological characteristics.

e13148 Background: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+ or 2+ in immunohistochemistry (IHC) and the absence of the ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2 breast cancer to novel anti-HER2 antibody-drug conjugates, rising interest in the HER2-low subtype. To date, data on characteristics of HER2-low breast cancer subtype is limited. Herein, we describe the clinicopathological characteristics of HER2-low breast cancer subtype compared HER2-zero/negative breast cancer. Methods: Real-world data from the Anatomic Pathology Division of Hotel Dieu de France, spanning 2017-2022, was retrospectively collected. Patients with HER2-IHC 3+ and HER2-IHC 2+ with ISH-amplified (HER2-positive) were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Patients were then categorized based on their hormone receptor (HR) status. Clinicopathological characteristics between the groups were compared using a Chi-Square and Mann–Whitney U tests. Results: Out of 1195 patients, we observed 341 (28.5%) HER2-low breast cancers cases. HER2-positive breast cancer cases (n=178; 14.9%) were subsequently excluded. There was no significant difference in age and sex between the HER2-low and the HER2-zero group (p=0.3 and 0.8, respectively). HER2-low breast cancer was associated with positive estrogen receptor (ER) status and positive progesterone receptor (PR) status (p&lt;0.001 and p=0.01, respectively). Ductal adenocarcinomas were more frequently observed in the HER2-low group, whereas lobular and metaplastic adenocarcinomas were especially prevalent in the HER2-zero group (all p&lt;0.001). When stratified by HR status, 87.4% of patients had HR-positive status and 12.6% were HR-negative. Furthermore, the occurrence rate of tumors with a low Ki-67 labeling index was comparable between the two groups (p=0.9). However, among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (p = 0.04; Table). Conclusions: In conclusion, this study showed that HER2-low is a distinct from HER2-zero and is frequently present among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Our findings suggest that, within HR-negative breast cancer, breast cancer with low HER2 expression exhibits a less aggressive profile when compared to HER2-zero tumors. [Table: see text]

Landscape of HER2-low breast cancer: Insights from a six-year study on prevalence and clinicopathological characteristics

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+/2+ in immunohistochemistry (IHC) and absence of ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2-low breast cancer to novel anti-HER2 antibody-drug-conjugates. Data on characteristics of HER2-low breast cancer subtype is limited. Real-world data from the Anatomic Pathology Department of Hotel-Dieu de France, spanning 2017–2023, was retrospectively collected. HER2-positive patients were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Clinicopathological characteristics between the groups were compared using a Chi-Squared test. Out of 1195 patients, we observed 341 (28.5 %) HER2-low breast cancers cases. HER2-positive breast cancer cases (n = 178; 14.9 %) were excluded. There was no significant difference in age and sex between HER2-low and HER2-zero group (p = 0.33 and 0.79, respectively). HER2-low breast cancer was associated with positive estrogen receptor status and positive progesterone receptor status (p < 0.001 and p = 0.01, respectively). Ductal adenocarcinomas were more commonly observed in HER2-low group (p < 0.001). When stratified by hormone (HR) status, 87.4 % of patients had HR-positive status and 12.6 % were HR-negative. Among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (25%vs.10 %, p = 0.04). This study showed that HER2-low is distinct from HER2-zero and is common among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Within HR-negative breast cancer, those with low HER2 expression exhibit a less aggressive profile compared to HER2-zero tumors.

Evidence of Correlation between Pathogenicity, Avirulence Genes, and Aggressiveness of Fusarium oxysporum f. sp. cubense in Banana “Cavendish” and “Prata” Subgroups

Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is one of the most destructive diseases in banana farming worldwide. Knowledge of the factors of genetic diversity and virulence of the pathogen contributes to the development of resistant cultivars and management strategies based on exclusion. In this study, phenotypic traits such as virulence and aggressiveness in a sample of 52 Foc isolates were analyzed and their relationship to the presence of putative effectors of gene SIX (Secreted in Xylem) pathogenicity homologs was verified. The similarity matrix revealed three isolates that were closest to the standard Foc race 1 strain. Isolates 229A and 218A were selected according to their aggressiveness profile in ‘Grand Naine’ and ‘Prata-Anã’, respectively, to replace the standard isolate of race 1 in the resistance screening process carried out by the breeding program. Two homologs of the SIX8 gene, SIX8a and SIX8b, are present in isolates of Foc from Brazil, and the SIX8b gene correlates with avirulence in the cultivar ‘Grand Naine’ (Cavendish). These results are important to support the banana genetic breeding program by identifying sources of resistance to Foc and contributing to the establishment of the function of SIX effector proteins.

Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives.

Betulinic acid is a naturally occurring compound that can be obtained through methanolic or ethanolic extraction from plant sources, as well as through chemical synthesis or microbial biotransformation. Betulinic acid has been investigated for its potential therapeutic properties, and exhibits anti-inflammatory, antiviral, antimalarial, and antioxidant activities. Notably, its ability to cross the blood-brain barrier addresses a significant challenge in treating neurological pathologies. This review aims to compile information about the impact of betulinic acid as an antitumor agent, particularly in the context of glioblastoma. Importantly, betulinic acid demonstrates selective antitumor activity against glioblastoma cells by inhibiting proliferation and inducing apoptosis, consistent with observations in other cancer types. Compelling evidence published highlights the acid's therapeutic action in suppressing the Akt/NFκB-p65 signaling cascade and enhancing the cytotoxic effects of the chemotherapeutic agent temozolomide. Interesting findings with betulinic acid also suggest a focus on researching the reduction of glioblastoma's invasiveness and aggressiveness profile. This involves modulation of extracellular matrix components, remodeling of the cytoskeleton, and secretion of proteolytic proteins. Drawing from a comprehensive review, we conclude that betulinic acid formulations as nanoparticles and/or ionic liquids are promising drug delivery approaches with the potential for translation into clinical applications for the treatment and management of glioblastoma.

Dissociating the impact of alexithymia and impaired self-awareness on emotional distress and aggression after traumatic brain injury.

Alexithymia, a deficit in identifying and describing feelings, is prevalent in traumatic brain injury (TBI). Sometimes referred to as "emotional unawareness," we sought to investigate whether alexithymia after TBI was related to, or distinct from, impaired self-awareness (ISA) and whether the two predicted differentiable emotional and aggression profiles. Further, the mediating role of frontal system behaviors (disinhibition, dysexecutive function, apathy) was explored. Participants with TBI (N = 40) from diverse backgrounds completed self-report measures of alexithymia, emotional distress, aggression, and frontal system behaviors. For the assessment of ISA, significant other ratings were obtained to identify discrepancies from self-ratings. Data were analyzed quantitatively using independent samples t tests, correlations, partial correlations, and simple mediation. There was a negative correlation between alexithymia and ISA. Alexithymia, but not ISA, was associated with higher expressions of emotional distress and aggression even after controlling for the effects of ISA via partial correlations. Exploratory analyses found that frontal system behaviors mediated the relationships between alexithymia and aggression and alexithymia and emotional distress. Alexithymia is more accurately conceptualized as an emotional processing deficit than an awareness deficit. Indeed, self-awareness may be a prerequisite for the ability to identify alexithymic tendencies. Negative psychological effects of alexithymia are compounded by poorer executive function and disinhibition and call for the development of TBI-specific alexithymia screening tools and interventions. Alexithymia interventions are best delivered in conjunction with rehabilitation of emotion regulation and executive function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of male to female Japanese quail (Coturnix japonica) interactions on female´s plumage and skin condition

The high incidence of aggression in mature domestic birds is a major concern for the poultry industry. In Japanese quails, an overall score on female plumage condition was proposed to identify whether their male partner showed an aggressive profile towards them. This study delves further into the relationship between aggressive and/or sexual male Japanese quail performances and the plumage and skin condition of their female counterparts. We used an original “more rigorous” scoring system and a single female body areas approach, aiming to easily identify specific regions that are predominantly affected by male´s aggressive and/or sexual behavior and could be used to predict male´s performance. Additionally, this study investigates whether deteriorations in female plumage and skin condition induced by males when paired with a single female (1 male and 1 female) for pedigree purposes can also be similarly evidenced when females are housed for multiplication purposes in groups of 4 every 1 male. After 60 days of cohabitation, males were classified as low or highly aggressive based on the number of pecks recorded, and female skin and plumage status was evaluated. The study found significant positive correlations between male pecking and female's head and neck plumage and skin status, but no correlation between male sexual behaviors and female plumage and skin status. Using the male classification according to the extreme aggressive performance towards their female mate, females housed with highly aggressive males had worse neck plumage and head and neck skin status than females housed with low aggressive males. In addition, these highly aggressive males initiated more copulation sequences but achieved the same number of cloacal contacts as low-aggressive males. Regarding groups, highly aggressive males continued to express aggressive behaviors more frequently to the 4 females than those classified as low aggressive. It was observed that the female group housed with highly aggressive males had worse head plumage status than those housed with low aggressive males. Our findings suggest that the level of male aggressiveness can be discerned by examining the condition of the females' head and neck plumage, irrespective of whether they are housed in pairs or within groups. Plumage and skin body regions and conditions evaluated appear not useful when aiming to infer male quail sexual activity.

BDE-209 exposure in murine melanoma (B16–F1) cells modulates tumor malignancy and progression in vivo

Melanoma is a type of skin cancer considered aggressive due to its high metastatic ability and rapid progression to other tissues and organs. BDE-209 (2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether) is an additive used as a flame retardant and classified as a persistent organic pollutant that has a high bioaccumulation capacity due to its lipophilic nature. This substance has already been detected in rivers, air, soil, plants and even in different human biological samples, such as plasma, umbilical cord blood and breast milk, revealing a great concern to human populations. Thus, in the current study we investigated whether prior exposure of murine melanoma B16–F1 cells to BDE-209 modulates in vivo progression and malignancy of melanoma. B16–F1 cells were cultured and exposed in vitro to BDE-209 (0.01, 0.1 e 1 nM) for 15 days and then inoculated, via caudal vein, in C57BL/6 mice for experimental metastasis analysis after 20 days. Inoculation of BDE-209-exposed cells resulted in 82% increase of metastasis colonized area in the lungs of mice, downregulation of tumor suppressors genes, such as Timp3 and Reck, decrease of lipid peroxidation and increase of systemic and local inflammatory response. These findings are related to melanoma progression. Additionally, the histopathological analysis revealed greater number of focal points of metastases in the lungs and invasiveness of metastases to the mice brain (89%). The results showed that exposure to BDE-209 may alter the phenotype of B16–F1 cells, worsening their metastatic profile. Current data showed that BDE-209 may interfere with the prognosis of melanoma by modulating cells with less invasiveness capacity to a more aggressive profile.

Effects of genotype and host environment on the cuticular hydrocarbon profiles of Lysiphlebus parasitoids and aggression by aphid-tending ants.

Parasitoids in the genus Lysiphlebus specialize on ant-tended aphids and have previously been reported to mimic the cuticular hydrocarbon (CHC) profiles of their aphid hosts to avoid detection by ants. However, the precise mechanisms that mediate reduced ant aggression toward Lysiphlebus spp. are not known, nor is it clear whether such mechanisms are broadly effective or specialized on particular aphid hosts. Here we explore the effects of wasp genotype and host environment on Lysiphlebus CHC profiles and ant aggression. Rearing asexual Lysiphlebus lines in different host aphid environments revealed effects of both wasp line and aphid host on wasp CHCs. However, variation in genotype and host affected different features of the CHC profile, with wasp genotype explaining most variation in linear and long-chain methyl alkanes, while aphid host environment primarily influenced short-chain methyl alkanes. Subsequent behavioural experiments revealed no effects of host environment on ant aggression, but strong evidence for genotypic effects. The influence of genotypic variation on experienced ant aggression and relevant chemical traits is particularly relevant in light of recent evidence for genetic divergence among Lysiphlebus parasitoids collected from different aphid hosts.

Ultrathin lithium disilicate and translucent zirconia crowns for posterior teeth: Survival and failure modes.

To evaluate the reliability and failure modes of ultrathin (0.5 mm) lithium disilicate, translucent and ultra-translucent zirconia crowns for posterior teeth restorations. Fifty-four mandibular first molar crowns of three ceramic materials: (1) Lithium disilicate (e.max CAD, Ivoclar Vivadent), (2) 3Y-TZP (Zirconn Translucent, Vipi), and (3) 5Y-PSZ (Cercon XT, Dentsply Sirona), with 0.5 mm of thickness were milled and cemented onto composite resin abutments. Eighteen samples of each group were tested under mouth-motion step-stress accelerated life testing in a humid environment using mild, moderate, and aggressive profiles. Data was subjected to Weibull statistics. Use level curves were plotted and reliability was calculated for a given mission of 100,000 cycles at 100, 200, and 300 N. Fractographic analyses of representative samples were performed in scanning electron microscope. Beta (β) values suggest that failures were dictated by material's strength for lithium disilicate and by fatigue damage accumulation for both zirconias. No significant differences were detected in Weibull modulus and characteristic strength among groups. At a given mission of 100,000 cycles at 100 N, lithium disilicate presented higher reliability (98% CB: 95-99) regarding 3Y-TZP and 5Y-PSZ groups (84% CB: 65%-93% and 79% CB: 37&-94%, respectively). At 200 N, lithium disilicate reliability (82% CB: 66%-91%) was higher than 5Y-PSZ (20% CB: 4%-44%) and not significantly different from 3Y-TZP (54% CB: 32%-72%). Furthermore, at 300 N no significant differences in reliability were detected among groups, with a notable reduction in the reliability of all materials. Fractographic analyses showed that crack initiated at the interface between the composite core and the ceramic crowns due to tensile stress generated at the intaglio surface. Ultrathin lithium disilicate crowns demonstrated higher reliability relative to zirconia crowns at functional loads. Lithium disilicate and zirconia crown's reliability decreased significantly for missions at higher loads and similar failure modes were observed regardless of crown material. The indication of 0.5 mm thickness crowns in high-load bearing regions must be carefully evaluated. Ultraconservative lithium disilicate and zirconia crowns of 0.5 mm thickness may be indicated in anterior restorations and pre-molars. Their clinical indication in high-load requirement regions must be carefully evaluated.

A disintegrin and metalloproteinase 22 activates integrin β1 through its disintegrin domain to promote the progression of pituitary adenoma.

Approximately 35% of pituitary adenoma (PA) display an aggressive profile, resulting in low surgical total resection rates, high recurrence rates, and worse prognosis. However, the molecular mechanism of PA invasion remains poorly understood. Although "a disintegrin and metalloproteinases" (ADAMs) are associated with the progression of many tumors, there are no reports on ADAM22 in PA. PA transcriptomics databases and clinical specimens were used to analyze the expression of ADAM22. PA cell lines overexpressing wild-type ADAM22, the point mutation ADAM22, the mutated ADAM22 without disintegrin domain, and knocking down ADAM22 were generated. Cell proliferation/invasion assays, flow cytometry, immunohistochemistry, immunofluorescence, co-immunoprecipitation, mass spectrometry, Reverse transcription-quantitative real-time PCR, phos-tag SDS-PAGE, and Western blot were performed for function and mechanism research. Nude mice xenograft models and rat prolactinoma orthotopic models were used to validate in vitro findings. ADAM22 was significantly overexpressed in PA and could promote the proliferation, migration, and invasion of PA cells. ADAM22 interacted with integrin β1 (ITGB1) and activated FAK/PI3K and FAK/ERK signaling pathways through its disintegrin domain to promote PA progression. ADAM22 was phosphorylated by PKA and recruited 14-3-3, thereby delaying its degradation. ITGB1-targeted inhibitor (anti-itgb1) exerted antitumor effects and synergistic effects in combination with somatostatin analogs or dopamine agonists in treating PA. ADAM22 was upregulated in PA and was able to promote PA proliferation, migration, and invasion by activating ITGB1 signaling. PKA may regulate the degradation of ADAM22 through post-transcriptional modification levels. ITGB1 may be a potential therapeutic target for PA.

Gender and postoperative surgical margin status in MIBC: An analysis of the National Cancer Database.

4599 Background: Women with muscle-invasive bladder cancer (MIBC) continue to experience persistent disparities in health outcomes despite accounting for less than 1/3 of newly diagnosed bladder cancer cases. Multiple studies have acknowledged the aggressive profile of female bladder cancer. This study aims to identify tangible areas to intervene and improve the delivery of oncologic care. Methods: The National Cancer Database (NCDB) was queried from 2004-2017 to conduct a retrospective cohort analysis of men and women with MIBC (cT2a-T4). N=41,037 patients with MIBC were reviewed, (30,313 male; 10,724 female). The primary endpoints were OS and surgical margin status. Logistic regression was performed to determine whether female sex conferred differential impact on surgical margin status when controlling for baseline clinical stage, age, receipt of neoadjuvant chemotherapy (NAC), Charleson-Deyo Comorbidity Classification (CDCC), and facility type. Cox proportional hazards assessed the impact of age, gender, margin status, CDCC and NAC on OS. Results: Logistic regression showed that sex, age, baseline clinical stage, CDCC, facility type and NAC were significant predictors of surgical margin status (p&lt;.001). Female sex was found to have a 14.4% higher probability of having positive residual margins (HR 1.144 (95% CI: 1.07-1.23), p&lt;.001). When adjusting for age, margin status, CDCC and NAC, Female gender (OS HR 1.063 (95% CI: 1.03-1.09), p&lt;.001), positive microscopic margins (OS HR 2.0 (95% CI: 1.90-2.10), p&lt;.001) and positive macroscopic margins (OS HR 2.62 (95% CI: 2.40-2.90), p&lt;.001) independently portended poorer OS and necessitated increased adjuvant XRT (p&lt;.001). Unexpected demographic findings included a significantly greater number of females than expected with a median household income &lt;$38,000 (p= 0.047) and a greater number of females in the upper quartile of patients without a HS diploma (p&lt;.001). The median days from diagnosis to definitive surgical treatment was significantly lower compared to males (58 vs 67 days; p&lt;.001). Conclusions: Women with MIBC faced obstacles to getting treatment (less education and lower median income). Despite these hurdles they may be more proactive with their health as seen by a shorter time from diagnosis to the surgical table. However, this proactivity has yet to pay off as women undergoing surgical treatment for MIBC were significantly less likely to have clear margins post-operatively. The urologic community must mirror female patient’s proactivity and further investigate the gender disparity in surgical treatment of MIBC. [Table: see text]

Companion animals and profiles of peer social behavior in adolescence.

Relationships with companion animals have been associated with higher levels of prosocial behavior and lower levels of socioemotional difficulties for children and adolescents. Companion animals may be supportive of developing prosocial behavior in youth through practice with positive social interactions and the development of empathy and reciprocity skills. The goal of this study was to use a person-centered approach to investigate if living with a pet (including pet species) is associated with profiles of adolescent peer social behaviors (i.e., prosocial, aggressive), and size of their peer network. This study used data from the Adolescent Brain Cognitive Development (ABCD) Study®, a large, nationally representative data set of American adolescents. In a cross-sectional sample of 5218 adolescents, we found that youth clustered into four different distinct profiles of peer social behavior. Female youth living with dogs were less likely to be in the High Aggression profile as compared to youth without pets or youth with other types of pets. However, having a pet was not associated with whether youth were in the profiles characterized by prosocial behaviors or size of peer network. Overall, future research should explore how gender intersects with companion animal interactions-both in terms of frequency of interactions as well as relationship quality/emotional attachment-as well as examine these relationships over time to assess causality.

Evolutionary and neuroendocrine foundations of human aggression

Humans present a behavioural paradox: they are peaceful in many circumstances, but they are also violent and kill conspecifics at high rates. We describe a social evolutionary theory to resolve this paradox. The theory interprets human aggression as a combination of low propensities for reactive aggression and coercive behaviour and high propensities for some forms of proactive aggression (especially coalitionary proactive aggression). These tendencies are associated with the evolution of groupishness, self-domestication, and social norms. This human aggression profile is expected to demand substantial plasticity in the evolved biological mechanisms responsible for aggression. We discuss the contributions of various social signalling molecules (testosterone, cortisol, oxytocin, vasopressin, serotonin, and dopamine) as the neuroendocrine foundation conferring such plasticity.

Breast cancer and the molecular mechanism of estrogen signaling

Cancer is a complex pathology that occurs due to the uncontrolled proliferation and growth of cells in any organ or tissue of the body. Breast cancer is the most frequently diagnosed cancer among women worldwide and is the second leading cause of cancer-related deaths. Breast cancer is a pathology that exhibits heterogeneity in which genetic and environmental risk factors play a role. Although many treatment approaches have been developed for breast cancer today, the frequency of the number of patients diagnosed with breast cancer and lost their lives due to this reason is increasing in the world. The most significant limitation to the success of the treatment approaches developing drug resistance in breast cancer cells, and the disease relapses after a certain period and exhibits a more aggressive profile. Therefore, understanding the molecular biology of breast cancer is essential for developing potent therapeutic approaches. It is known that the development of breast cancer is related to changes in direct and indirect signaling mechanisms mediated by estrogen and estrogen receptor. These signaling mechanisms exhibit highly complex interaction patterns. This review summarizes the pathology of breast cancer, estrogenic compounds, estrogen receptors, genomic and non-genomic molecular signaling mechanisms mediated by estrogen and estrogen receptor.

Abstract 5235: Transcriptome-wide study of tumor samples from Peruvian women identifies dysregulated pathways in luminal tumors typically associated with more aggressive disease

Abstract Purpose: Breast cancer incidence and outcomes differ by US census racial/ethnic category. Since large-scale genetic studies of human disease are predominately focused on populations of European ancestry, little is known about breast cancer molecular biology in Hispanic/Latinos which can widen cancer health disparities due to suboptimal translation of discoveries into clinical practice or public health policy. We aim to describe relevant pathways in breast cancer subtype differentiation in breast cancer patients from Peru. Patients and Methods: Formalin fixed paraffin embedded tumor tissues samples were whole exome sequenced for a total of 271 patients, recruited by the Peruvian Breast Cancer Genomics Study (PEGEN-BC) from the Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Quality control was conducted to remove genes with low counts. Intrinsic tumor subtypes were classified using the PAM50 method using genefu package in R. Differential gene expression between subtypes was performed by DEseq2 R package and statistical significance was determined using FDR&amp;lt;0.05 for samples with at least log2 1.5-fold change. Pathway analyses were performed to explore differences among the subtypes using GSEA with fgsea package in R. Indigenous American ancestry proportions for participants were estimated using germline genome-wide genotypes and the program Admixture. Results: The mean age of patients was 50 and the median Indigenous American ancestry was 79%. PAM50 classification of the sequenced samples defined 20.2% of tumors as LumA, 27.9% as LumB, 27.1% as HER2, 22.5% as Basal and 2.3% as Normal. Transcriptomic pathway analysis showed that most of the significantly changed pathways were similar to those previously described such as upregulation of high proliferation pathways in LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Top 10 significantly changed pathways show some unique findings: the epithelial-mesenchymal-transition (EMT) pathway is downregulated in Basal, comparing to LumA and HER2 tumors, which is unexpected given that the EMT is associated with stem cell features and poor outcomes. The E2F-targets pathway is upregulated in LumA when comparing to HER2 tumors, but downregulated when compared to Basal tumors. Conclusions: We identified novel pathways associated with breast cancer subtypes in individuals with high Indigenous American ancestry from Peru and are working on testing the robustness of these findings. If our findings are confirmed, results would suggest a more aggressive profile of Luminal subtypes in the studied samples from Peru, with implications for treatment and survival. Citation Format: Chenghuiyun Xu, Valentina A. Zavala-Cordero, Xiaosong Huang, David M. Rocke, Sandro Casavilca-Zambrano, Jeannie M. Navarro-Vásquez, Carlos A. Castañeda, Guillermo Valencia, Zaida Morante, Monica Calderón, Julio E. Abugattas, Henry Gómez, Hugo A. Fuentes, Ruddy Liendo-Picoaga, Jose M. Cotrina, Silvia P. Neciosup, Katia Roque, Jule Vásquez, Luis Mas, Marco Gálvez-Nino, Jovanny Zabaleta, Tatiana Vidaurre, Laura Fejerman. Transcriptome-wide study of tumor samples from Peruvian women identifies dysregulated pathways in luminal tumors typically associated with more aggressive disease. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5235.

Peripheral immune cell profiling of double-hit lymphoma by mass cytometry

BackgroundDouble-hit or Triple-hit lymphoma (DHL/THL) is a subset of high-grade B cell lymphoma harboring rearrangements of MYC and BCL2 and/or BCL6, and usually associate with aggressive profile, while current therapies tend to provide poor clinical outcomes and eventually relapsed. Further explorations of DHL at cellular and molecular levels are in demand to offer guidance for clinical activity.MethodsWe collected the peripheral blood of DHL patients and diffused large B cell lymphoma (DLBCL) patients from single institute and converted them into PBMC samples. Mass cytometry was then performed to characterize these samples by 42 antibody markers with samples of healthy people as control. We divided the immune cell subtypes based on the expression profile of surface antigens, and the proportion of each cell subtype was also analyzed. By comparing the data of the DLBCL group and the healthy group, we figured out the distinguished immune cell subtypes of DHL patients according to their abundance and marker expression level. We further analyzed the heterogeneity of DHL samples by pairwise comparison based on clinical characteristics.ResultsWe found double-positive T cells (DPT) cells were in a significantly high percentage in DHL patients, whereas the ratio of double-negative T cells (DNT) was largely reduced in patients. Besides, CD38 was uniquely expressed at a high level on some naïve B cells of DHL patients, which could be a marker for the diagnosis of DHL (distinguishing from DLBCL), or even be a drug target for the treatment of DHL. In addition, we illustrated the heterogeneity of DHL patients in terms of immune cell landscape, and highlighted TP53 as a major factor that contributes to the heterogeneity of the T cells profile.ConclusionOur study demonstrated the distinct peripheral immune cell profile of DHL patients by contrast to DLBCL patients and healthy people, as well as the heterogeneity within the DHL group, which could provide valuable guidance for the diagnosis and treatment of DHL.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study

Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers’ immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.