Search Results (783)

The accurate classification of pancreatic cystic lesions remains clinically challenging due to overlapping imaging features and variable malignant potential. Mucinous cystic neoplasms, in particular, require early identification given their premalignant nature. RNA profiling presents a promising alternative to current diagnostic limitations—a molecular lens sharpened by AI-driven pattern recognition. This study aimed to evaluate the diagnostic potential of RNA signatures for differentiating pancreatic cyst subtypes and to clarify their roles in their pathophysiology. The study included 31 patients with pancreatic lesions who underwent endoscopic ultrasound-guided fine-needle aspiration. RNA was extracted from cyst fluid, tissue, and peripheral blood. Expression of 17 target genes was analyzed using qPCR. Gene expression patterns were compared across mucinous cystic neoplasms, serous cystic neoplasms, pseudocysts, adenocarcinoma, and chronic pancreatitis cohorts. Diagnostic accuracy was evaluated via ROC analysis. Mucinous cysts exhibited significant overexpression of MUC1, ITGA2, ELOVL6, and MUC5AC genes compared to serous cysts and pseudocysts. PKM gene expression correlated with increasing malignant potential. In blood plasma, only MUC1, MUC4, and PYGL were elevated in adenocarcinoma compared to mucinous neoplasms. We identified a distinct RNA signature that can distinguish mucinous cystic neoplasms from benign cystic lesions (serous cysts and pseudocysts), which could be useful for guiding patient management and improving clinical outcomes. Validation in broader cohorts is essential for clinical implementation. Full article

Endometrial carcinoma (EC) is the most common malignancy of the female reproductive tract, with increasing incidence driven by aging populations and obesity. While molecular classification has improved diagnostic precision, the identification of clinically relevant metabolic biomarkers remains incomplete, and targeted therapies are not yet standardized. In this study, we investigated metabolic alterations in four EC cell lines (AN3-CA, EFE-184, HEC-1B and MFE-296) compared to non-malignant controls under normoxic and stress conditions (hypoxia and lactic acidosis) to identify metabolomic differences with potential clinical relevance. Untargeted gas chromatography–mass spectrometry (GC/MS) and targeted liquid chromatography–mass spectrometry (LC/MS) profiling revealed two distinct metabolic subtypes of EC. Cells of metabolic subtype 1 (AN3-CA and EFE-184) exhibited high biosynthetic and energy demands, enhanced cholesterol and hexosyl-ceramides synthesis and increased RNA stability, consistent with classical cancer-associated metabolic reprogramming. Cells of metabolic subtype 2 (HEC-1B and MFE-296) displayed a phospholipid-dominant metabolic profile and greater hypoxia tolerance, suggesting enhanced tumor aggressiveness and metastatic potential. Key metabolic findings were validated via real-time quantitative PCR. This study identifies and characterizes distinct metabolic subtypes of EC within the investigated cancer cell lines, thereby contributing to a better understanding of tumor heterogeneity. The results provide a basis for potential diagnostic differentiation based on specific metabolic profiles and may support the identification of novel therapeutic targets. Further validation in three-dimensional culture models and ultimately patient-derived samples is required to assess clinical relevance and integration with current molecular classifications. Full article

Acanthamoeba is a widespread free-living amoeba known as an opportunistic parasite of humans and other animals. It comprises several species, whose characterisation relies currently on the analysis of 18S rDNA sequences, recognising more than twenty genotypes; however, the distinction between closely related lineages remains unclear. In this study, the spacer region between the mitochondrial large and small subunits of rRNA genes was analysed for its usefulness as a marker for molecular typing. Previous studies have shown that the mitochondrial spacer contains a group of five transfer RNA (tRNA) genes, and that its length and sequence vary considerably between strains. A total of forty-two mitochondrial spacers were examined here, including twenty-five newly recovered sequences, from ten genotypes covering the three morphological groups of Acanthamoeba. The results showed that lineage-specific profiles can be defined for morphological groups 2 and 3 species (MG2 and MG3), with phylogenetic analysis consistent with that of rDNA, allowing for strain identification at the subtype level. In addition, morphological group 1 (MG1) species have a different tRNA gene arrangement distinguishing them from the others. Mitochondrial spacers therefore appear to be promising phylogenetic markers for the molecular typing of Acanthamoeba. Full article

This review covers issues related to the characteristics, diagnosis, and treatment of colorectal cancer (CRC). It discusses traditional methods of treating colorectal cancer, including surgery, chemotherapy, and radiotherapy, as well as modern approaches, including targeted therapies, immunotherapy, and innovative gene therapy strategies. Particular attention is paid to the identification of molecular subtypes of CRC, which has revolutionized treatment in advanced stages of the disease and contributed to improved patient survival. The role of biomarkers, including liquid biopsy, in diagnosis, therapy monitoring, and treatment response assessment is emphasized. The potential of artificial intelligence in planning and optimizing surgical procedures is also discussed, opening up new possibilities in personalized therapy. This article provides up-to-date knowledge on the molecular mechanisms of CRC, diagnostic prospects, and directions for the development of precision therapies, serving as a valuable source of information for both clinicians involved in the treatment of CRC and patients wishing to deepen their knowledge of the disease and modern therapeutic options. Full article

Diverse neuronal nicotinic acetylcholine receptor (nAChR) subtypes are expressed in hippocampal interneurons. Single-cell analysis of mRNA expression previously revealed prominent co-expression of the α3 and β2 subunits within rat interneurons in the CA1 region. Although the α3 subunit (traditionally expressed together with β4) is usually associated with the peripheral nervous system, its significant co-expression with the β2 subunit in hippocampal interneurons suggests a distinct, potentially novel central nervous system nAChR subtype. We demonstrate that the human α3 and β2 subunits injected into Xenopus laevis oocytes can assemble into at least two functionally distinct subtypes of nAChRs based on different subunit stoichiometries. These subtypes exhibit similar reversal potentials but differ significantly in their desensitization kinetics and acetylcholine (ACh) affinities. The response obtained from a 1:5 α3:β2 mRNA injection ratio shows a higher affinity for ACh and significantly greater desensitization during prolonged ACh application compared to the response obtained from a 5:1 α3:β2 mRNA injection ratio. The identification of distinct functional α3β2 subtypes, characterized by differential desensitization kinetics and ACh affinity, could represent novel targets for the potential development of highly selective cognitive therapeutics for conditions such as Alzheimer’s disease, autism spectrum disorder, and attention deficit hyperactivity disorder, where hippocampal nAChRs are implicated. Full article

Duck viral enteritis (DVE) is an acute and highly contagious disease that affects waterfowl such as ducks, geese and swans. Duck enteritis virus (DEV) is the pathogen, causing huge economic losses to waterfowl farming in recent years. Establishing a rapid, simple, and visual detection should facilitate the early identification of DEV. After the amplification primers and reaction conditions were optimized, three multienzyme isothermal rapid amplification (MIRA) methods—basic MIRA, MIRA–quantitative PCR (MIRA–qPCR) and MIRA–lateral flow dipstick (MIRA–LFD)—were established to detect DEV. Specificity analyses showed that the three MIRA methods specifically detected DEV, with no cross-reaction with fowl adenovirus serotype 4, novel goose astrovirus, Muscovy duck reovirus, avian influenza virus subtype H9, or duck circovirus. The basic MIRA reaction was completed in 30 min at 35 °C, requiring only a pair of primers. Detection with MIRA–qPCR or MIRA–LFD was completed within 20 min, and the limits of detection were 1 × 10¹ copies/μL for both. MIRA–LFD required no specialized instruments, and the results could be viewed directly with the naked eye. Compared with the traditional PCR, MIRA assays are simple, rapid, and effective and therefore more suitable for the field detection of DEV. Full article

This paper presents a comprehensive methodology for assessing the resilience of landscapes to human impact in western Kazakhstan. The approach developed is based on integrating remote sensing data (MODIS, SMAP, NDVI and NDSI), the results of field surveys, and multi-criteria analysis methods in a GIS environment. The assessment covered over 50 landscape types and subtypes using ten key indicators reflecting climatic, geomorphological, soil, hydrological, and biotic characteristics. These indicators were normalised, aggregated and summarised to create an integral index of landscape resilience, which allowed four resilience classes to be identified, ranging from highly vulnerable to relatively resilient. The spatial analysis revealed that over 60% of the region’s territory is classified as high-vulnerability, predominantly within semi-desert and desert zones, which are vulnerable to climatic risks, degradation of vegetation cover and human activity. Verification of the results based on remote monitoring data for the period 2000–2024 and field observations confirmed the reliability of the developed methodology. The results obtained allow the identification of areas prioritised for environmental monitoring, restoration and sustainable land use in arid climate conditions. A plan of measures for regulation and restoration of ecosystems and spatial planning tools are proposed. The obtained data can be used for the development of regional environmental policy and sustainable land use strategies. Full article

Background: Older adults who are hospitalized in internal medicine wards often present with a challenging interplay of multimorbidity and geriatric syndromes. The timely identification of clinical and geriatric predictors of in-hospital mortality is crucial for guiding individualized care pathways and ensure appropriate resource allocation. In this study, we investigate the prognostic impact of frailty, delirium—including its motor subtypes—and global comorbidity burden on in-hospital mortality in patients aged 70 years and older. Methods: We conducted a retrospective observational study including 556 consecutive patients aged ≥ 70 years who were admitted to the Internal Medicine Unit of the University Hospital of Parma from January 2019 to July 2019. Demographic, clinical, and geriatric data were collected within 48 h of admission, including Clinical Frailty Scale (CFS), Cumulative Illness Rating Scale (CIRS), and delirium diagnosis with the 4AT tool. Multivariate Cox and logistic regression analyses were performed, including sex-stratified models. Results: The median age was 85 years (IQR 80–89), 58% were female, and in-hospital mortality was 11% (n = 61). Non-survivors had higher rates of severe frailty (CFS ≥ 7: 39% vs. 16%, p < 0.001), prevalent delirium (20% vs. 4%, p < 0.001), hypokinetic delirium (20% vs. 5%, p < 0.001), liver disease (23% vs. 11%, p = 0.008), cancer (44% vs. 24%, p < 0.001), and dementia (43% vs. 29%, p = 0.026) and a higher CIRS severity index (≥3:55% vs. 31%, p < 0.001). In Cox regression, independent predictors of death were prevalent delirium (HR 4.66, 95% CI 2.42–8.96), CFS ≥ 7 (HR 2.26, 95% CI 1.32–3.87), CIRS-LIVER ≥ 2 (HR 2.05, 95% CI 1.18–3.56), and cancer (HR 1.83, 95% CI 1.07–3.14). Sex-stratified models showed that in males, prevalent delirium (HR 10.23) and cancer (HR 2.49) predicted mortality, whereas in females, hypokinetic delirium (HR 3.67) and CIRS-LIVER ≥ 2 (HR 2.75) were the strongest predictors. Logistic regression confirmed these associations and additionally identified anemia and CFS ≥ 7 in males and CIRS severity index ≥ 3 in females as significant risk factors. Conclusions: In elderly patients who are admitted to internal medicine wards, prevalent and hypokinetic delirium, severe frailty, and high comorbidity burden, particularly liver disease and cancer, are strong independent predictors of in-hospital mortality, with distinct sex-specific patterns. Early multidimensional geriatric assessment may improve risk stratification and guide targeted interventions. Full article

For ten years, DNA methylation appeared as a major step in the understanding and issues of prostate cancers. Indeed, although classical biochemical parameters are still useful for prostate cancer diagnosis, they have poor sensitivity and are not specific for prostate cancer subtypes. The recent boom in the identification of specific DNA methylation profiles and the rapid development of liquid biopsies have completely modified the care of patients and may greatly influence outcomes in the future. Indeed, DNA methylation modifications could substantially improve the diagnosis by identifying specific prostate subtypes, improve follow-up to monitor residual disease, improve therapeutic efficiency by predicting the response to treatment, and improve the health quality of patients since these epigenetic modifications can easily be detected in non-invasive liquid biopsies. Full article

Various types of sensilla are densely distributed on the antennal surfaces of insects. The specialization of perception and ecological adaptability of antennae in detecting external environmental signals are reflected in the morphology, function, number, and distribution pattern of sensilla. L. invasa, O. bipolaris, and O. maskelli are three types of wasps that harm eucalyptus trees. To investigate the perception and reception methods of chemical signals from eucalyptus trees by the three gall wasps and compare interspecific differences, the antennal morphology and sensillar characteristics of these three gall wasps were systematically analyzed using scanning electron microscopy, including sensillar length, type, distribution, and number. Knee-shaped antennae, comprising the radicle, scape, pedicel, anelli, funicle, and club, are present in all three species. However, significant interspecific differences were observed in total antennal length and funicular number. Five major sensilla categories, comprising nine subtypes, were identified. Among these, five types (BS, CH, CS, TSI, TSII) were common to all three gall wasp species. PSI and PSII were unique to L. invasa, while O. bipolaris and O. maskell shared PSIII. Compared to O. maskelli, O. bipolaris possessed a significantly greater number of PSIII sensilla, which were also longer. TSIII was found exclusively in O. bipolaris. Interspecific differences were evident in antennal morphology, as well as in the number, size, and distribution of the sensilla. These variations in sensilla and antennal shape serve as a morphological foundation for species identification in addition to reflecting ecological adaptation and functional differentiation in environmental signal perception. Full article

Background and Objectives: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder often associated with metabolic disturbances such as insulin resistance and metabolic syndrome (MetS). Visceral adiposity index (VAI) is a validated marker that reflects visceral fat distribution and cardiometabolic risk. This study aimed to compare VAI levels among different PCOS phenotypes to evaluate cardiometabolic risk across these phenotypes. Materials and Methods: This prospective case–control study included 180 PCOS patients and 51 healthy controls without any metabolic or reproductive issues. Patients were divided into the following subtypes based on the Rotterdam criteria: Phenotype A (n = 96), clinical and/or biochemical hyperandrogenism (HA) + oligo-anovulation (OA) + polycystic ovarian morphology (PCOM); Phenotype B (n = 19), HA + OA; Phenotype C (n = 35), HA + PCOM; and Phenotype D (n = 30), OA + PCOM. VAI was calculated for women using anthropometric and biochemical parameters. Results: In the total PCOS group, VAI levels were significantly higher than in controls (p < 0.001). Phenotypes A and B had higher VAI values than controls and also higher in Phenotype A than in Phenotypes C and D (p = 0.003 and p = 0.001, respectively). While present in 38 patients (21.10%) in the PCOS group, there was no metabolic syndrome (MetS) in controls (p < 0.001). In Phenotypes A, B, and D, while more patients had MetS than controls (p < 0.001, 0.004, and 0.021, respectively), more patients had MetS in Phenotype A compared to Phenotypes C and D (p = 0.003 and p = 0.021, respectively). Given ROC analysis, the VAI cut-off value in predicting MetS in the PCOS group was 1.66 (sensitivity = 94.74% and specificity = 83.10%). Conclusions: PCOS phenotypes characterized by HA and OA, particularly Phenotypes A and B, are associated with higher VAI values and an increased frequency of MetS risk. Early identification of these phenotypes may facilitate the implementation of targeted metabolic risk reduction and early intervention strategies, thereby contributing to the reduction of cardiovascular risk. Full article

Introduction: Increasingly, identification of BRAF mutation in colorectal cancer is used to guide management and predict cancer behaviour. There is, however, still significant diversity within this cohort of patients, both in terms of clinical phenotype and treatment outcomes. This may be explained, at least in part, by differences between classes of BRAF mutations and the presence of concomitant mutations. Methods: We present a retrospective cohort study of sequential patients diagnosed with BRAF-mutated (V600 and non-V600) colorectal cancer between 2014 and 2022. Information regarding presentation, treatment outcomes and molecular subtype was identified using the electronic medical record. Results: This study included 406 patients with BRAF-mutated colorectal cancer, 253 (228 ^V600BRAF) of whom had localised disease and 153 (137 ^V600BRAF) with metastatic disease at the time of diagnosis. In patients with localised disease at diagnosis, the ^V600BRAF mutation was associated with older median age (73 vs. 63 years, p = 0.04) and a higher prevalence of right-sided primary (73% vs. 40%, p < 0.01), mismatch repair deficiency (56% vs. 8%, p < 0.01), and faster time to disease relapse (p = 0.006). In the metastatic setting, ^non-V600BRAF mutation was associated with a higher prevalence of KRAS mutation (27% vs. 1%, p < 0.01), NRAS mutation (14% vs. 3%, p = 0.04) and PIK3CA mutation (33% vs. 8%, p = 0.02). Mismatch repair deficiency was more common in patients with ^V600BRAF mutations than in those with ^non-V600BRAF mutations (20% vs. 0%, p = 0.01). The median survival of patients with the ^V600BRAF mutation was 14 months, and 34 months in those with ^non-V600BRAF mutations. Concomitant RNF43 mutation in metastatic disease, was associated with a significantly higher incidence of disease control from combined BRAF and EGFR inhibition, when compared to those without an RNF43 mutation (100% vs. 54%, p = 0.02). Conclusions: Presentation and outcomes of BRAF-mutated colorectal cancer are heterogenous. The type of BRAF mutation, and the presence of concomitant RNF43 mutation, may explain some of the differences in cancer behaviour. Routine reporting of RNF43 mutations would assist clinicians to give more personalised treatment recommendations. Full article

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer (BC), comprising approximately 20% of newly diagnosed BC cases. The poor prognosis, high recurrence rates, and inefficacy of hormone-based therapies make TNBC one of the greatest challenges in contemporary oncology. The unique immunological features of TNBC, including relatively high tumor mutational burden, abundance of tumor-infiltrating lymphocytes, and elevated PD-L1 expression, offer a wide range of opportunities for immunotherapeutic approaches, of which the most progressive and promising are neoantigen-driven ones. This review examines the current landscape of neoantigen-based therapeutic approaches in TNBC treatment, spanning from discovery methodologies to clinical applications. We provide a critical analysis of the tumor microenvironment (TME) in TNBC, highlighting the balance between its immunoactivating (CD8+ T-cells, dendritic cells) and immunosuppressive (regulatory T-cells, M2 macrophages) components as the key determinant of therapeutic success, as well as reviewing the emerging approaches to TME reprogramming and recruiting in favor of better outcomes. We also present state-of the-art methods in neoantigen identification and prioritization, covering the landscape of technological platforms and prediction algorithms, addressing the existing accuracy limitations along with emerging computational solutions, and comprehensively discussing the TNBC neoantigen spectrum. Our analysis shows the strong domination of patient-specific (“private”) neoantigens over shared variants in the TNBC, with TP53 as the only gene with recurrent variants. Finally, we extensively cover neoantigen-recruiting therapeutic modalities including adoptive cell therapies, personalized vaccine platforms (peptide-based, mRNA/DNA vaccines, dendritic cell vaccines), and oncolytic viruses-based approaches. Our study of current clinical trials demonstrates the substantial gap between early proof-of-concept experiments and further applicability of neoantigen-driven therapies. The major challenges hampering the success of such methods include neoantigen prediction inaccuracy rates, high manufacturing costs, and time consumption. Promising ways to overcome these difficulties include the development of combinational strategies, TME modeling and modifying, and improvement of the therapy delivery properties, along with the optimization of production workflows and cost-effectiveness of vaccine development. Full article

Background: Soft tissue sarcomas (STSs) histopathological classification system and the clinical and molecular-based tools that are currently employed to estimate its prognosis have several limitations, impacting prognostication and treatment. Clinically driven molecular profiling studies may cover these gaps and offer alternative tools with superior prognostication capability and enhanced precision and personalized treatment approaches identification ability. Materials and Methods/Results: We performed DNA sequencing (DNA-seq) and RNA sequencing (RNA-seq) to portray the molecular profile of 102 samples of high-grade STS, comprising the three most common STS histotypes. The analysis of RNA-seq data using unsupervised machine learning models revealed previously unknown molecular patterns, identifying four transcriptomic subtypes/clusters (TCs). This TC-based classification has a clear prognostic value (in terms of overall survival (OS) and disease-free survival (DFS)), a finding that was externally validated using independent patient cohorts. The prognostic value of this TC-based classification outperforms the prognostic accuracy of clinical-based (SARCULATOR nomograms) and molecular-based (CINSARC) prognostication tools, being one of the first molecular-based classifications capable of predicting OS in STS. The analysis of DNA-seq data from the same cohort revealed numerous and, in some cases, never documented molecular targets for precision treatment across different transcriptomic subtypes. The functional and predictive value of each genomic variant was analyzed using the Molecular Tumor Board Portal. Conclusions: This newly identified TC-based classification offers a superior prognostic value when compared with current gold-standard clinical and molecular-based prognostication tools, and identifies novel molecular targets for precision treatment, representing a cutting-edge tool for predicting prognosis and guiding treatment across different stages of STS. Full article

Background: Problematic Internet gaming (PIG), considered an early stage of Internet gaming addiction (IGA), has become increasingly prevalent among adolescents. This study focused on deviant peer affiliation (DPA) and hedonic gaming experience (HGE) as key mediators and examined four psychosocial risk factors closely related to them: interpersonal incompetence (II), perceived stress (PS), frustration (FR), and emotional loneliness (EL). Specifically, the study investigated how these four psychosocial risk factors influence adolescents’ DPA, HGE, and PIG, and whether DPA and HGE mediate these relationships. Methods: Based on existing validated scales, we developed a questionnaire to measure these seven constructs (II, PS, FR, IC, DPA, HGE, and PIG), proposed 14 hypotheses, and collected 214 valid responses from adolescents. Structural equation modeling (SEM) was used to test the hypothesized model. Findings: The results showed that all 14 hypotheses were supported. Specifically, interpersonal incompetence significantly predicted perceived stress; stress led to frustration; and frustration, in turn, contributed to emotional loneliness. Furthermore, all four psychosocial risk factors significantly predicted deviant peer affiliation, hedonic gaming experience, and ultimately, problematic Internet gaming among adolescents. Both DPA and HGE mediated the effects of psychosocial risk factors on adolescent problematic Internet gaming (PIG), with the model explaining moderate-to-high variance. This study highlights the importance of segmenting adolescents into more specific subgroups based on the distinct developmental pathways leading to PIG. Implications: Understanding the step-by-step mechanisms and psychological drivers of different adolescent subtypes can provide a more solid foundation for early identification and targeted intervention efforts. Full article