Background Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease that is classified based on the presence of nasal polyps. However, whether CRS and nasal polyps represent discrete entities or a continuous progression remains unclear. Most studies have relied on cross-sectional comparisons, which limit insight into its pathophysiology. This study aimed to test whether CRS subtypes lie on a continuous trajectory by applying pseudotime ordering to CRS transcriptomic data. Methods Gene expression data were obtained from the Gene Expression Omnibus (GSE36830), which consists of control, chronic rhinosinusitis without nasal polyps (CRSsNP), uncinate tissue (CRSwNP UT), and nasal polyp tissue (CRSwNP NP) from chronic rhinosinusitis with nasal polyps. Pathway activity was quantified using Gene Set Variation Analysis (GSVA) based on gene sets for immune, inflammatory, and epithelial pathways. Highly variable pathways were selected and used as input to reconstruct a pseudotemporal disease trajectory. Statistical associations were assessed using Spearman correlation and the Jonckheere–Terpstra trend test. Results Pseudotime reconstruction showed an ordered molecular trajectory extending from control samples through CRSsNP and CRSwNP UT, with nasal polyp samples forming a distinct end stage. Pseudotime showed a strong monotonic association with disease stage (Spearman's ρ=0.743, p<0.001), indicating an ordered progression of molecular changes across disease states. Progressive disease was characterized by increasing activation of immune pathways, including hypersensitivity, alongside declining activity of epithelial stress response and metabolic pathways. Conclusion These findings demonstrate that CRS represents a continuous molecular disease spectrum. Nasal polyposis emerges as a distinct molecular end state characterized by dominant immune activation. This pseudotime-based framework provides insight into CRS pathogenesis and provides evidence for specific therapeutic strategies.
Background Down syndrome (DS) is a genetic disorder caused by addition of a full or partial chromosome 21. The most common type of DS (90–95%) is pure trisomy 21; mosaicism occurs in 6–7%, and about 3–5% comprises translocation DS including Robertsonian translocation, which could be inherited from parents. This case shows a Robertsonian translocation der(21;21)(q10:q10) DS and the common financial problem among Indonesian parents being their inability to pay for examinations to determine the origin of the abnormality (inherited or de novo), which is a big challenge for genetic counselors. Case Description A 2-month-old baby boy was admitted to the hospital with suspect Down syndrome referred by a pediatrician. The patient was the only child of 25-year-old parents. Physical examination showed several characteristics of DS, including upslanting palpebral fissure, a flat nasal bridge, horizontal palmar creases, sandal gap, and continuous murmur in upper left sternal border due to patent ductus arteriosus. Cytogenetic testing revealed the karyotype of derivative chromosome 21, namely Robertsonian translocation 46,XY,+21,der(21;21)(q10:q10). Parents declined to order cytogenetic testing due to financial concerns. Conclusion Parents’ karyotype is critical to confirm the origin of the translocation. It is important to calculate the recurrence risk correctly especially when parents still want another child and to do non-directive counseling in terms of reproductive options. However, it cannot be done in this case because of the lack of parent’s karyotypes. Genetic counseling plays an essential role in providing an accurate recurrence risk based on the type of trisomy for future offspring and reproductive planning.
Macrophages in the tumor microenvironment are involved in promoting cancer growth and enabling it to evade therapies. By acting as something like a tumor's "underground," these cells dampen down the "calls for help" that chemotherapy or radiotherapy might otherwise trigger. They also appear to enable some cells in the cancers to reset themselves into cancer stem cells (CSCs), allowing them to divide and differentiate. Cancer stem cells are compelled to initiate tumors and maintain their growth. In part, the tumor-associated macrophages (TAMs) effect this by secreting cytokines with well-established roles in regulating stemness, as well as proteins that govern cell migration and are known to help keep CSCs in the niche where the tumor formed and maintain the tumor. Prognostic studies have found that TAMs are associated with worse patient outcomes. This article reviews the existing knowledge on TAMs in supporting the survival and maintenance of CSCs, increasing tumor resilience and resistance to therapy. We did a systematic review using the keywords CSC, TAM, tumor microenvironment (TME), and extracellular matrix remodeling from the following databases: ScienceDirect, PubMed, NCBI, Nature, Google Scholar, and Oxford Academic for articles published between 2010 to 2026. The underlying premise of the current investigation is that macrophages facilitate the maintenance of the "stemness" characteristics of CSCs. The TAM-CSC alliance must be interrupted to improve therapeutic outcomes and reduce tumor recurrence. Our review focuses on addressing the difficulties presented by CSCs and TME through advanced research techniques and specific combination treatments. This alternative method offers a less harsh and more effective therapy that will improve the patient’s outcomes by effectively eradicating tumor cells and modifying the tumor microenvironment to enhance the immune system's capability to combat the tumor.
Early-onset colorectal cancer (EOCRC) is increasingly recognized as a global public health concern. Biomarker research in EOCRC has expanded across hereditary, molecular, epigenetic, liquid biopsy, microbiome, and multi-omics domains, but the overall research landscape remains fragmented. This study aimed to map global research trends and identify prominent and underdeveloped topics in EOCRC biomarker research. A bibliometric analysis was conducted using publications on EOCRC biomarkers retrieved on October 27, 2024. Eligible documents were limited to English-language articles, reviews, and conference proceedings, with a final publication stage and no restriction on publication year. After screening, 134 relevant documents published between 1985 and 2024 were included. Bibliometric indicators, including publication trends, leading contributors, influential publications, topic evolution, and keyword co-occurrence patterns, were analyzed using Biblioshiny (Bibliometrix R package v4.1.3) and VOS viewer (v1.6.18). Early-onset colorectal cancer biomarker research showed steady growth, with an annual growth rate of 7.54% and a publication peak in 2023. The dataset included 134 documents from 92 sources and involved 1,121 authors, with international collaboration observed in 20.9% of publications. Earlier studies focused mainly on hereditary predisposition, Lynch syndrome, mismatch repair genes, and microsatellite instability. More recent research shifted toward molecular profiling, epigenetic alterations, liquid biopsy, gut microbiota, tumor microenvironment, and multi-omics approaches. Underdeveloped areas included diagnostic biomarker validation, screening implementation, gut microbiota, risk factors, and machine learning-based biomarker discovery. Overall, EOCRC biomarker research has evolved from a hereditary-centered focus toward a broader precision oncology framework, but further work is needed to strengthen validation, translational relevance, and clinical applicability across diverse populations.
Background Globally, violent deaths represent a serious public health issue, and Mexico has shown an increase in homicides. Exposure to violence has been linked to adverse mental and physical health outcomes, including cardiovascular disease. However, population-level evidence linking homicide mortality to myocardial infarction (MI) mortality remains limited. This study assesses the association between homicides and mortality from myocardial infarction in Mexico from 2000 to 2019. Methods This ecological time-series study used national mortality data from the Mexican National Institute of Statistics and Geography (INEGI). Adjusted annual mortality rates were calculated. Mortality trends were evaluated using Joinpoint software. The association between homicides and other causes of mortality was analyzed using Pearson correlation and univariate and multivariate regression analyses. Results During the study period, the average adjusted mortality rates were 16.8/100,000 for homicides and 67.4/100,000 for myocardial infarction. Both homicide and MI mortality rates increased significantly over time. In simple linear regression, homicides only showed significant associations with myocardial infarction (B=0.55, p<0.05). In multivariate regression analyses, homicide mortality remained significantly associated with MI mortality after adjustment for unemployment, gross domestic product per capita (GDP-PC), and diabetes mortality, although the association was attenuated when suicide mortality was included in the model. Conclusion At the population level, from 2000 to 2019 both homicide and MI mortality rates increased significantly, while homicides were positively associated with myocardial infarction mortality in Mexico. Elevated homicide rates act as a population-level stressor that coincides with higher mortality from heart attacks.
