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The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays a crucial role in driving tumor progression, shaping treatment responses, and influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) tumor stroma, highlighting its key constituents and their dynamic contributions. We examine how significant changes within the cSCC ECM—specifically, alterations in fibronectin, hyaluronic acid, laminins, proteoglycans, and collagens—promote cancer progression, metastasis, and drug resistance. The cellular composition of the cSCC TME is also explored, detailing the intricate interplay of cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, and various immune cell populations. These diverse players modulate tumor development, angiogenesis, and immune responses. Finally, we emphasize the TME’s potential as a therapeutic target. Emerging strategies discussed in this review include harnessing the immune system (adoptive cell transfer, checkpoint blockade), hindering tumor angiogenesis, disrupting CAF activity, and manipulating ECM components. These approaches underscore the vital role that deciphering TME interactions plays in advancing cSCC therapy. Further research illuminating these complex relationships will uncover new avenues for developing more effective treatments for cSCC.

The pathological implication of amyloid precursor protein (APP) in Alzheimer's disease has been widely documented due to its involvement in the generation of amyloid-β peptide. However, the physiological functions of APP are still poorly understood. APP is considered a multimodal protein due to its role in a wide variety of processes, both in the embryo and in the adult brain. Specifically, APP seems to play a key role in the proliferation, differentiation and maturation of neural stem cells. In addition, APP can be processed through two canonical processing pathways, generating different functionally active fragments: soluble APP-α, soluble APP-β, amyloid-β peptide and the APP intracellular C-terminal domain. These fragments also appear to modulate various functions in neural stem cells, including the processes of proliferation, neurogenesis, gliogenesis or cell death. However, the molecular mechanisms involved in these effects are still unclear. In this review, we summarize the physiological functions of APP and its main proteolytic derivatives in neural stem cells, as well as the possible signaling pathways that could be implicated in these effects. The knowledge of these functions and signaling pathways involved in the onset or during the development of Alzheimer's disease is essential to advance the understanding of the pathogenesis of Alzheimer's disease, and in the search for potential therapeutic targets.

Background and objectives: The pineal gland is a photoneuroendocrine organ in the midline of the brain, responsible primarily for melatonin synthesis. It is composed mainly of pinealocytes and glial tissue. This study examined human postmortem pineal glands to microscopically assess age-related changes using digital techniques, and offers a perspective on evolutionary tendencies compared to the past. Materials and Methods: A retrospective autopsy study has been performed on 72 pediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with glial fibrillary acidic protein (GFAP). Slides were assessed under polarized light and digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. Results: Thirty-three females and 39 males were included in the study, grouped under three age groups: 0–25, 46–65, and 66–96 years of age. The peak gland volume was found within the 46–65 age group, the overall mean volume was 519 mm3, the main architectural types were lobular and insular, and the mean percentage of pineal calcification was 15% of the gland, peaking within the 66–96 age group, with a predominantly globular shape. Glial cysts were found in 20.8% of cases. The intensity of GFAP stain was maximal in the pediatric age group, but the extent of glial tissue was much larger in elderly patients. Discussion: The degenerative process of the pineal gland can be quantified by measuring normal parenchyma, calcifications, glial tissue, and glial cysts. Morphometric differences have been observed and compared to a similar studies performed in the published literature. The current study, unfortunately, lacks a 26–45 age group. Digital techniques seemed to offer a more exact analysis, but returned similar results to studies performed over 40 years ago, therefore offering important information on evolutionary tendencies. Conclusions: Increase in glial tissue, calcifications, and glial cysts have a defining role as age-related changes in the pineal gland.

Human cerebral organoids (hCOs) offer the possibility of deepening the knowledge of human brain development, as well as the pathologies that affect it. The method developed here describes the efficient generation of hCOs by going directly from two-dimensional (2D) pluripotent stem cell (PSC) cultures to three-dimensional (3D) neuroepithelial tissue, avoiding dissociation and aggregation steps. This has been achieved by subjecting 2D cultures, from the beginning of the neural induction step, to dual-SMAD inhibition in combination with CHIR99021. This is a simple and reproducible protocol in which the hCOs generated develop properly presenting proliferative ventricular zones (VZs) formed by neural precursor and radial glia (RG) that differentiate to give rise to mature neurons and glial cells. The hCOs present additional cell types such as oligodendrocyte precursors, astrocytes, microglia-like cells, and endothelial-like cells. This new approach could help to overcome some of the existing limitations in the field of organoid biotechnology, facilitating its execution in any laboratory setting.

Given the scarcity of research on hyperbole and simile in Cognitive Linguistics, it is important to explore these figures of speech, whose interaction has only been tangentially addressed in this field. Thus, the main aim of the study is to provide a detailed description of hyperbolic like comparison constructions by examining the structural and conceptual diversity of the source and target domains, as well as the characteristics of the third component of hyperbolic similes, namely the elaboration. With this objective in mind, we carried out an analysis of 120 examples of hyperbolic similes retrieved from the comedy sitcom Friends (1994-2004). Our findings show that the source domains of hyperbolic like comparison constructions are both structurally and conceptually more complex than the target domains.

This paper provides evidence of the fruitfulness of combining analytical categories from Cognitive Linguistics and Critical Discourse Analysis for the analysis of complex literary characterizations. It does so through a detailed study of the “tributes”, i.e. the randomly selected children who have to fight to death in a nationally televised show, in The Hunger Games. The study proves the effectiveness of such categories to provide an analytically accurate picture of the dystopian world depicted in the novel, which is revealed to include a paradoxical element of hope. The type of dehumanization that characterizes the dystopian society of Panem is portrayed through an internally consistent set of ontological metaphors which project negative aspects of lower forms of existence onto people. This selection of metaphors promotes a biased perspective on the poor inhabitants of Panem, while legitimizing the social inequalities the wealthy Capitol works hard to immortalize. However, Katniss undergoes a metamorphosis through her discovery of her own identity, which hints at an emerging female empowerment. This transformation, together with her identification with the Mockingjay, a supernatural being that voices her beliefs and emotions, contributes to disrupting the status quo imposed by the almighty Gamemakers and to purveying a message of optimism.

The present study focuses on the frequency of phrasal verbs with the particle up in the context of crime and police investigative work. This research emerges from the need to enlarge McCarthy and O’Dell’s (2004) scope from purely criminal behavior to police investigative actions. To do so, we relied on a corpus of 504,124 running words made up of spoken dialogues extracted from the script of the American TV series Castle shown on ABC since 2009. Based on Rudzka-Ostyn’s (2003) cognitive motivations for the particle up, we have identified five different meaning extensions for our phrasal verbs. Drawing from these findings, we have designed pedagogical activities for those L2 learners that study English at the Police Academy.

One of the characteristics of autism spectrum disorder (ASD) subjects is postural control deficit, which is significant when somatosensory perception is affected. This study analyzed postural stability evolution after physical therapy exercises based on balance training. The study included 28 children with ASD (average age 8 years, average weight 32.18 kg). The rehabilitation program involved performing balance exercises twice a week for three months. Subject assessment was carried out using the RSScan platform. The parameters were the surface of the confidence ellipse (A) and the length of the curve (L) described by the pressure center, which were evaluated before and after the rehabilitation program. Following data processing, we observed a significant decrease in the surface of the confidence ellipse by 92% from EV1 to EV2. Additionally, a decrease of 42% in the curve length was observed from EV1 to EV2. A t test applied to the ellipse surface showed a p = 0.021 and a Cohen’s coefficient of 0.8 (very large effect size). A t test applied to the length L showed p = 0.029 and Cohen’s coefficient of 1.27 mm. Thus, the results show a significant improvement in the two parameters. The application of the program based on physical exercise led to an improvement in the balance of children with autism under complex evaluation conditions.

Background/Objectives: Ischemic sudden cardiac death (SCD) is a devastating event that often occurs in apparently healthy individuals. Genetic susceptibility may play a key role in the pathogenesis of such ischemic events. This study aimed to investigate the correlations between Human Leukocyte Antigen (HLA) alleles, genotypes, and haplotypes and SCD to identify potential risk factors. This study also investigated three Single-Nucleotide Polymorphisms (SNPs) in the MYBPC3 gene and their association with SCD. Methods: We conducted an exploratory study between 2022 and 2024 in North-Western Transylvania (Romania) on 81 autopsy-confirmed SCD cases, compared with 162 controls for HLA typing, and with 96 controls for SNPs. HLA analysis of the HLA-DRB1 and HLA-DQB1 genes was performed using low-resolution SSP-PCR. The three SNPs in the MYBPC3 gene: rs142317339 (C > T), rs148808089 (G > A), and rs11570076 (G > A) were performed using a Real-Time PCR System. Results: The HLA-DRB1*07 allele has reduced odds of SCD, after adjustment for age and sex, and the HLA-DRB1*08 allele showed a trend toward increased odds. No statistically significant associations were detected at the allele or genotype level for HLA-DQB1. Haplotype-based analyses further revealed that genetic susceptibility is driven predominantly by low-frequency protective haplotypes rather than by common risk haplotypes, with several combinations conferring strong or moderate protection (HLA-DRB1*07~HLA-DQB1*03, HLA-DRB1*07~HLA-DQB1*02, and HLA-DRB1*15~HLA-DQB1*05). No statistically significant association was found between the three SNPs studied in the two groups, and their frequencies were very low. Conclusions: Specific HLA-DRB1 and HLA-DQB1 alleles and haplotypes may be associated with protection against SCD, supporting a possible immunogenetic role in SCD and the identification of genetic risk markers.