Aggressive Behavior Research Articles

Evaluating microvascular invasion in hepatitis B virus-related hepatocellular carcinoma based on contrast-enhanced computed tomography radiomics and clinicoradiological factors

BACKGROUND Microvascular invasion (MVI) is a significant indicator of the aggressive behavior of hepatocellular carcinoma (HCC). Expanding the surgical resection margin and performing anatomical liver resection may improve outcomes in patients with MVI. However, no reliable preoperative method currently exists to predict MVI status or to identify patients at high-risk group (M2). AIM To develop and validate models based on contrast-enhanced computed tomography (CECT) radiomics and clinicoradiological factors to predict MVI and identify M2 among patients with hepatitis B virus-related HCC (HBV-HCC). The ultimate goal of the study was to guide surgical decision-making. METHODS A total of 270 patients who underwent surgical resection were retrospectively analyzed. The cohort was divided into a training dataset (189 patients) and a validation dataset (81) with a 7:3 ratio. Radiomics features were selected using intra-class correlation coefficient analysis, Pearson or Spearman’s correlation analysis, and the least absolute shrinkage and selection operator algorithm, leading to the construction of radscores from CECT images. Univariate and multivariate analyses identified significant clinicoradiological factors and radscores associated with MVI and M2, which were subsequently incorporated into predictive models. The models’ performance was evaluated using calibration, discrimination, and clinical utility analysis. RESULTS Independent risk factors for MVI included non-smooth tumor margins, absence of a peritumoral hypointensity ring, and a high radscore based on delayed-phase CECT images. The MVI prediction model incorporating these factors achieved an area under the curve (AUC) of 0.841 in the training dataset and 0.768 in the validation dataset. The M2 prediction model, which integrated the radscore from the 5 mm peritumoral area in the CECT arterial phase, α-fetoprotein level, enhancing capsule, and aspartate aminotransferase level achieved an AUC of 0.865 in the training dataset and 0.798 in the validation dataset. Calibration and decision curve analyses confirmed the models’ good fit and clinical utility. CONCLUSION Multivariable models were constructed by combining clinicoradiological risk factors and radscores to preoperatively predict MVI and identify M2 among patients with HBV-HCC. Further studies are needed to evaluate the practical application of these models in clinical settings.

Revisiting the Alcohol-Aggression Link: The Impact of Alcohol Consumption Patterns

Laboratory studies have repeatedly reported a link between alcohol and aggression, yet many rely on single-dose administration methods and overlook variations in alcohol consumption patterns. The present study investigates the effects of alcohol on aggressive behavior using a double-blind, placebo-controlled cumulative drinking administration approach that mirrors the natural drinking behaviors often observed in pubs within a laboratory setting. This study also pioneers the examination of how alcohol consumption patterns (light or heavy) moderate the relationship between precise Breath Alcohol Concentration (BrAC) levels and extreme aggressive behavior. Seventy-five light (N=38) and heavy (N=37) alcohol drinkers were randomly assigned to alcohol (N=33) or placebo (N=42) conditions. Participants drank four drinks successively. Taylor's aggression paradigm was completed twenty minutes after each drink. Multilevel modeling was applied to analyze the effects of precise BrAC and account for within-person variability. Alcohol showed a dose-dependent effect on aggression; as alcohol levels rose, so did aggression (p<.001). Alcohol consumption pattern moderated the effect of cumulative BrAC on aggression, such that the effect was more substantial for light as compared with individuals who drink heavily (p=.03). The current study highlights the moderating role of alcohol consumption pattern in the association between precise BrAC levels and extreme aggression, offering insights into individual differences in susceptibility to alcohol-induced aggression, and supporting the I3 meta-theory (Finkel, 2014). The Findings underscore the importance of investigating the interplay between acute and chronic alcohol use on behavior, challenging conventional thresholds for hazardous drinking classification. Implications for future studies, legislators, and policymakers are discussed.

Expression of cancer stem cell markers (CD24, CD44 & ALDH1A3 isoform) in Breast Cancer in Indian population considering clinicopathological characteristics and response to neoadjuvant chemotherapy - a prospective analysis from a university hospital.

Cancer stem cells (CSC) are a small number of tumour propagating cells present in the bulk of tumour cells. Expression of biological markers for CSCs viz. cluster of differentiation 24 and 44 (CD24, CD44) and aldehyde dehyodeganse 1 (ALDH1) imply aggressive tumour cell behaviour and poorer outcome, particularly in breast cancer. N = 75 Tumor tissue samples from enrolled breast cancer patients were obtained and subjected to histopathological examination and immunohistochemistry (IHC) after informed consent from patients. In addition to the estrogen receptor, progesterone receptor, Her2 neu receptor, and Ki67 index; IHC was also performed for CD24, CD44 and ALDH1A3 expression. These markers' positivity was correlated with clinical parameters, therapy response and metastasis prognostication. Most patients had higher tumor stage and high nodal burden (81.3% with node positivity; N1-68%, N2 -6.6%, N3-6.6%). Study showed significant association of CD24-/CD44 + group (p = 0.021) with distant metastasis and significant association of CD24-/CD44 + /ALDH1A3 + (p = 0.008) with higher stage (T4 stage). Tumor tissues expressing CD24-/CD44 + /ALDH1A3 + group (p = 0.010) and CD24 + /CD44 + / ALDH1A3 + (p = 0.010) were significantly associated with poor response to treatment. The correlation of CD24-/CD44 + was also statistically significant (p = 0.009). Positive expression of either CD24 and/or CD44 presented with aggressive disease, larger tumours and heavy nodal burden at a younger age. Additionally, ALDH1A3 positivity signified higher metastasis rates. CD24-/CD44 + /ALDH1A3 + and CD24 + /CD44 + / ALDH1A3 + correlated with greater chances of distant metastasis, aggressive disease, limited response to chemotherapy and poorer prognosis. Thus, these observations establish the role of these CSC phenotypes as important factors for prognostic outcomes and predictors of adverse outcomes. CD24-/CD44 + /ALDH1A3 + expression could serve as an important prognostic marker and predictor of adverse outcomes in Indian breast cancer tumour biology.

The associations between negative parenting and aggressive behavior: the Mediating role of normative beliefs approving aggression

The associations between negative parenting and aggressive behavior: the Mediating role of normative beliefs approving aggression

Navigating Risks in the Emergency Room: A Comprehensive Review of Patient-Related Violence Against Medical Workers in Emergency Departments

Patient-related violence against healthcare workers in emergency departments (EDs) has become a growing concern worldwide, impacting the safety and well-being of medical staff, the quality of patient care, and the overall healthcare system. This review provides a comprehensive analysis of the prevalence, types, and contributing factors of patient-related violence in ED settings, including environmental stressors, patient conditions, organizational policies, and social influences. The physical and psychological impact on ED workers, such as injury, stress, burnout, and job dissatisfaction, is also explored. Furthermore, current prevention and management strategies are reviewed, including security measures, training programs, policy frameworks, and support systems. The article identifies challenges, including underreporting and research gaps, and offers recommendations for improved reporting systems, policy reforms, and targeted training to equip ED staff to handle aggressive behavior. By highlighting these key insights, this review underscores the urgent need for evidence-based interventions to protect healthcare workers in EDs and improve workplace safety and patient care outcomes.

Abstract PR011: Efferocytic macrophage promotes pancreatic cancer liver metastasis

Abstract Pancreatic ductal adenocarcinoma (PDAC) presents a major therapeutic challenge due to its aggressive metastatic behavior. In the liver metastasis microenvironment of PDAC, macrophages are key drivers of tumor progression. Targeting these pro-tumorigenic macrophages requires a deep understanding of the various macrophage populations and the factors influencing their phenotypes. Our study has revealed a distinct subset of macrophages with a pro-tumorigenic phenotype that emerges early in PDAC liver metastasis. We found that the establishment of hepatic metastases triggers local tissue damage, which, through efferocytosis, reprograms macrophages into an immunosuppressive state, thereby facilitating metastasis. Inhibiting efferocytosis pharmacologically prevented the conversion of macrophages, enhanced CD8+ T cell responses, and reduced liver metastasis. These results highlight the role of macrophages in tissue repair processes that promote liver metastasis in PDAC and suggest potential therapeutic targets to hinder its progression. Citation Format: Yuliana Astuti, Meirion Raymant, Valeria Quaranta, Kim Clarke, Maidinaimu Abudula, Olivia Smith, Gaia Bellomo, Vatshala Chandran-Gorner, Craig Nourse, Christopher Halloran, Paula Ghaneh, Daniel Palmer, Robert Jones, Fiona Campbell, Jeffrey Pollard, Jennifer Morton, Ainhoa Mielgo, Michael Schmid. Efferocytic macrophage promotes pancreatic cancer liver metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR011.

Effects of self-compassion on aggression and its psychological mechanism through perceived stress.

Given the increasing global concerns about aggressive behaviors and the pressing need for effective psychological interventions, this study delves into the potential of a concept deeply rooted in positive and Buddhist psychology but largely researched in Western contexts, as a mitigating factor against aggression in Chinese adults. Through three core studies involving 652 participants (age: 30.52±8.16), our research illuminated the intricate relationship between self-compassion, perceived stress, and aggression. Study 1 identified a negative correlation among these variables, setting the empirical foundation. In Study 2, participants exposed to a self-compassion exercise reported enhanced self-compassion and reduced aggression. Study 3 further consolidated these findings, with participants in the self-compassion writing group, showing notable increases in self-compassion and decreases in aggression compared to a control group. Critically, perceived stress emerged as a significant mediator between self-compassion and aggression, elucidating its central role in this dynamic. Together, our findings underscore the promise of self-compassion as a strategy to curb aggression tendencies, especially in light of its influential relationship with perceived stress, suggesting vital implications for future mental health interventions.

Characterization of Breast Cancer Intra-Tumor Heterogeneity Using Artificial Intelligence

Intra-tumor heterogeneity (ITH) is a fundamental characteristic of breast cancer (BC), influencing tumor progression, prognosis, and therapeutic responses. However, the complexity of ITH in BC makes its accurate characterization challenging. This study leverages deep learning (DL) techniques to comprehensively evaluate ITH in early-stage luminal BC and provide a nuanced understanding of its impact on tumor behavior and patient outcomes. A large cohort (n = 2561) of early-stage luminal BC was evaluated using whole slide images (WSIs) of hematoxylin and eosin-stained slides of excision specimens. Morphological features of both the tumor and stromal components were meticulously annotated by a panel of pathologists in a subset of cases. A DL model was applied to develop an algorithm to assess the degree of heterogeneity of various morphological features per individual case utilizing defined patches. The results of extracted features were used to generate an overall heterogeneity score that was correlated with the clinicopathological features and outcome. Overall, 162 features were quantified and a significant positive correlation between these features was identified. Specifically, there was a significant association between a high degree of intra-tumor heterogeneity and larger tumor size, poorly differentiated tumors, highly proliferative tumors, tumors of no special type (NST), and those with low estrogen receptor (ER) expression. When all features are considered in combination, a high overall heterogeneity score was significantly associated with parameters characteristic of aggressive tumor behavior, and it was an independent predictor of poor patient outcome. In conclusion, DL models can be used to accurately decipher the complexity of ITH and provide extra information for outcome prediction.

Single-cell transcriptomics link gene expression signatures to clinicopathological features of gonadotroph and lactotroph PitNET.

Pituitary neuroendocrine tumors (PitNET) are among the most common intracranial tumors. Despite a frequent benign course, aggressive behavior can occur. Tumor behavior is known to be under the influence of the tumor microenvironment (TME). However, the relationship between TME cells and aggressive tumor behavior has not been adequately explored in PitNET. We performed differential expression analysis as well as gene expression program identification based on single-cell RNA sequencing to comparatively characterize the transcriptome of seven gonadotroph and three lactotroph PitNET and correlate it with clinical features using bulk RNA-seq data from an independent cohort of 134 PitNET. Tumor immune infiltration was quantified via immunostaining on tissue sections of gonadotroph and lactotroph PitNET. In lactotroph PitNET, we detect a highly proliferative gene profile with significantly increased expression levels in aggressively growing tumors within bulk RNA-seq data of an independent cohort of 134 PitNET samples. We also report high intratumoral heterogeneity in gonadotroph PitNET (GoPN) and lactotroph PitNET (LaPN) and identify signatures of epithelial, endocrine, and immunological gene networks in both subtypes. A comparison of their TME composition shows enrichment of SPP1+ macrophages and CD4+ T cells in GoPN, as well as enrichment of CD4/CD8 double-negative T cells (DN) and natural killer cells (NK) in LaPN. Also notable is the presence of proliferative lymphocytes, the occurrence of which positively correlates with more aggressive tumor behavior in the bulk RNA-seq cohort. However, increased CD8+ T and NK cell abundances correlate significantly with reduced aggressiveness indicating potential anti-tumoral effects. Our study expands the knowledge of the differences in cellular composition of gonadotroph and lactotroph PitNET subtypes. It lays the foundation for further studies on the influence of lymphoid cells on the variable aggressive behavior of PitNET. Regarding the treatment of drug-resistant lactotroph PitNET, proliferative lymphocytes, CD8+ T, and NK cells could represent potentially valuable targets for developing new cancer immunotherapies.

Robotic Total Anatomical Left Hepatectomy with En Bloc Caudate Resection and Systematic Portal Lymphadenectomy for Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is the second most common primary liver cancer with an aggressive behavior and poor prognosis.1,2 The only potential curative option is radical resection, traditionally undertaken via an open operation.3,4 Reports on minimally invasive approach are sparse and limited. In this video, we described our technique for robotic total anatomical left hepatectomy with en bloc caudate resection for an intrahepatic cholangiocarcinoma involving segment 1 and dorsal aspect of segment.4 METHODS: A 78-year-old man presented to our office with a caudate lobe mass infiltrating dorsal aspect of left hepatic lobe. CT scan of abdomen/pelvis showed a large caudate lobe mass, consistent with an intrahepatic cholangiocarcinoma. No evidence of extrahepatic metastasis was seen. The operation was undertaken by using a robotic platform with 5 ports. An intraoperative ultrasound was used to mark the location of the middle hepatic vein to be preserved while securing R-0 parenchymal margins. Operation time was 4.5 hours with 100 cc blood loss. The postoperative course was uneventful, and the patient was discharged home on postoperative day 6. Pathological results showed moderately differentiated cholangiocarcinoma of Caudate lobe (6.7 cm) with two additional satellite lesions in the left hepatic lobe (0.5 cm, 0.7 cm). Background liver tissue showed congested sinusoids and minimal macrovesicular steatosis negative for significant cholestasis, inflammation, or fibrosis. 1/13 hilar lymph nodes was involved by carcinoma. We demonstrated a safe, feasible, and reproducible technique of robotic total anatomical left hepatectomy with en bloc caudate resection and portal lymphadenectomy for intrahepatic cholangiocarcinoma.

Personality and Interpersonal Influence: Low Adjustment and Low Competitiveness is Associated With Low Assertiveness.

This study examined the relationship between personality and interpersonal assertiveness styles, an important and neglected topic. In all, 396 working adults completed a six-factor personality test measuring work-related traits (HPTI) and a two-dimensional assessment of interpersonal styles (III) assessing four styles: Assertiveness, Passiveness, Hostile aggression, and Manipulative aggression. We were particularly interested in the correlates of aggressive and passive behaviour, as opposed to assertive behaviour. The results suggested that those with low Conscientiousness and Adjustment (i.e. Neuroticism) but high Competitiveness (low Agreeableness) were more interpersonally aggressive, while passivity was negatively associated with all traits, particularly Adjustment, but not with Conscientiousness. Regressions indicated very different traits associated with each of the four interpersonal styles. Assertiveness was associated with sex and age, but only one trait, Risk Approach (or Courage). Limitations of these findings and implications of assessing and teaching assertiveness are discussed and considered.

TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer.

Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes. This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group. Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic β-catenin. RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

Clinicopathologic feature and treatment progress of high-grade ovarian neuroendocrine tumors.

High-grade Ovarian neuroendocrine tumors represent a rare subset of ovarian neoplasms characterized by aggressive behavior, poor prognosis, and early metastasis. Despite their clinical significance, the management of these tumors lacks consensus due to their low incidence. This comprehensive review encompasses literature spanning from 1991 to 2024, focusing on the clinical presentation, diagnostic criteria, differential diagnosis, prognostic indicators, treatment modalities, and recent advancements in the understanding of this condition. Notably, a substantial proportion of affected individuals present during the perimenopausal period with unilateral lesions displaying mixed histological components. Biomarkers such as CA125, CA199, and NSE hold promise for aiding in the diagnosis and screening of ovarian neuroendocrine tumors. Unfortunately, patients exhibit a dismal prognosis even diagnosed at an early stage. Primary treatment strategies predominantly involve surgical intervention coupled with etoposide-cisplatin combination chemotherapy. In cases of recurrence, second-line chemotherapeutic agents including paclitaxel, irinotecan, and doxorubicin are commonly employed alongside localized radiotherapy. While specific genetic mutations remain elusive, emerging evidence suggests potential therapeutic effect involving mTOR inhibitors, PD-1 monoclonal antibodies, and antiangiogenic agents based on isolated case reports. The exploration of representative set of mutations will help for precise targeted therapies and remains a focal point of our ongoing research efforts.

Endocervical Adenocarcinoma With Micropapillary Component, a Distinct Histological Subtype Associated With Aggressive Behavior and Poor Prognosis: A Clinicopathologic Study of 10 Patients.

Objective. Endocervical adenocarcinoma (ECA) with a micropapillary component is considered to be associated with aggressive behavior and poor prognosis. So far, only limited studies investigated this histological subtype of ECA in the literature. In this study, we present a clinicopathological analysis of 10 such tumors. Methods. We retrieved ten ECAs with a micropapillary component between January 2014 and July 2023 and analyzed their clinicopathologic features. Results. At diagnosis, nine tumors (90%) were of advanced clinical stage (FIGO stage ≥ IIA), nine tumors (90%) exhibited deep stromal invasion (≥2/3 of the cervix), and three tumors (30%) showed parametrial involvement. Lymphovascular invasion was evident in all tumors (100%), and lymph node metastasis was found in eight tumors (80%). Among the 10 patients, six were alive without disease (60%), one had a recurrent/later metastatic tumor (10%), and three died from the disease (30%). Furthermore, eight tumors were positive for PD-L1 expression (80%), while only one tumor showed HER2 overexpression (10%), and one tumor exhibited p53 mutant-type staining (10%). Conclusion. Endocervical adenocarcinomas with micropapillary components are associated with aggressive clinical behavior and a poor prognosis, which can be found in various conventional histological types of ECAs regardless of the HPV status. The high prevalence of PD-L1 expression suggests that patients with micropapillary ECAs may be good candidates for PD-L1 inhibitor treatment.

Characteristics of temper tantrums in 1-6-year-old children and impact on caregivers.

Temper tantrums are common behavioral difficulties in children. Although they are generally considered a normal part of development, certain characteristics-such as aggression, prolonged duration, and frequent occurrences-have been linked to psychological issues and can negatively impact both the child and their caregivers. To study the prevalence and characteristics of temper tantrums in children aged 1-6 years at daycare and in kindergarten in Thailand as well as the impact of problematic and non-problematic tantrums on their caregivers' emotional well-being. This cross-sectional descriptive study was conducted in 2021. The main caregivers of the participants completed self-reported questionnaires that collected their demographic information and the temper tantrum characteristics and impacts on the caregivers' emotions. Data from 211 children were included in this study. The mean child age was 4.4 ± 1.2 years. Two hundred and one (95.3%) parents reported that their children had at least one tantrum behavior, of which verbal were the most common (94.5%). One hundred and eleven (55.2%) children had tantrums defined as problematic: exhibiting aggressive physical behavior, duration >15 min, frequency > 3 days/week. The mean emotional burden scores of the children's problematic and non-problematic temper tantrums on their parents were 23.3 ± 8.4 and 17.7 ± 8.3 (maximum, 55; p = 0.001), respectively, showing a statistically significant difference. Tantrums are common in children aged 1-6 years, but their expression varies. Problematic tantrums were reported for approximately half of the children and significantly impacted their caregivers' emotions. Therefore, children with problematic tantrums and their families should receive assistance.

A Review of Limbic System-Associated Membrane Protein in Tumorigenesis

Purpose of Review: This review aims to describe the role of limbic system-associated membrane protein (LSAMP) in normal- and pathophysiology, and its potential implications in oncogenesis. We have summarized research articles reporting the role of LSAMP in the development of a variety of malignancies, such as clear cell renal cell carcinoma, prostatic adenocarcinoma, lung adenocarcinoma, osteosarcoma, neuroblastoma, acute myeloid leukemia, and epithelial ovarian cancer. We also examine the current understanding of how defects in LSAMP gene function may contribute to oncogenesis. Finally, this review discusses the implications of future LSAMP research and clinical applications. Recent Findings: LSAMP has been originally described as a surface adhesion glycoprotein expressed on cortical and subcortical neuronal somas and dendrites during the development of the limbic system. It is categorized as part of the IgLON immunoglobulin superfamily of cell-adhesion molecules and is involved in regulating neurite outgrowth and neural synapse generation. LSAMP is both aberrantly expressed and implicated in the development of neuropsychiatric disorders due to its role in the formation of specific neuronal connections within the brain. Additionally, LSAMP has been shown to support brain plasticity via the formation of neuronal synapses and is involved in modulating the hypothalamus in anxiogenic environments. In murine studies, the loss of LSAMP expression was associated with decreased sensitivity to amphetamine, increased sensitivity to benzodiazepines, increased hyperactivity in new environments, abnormal social behavior, decreased aggressive behavior, and decreased anxiety. Findings have suggested that LSAMP plays a role in attuning serotonergic activity as well as GABA activity. Given its importance to limbic system development, LSAMP has also been studied in the context of suicide. In malignancies, LSAMP may play a significant role as a putative tumor suppressor, the loss of which leads to more aggressive phenotypes and mortality from metastatic disease. Loss of the LSAMP gene facilitates epithelial-mesenchymal transition, or EMT, where epithelial cells lose adhesion and gain the motile properties associated with mesenchymal cells. Additionally, LSAMP and the function of the RTK pathway have been implicated in tumorigenesis through the modulation of RTK expression in cell membranes and the activation of second messenger pathways and β-catenin. Summary: Beyond its many roles in the limbic system, LSAMP functions as a putative tumor suppressor protein. Loss of the LSAMP gene is thought to facilitate epithelial-mesenchymal transition, or EMT, where cells lose adhesion and migrate to distant organs. LSAMP’s role in modulating RTK activity and downstream ERK and Akt pathways adds to a large body of data investigating RTK expression in oncogenesis. The characteristics of LSAMP defects and their association with aggressive and metastatic disease are evident in reports on clear cell renal cell carcinoma, prostatic adenocarcinoma, lung adenocarcinoma, osteosarcoma, neuroblastoma, acute myeloid leukemia, and epithelial ovarian cancer.

Artificial meerkat algorithm: a new metaheuristic algorithm for solving optimization problems

Abstract In this study, a novel artificial meerkat optimization algorithm (AMA) is proposed to simulate the cooperative behaviors of meerkat populations. The AMA algorithm is designed with two sub-populations, multiple search strategies, a multi-stage elimination mechanism, and a combination of information sharing and greedy selection strategies. Drawing inspiration from the intra-population learning behavior, the algorithm introduces two search mechanisms: single-source learning and multi-source learning. Additionally, inspired by the sentinel behavior of meerkat populations, a search strategy is proposed that combines Gaussian and Lévy variations. Furthermore, inspired by the inter-population aggression behavior of meerkat populations, the AMA algorithm iteratively applies these four search strategies, retaining the most suitable strategy while eliminating others to enhance its applicability across complex optimization problems. Experimental results comparing the AMA algorithm with seven state-of-the-art algorithms on 53 test functions demonstrate that the AMA algorithm outperforms others on 71.7% of the test functions. Moreover, experiments on challenging engineering optimization problems confirm the superior performance of the AMA algorithm over alternative algorithms.&amp;#xD;

The expression of keratin 17 and p27 predicts clinical outcomes in colorectal cancer.

Keratin 17 (K17) is frequently overexpressed, associated with poor prognosis in various cancers, and contributes to p27 degradation during cancer progression. Using immunohistochemistry, we evaluated K17 and p27 expression and assessed their biological behavior and prognostic significance in 326 colorectal cancers. High K17 expression was associated with poorly differentiated tumors, high pT classification, and lymph node metastases. Low p27 expression was associated with large tumors, high pT classification, lymphovascular invasion, and lymph node metastases. The overall survival of patients with high K17 expression was significantly worse than that of patients with low K17 expression [hazard ratio (HR) = 1.805, 95% confidence interval (CI) 1.169-2.787; p = 0.007]. Patients with low p27 expression showed significantly worse overall survival than those with high p27 expression (HR = 3.082, 95% CI 1.722-5.517; p < 0.001). When combining the results of K17 and p27 expression, the K17highp27low expression group showed the worst overall survival. On the contrary, the K17high/lowp27high group showed the best overall survival (p < 0.001). Therefore, K17highp27low expression is an independent poor prognostic factor in colorectal cancer. Thus, high K17 and low p27 expression correlate with aggressive clinicopathologic behavior and can be used as poor prognostic markers in colorectal cancer.

PATH-43. MALIGNANT TRANSFORMATION OF MENINGEAL MELANOCYTOMA - GENETIC ALTERATIONS AND RESPONSE TO CHECKPOINT BLOCKADE IMMUNOTHERAPY

Abstract INTRODUCTION Meningeal melanocytomas are uncommon tumors that develop from leptomeningeal melanocytes. These tumors can exhibit aggressive behavior, leading to symptoms due to compression and potential invasion of nearby central nervous tissue. Case: In this report, we discuss the case of a 45-year-old man who was diagnosed 18 years ago with a meningeal melanocytoma in the right temporal region. He underwent complete resection with each recurrence and received focal intensity-modulated radiation therapy after a third recurrence in 2013. In May 2022, he developed progressive headaches and diplopia secondary to tumor recurrence on the right temporal region. Resection revealed that the tumor had progressed to malignant meningeal melanoma with 34 mitoses per 10 high-power fields. Next-generation sequencing (NGS) showed GNAQ mutation confirming tumor of central nervous system (CNS) origin, and also showed an SF3B1 mutation, indicating aggressive behavior. Several chromosomal abnormalities were also detected. Systemic workup revealed liver, lung, and bone metastasis. Liver biopsy confirmed meningeal melanoma of central origin. The patient received radiosurgery with a total of 30Gy over five fractions to intracranial surgical cavity, followed by three cycles of nivolumab and relatlimab. Unfortunately, the patient experienced severe intracranial and systemic progression, leading to his death six months after the malignant transformation. DISCUSSION Meningeal melanocytomas are rare however these tumors have a high recurrence rate with potential malignant transformation over time. NGS is a valuable tool for confirming the CNS origin of the tumor and predicting its aggressive behavior. Despite microscopic similarity with cutaneous melanomas, meningeal melanocytomas have different pathogenesis and do not seem to respond to immunotherapy, as observed in this case.

Morphological and Optical Profiling of Melanocytes and SK-MEL-28 Melanoma Cells Via Digital Holographic Microscopy and Quantitative Phase Imaging.

Melanoma, which originates from pigment-producing melanocytes, is an aggressive and deadly skin cancer. Despite extensive research, its mechanisms of progression and metastasis remain unclear. This study uses quantitative phase imaging via digital holographic microscopy, Principal Component Analysis (PCA), and t-distributed Stochastic Neighbor Embedding (t-SNE) to identify the morphological, optical, and behavioral differences between normal melanocytes and SK-MEL-28 melanoma cells. Our findings reveal significant differences in cell shape, size, and internal organization, with SK-MEL-28 cells displaying greater size variability, more polygonal shapes, and higher optical thickness. Phase shift parameters and surface roughness analyses underscore melanoma cells' uniform and predictable textures. Violin plots highlight the dynamic and varied migration of SK-MEL-28 cells, contrasting with the localized movement of melanocytes. Hierarchical clustering of correlation matrices provides further insights into complex morphological and optical relationships. Integrating label-free imaging with robust analytical methods enhances understanding of melanoma's aggressive behavior, supporting targeted therapies and highlighting potential biomarkers for precise melanoma diagnostics and treatment.