Geometric characteristics of stromal collagen fibres in breast cancer using differential interference contrast microscopy.

Breast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label-free imaging technique well suited to visualise weak optical phase objects such as cells and tissue. This study aims to compare stromal collagen fibre characteristics between in situ and invasive breast tumours using DIC microscopy and investigate the prognostic value of collagen parameters in BC. A tissue microarray was generated from 200 cases, comprising ductal carcinoma in situ (DCIS; n = 100) and invasive tumours (n = 100) with an extra 50 (25 invasive BC and 25 DCIS) cases for validation was utilised. Two sections per case were used: one stained with haematoxylin and eosin (H&E) stain for histological review and one unstained for examination using DIC microscopy. Collagen fibre parameters including orientation angle, fibre alignment, fibre density, fibre width, fibre length and fibre straightness were measured. Collagen fibre density was higher in the stroma of invasive BC (161.68 ± 11.2 fibre/µm2) compared to DCIS (p < 0.0001). The collagen fibres were thinner (13.78 ± 1.08 µm), straighter (0.96 ± 0.006, on a scale of 0-1), more disorganised (95.07° ± 11.39°) and less aligned (0.20 ± 0.09, on a 0-1 scale) in the invasive BC compared to DCIS (all p < 0.0001). A model considering these features was developed that could distinguish between DCIS and invasive tumours with 94% accuracy. There were strong correlations between fibre characteristics and clinicopathological parameters in both groups. A statistically significant association between fibre characteristics and patients' outcomes (breast cancer specific survival, and recurrence free survival) was observed in the invasive group but not in DCIS. Although invasive BC and DCIS were both associated with stromal reaction, the structural features of collagen fibres were significantly different in the two disease stages. Analysis of the stroma fibre characteristics in the preoperative core biopsy specimen may help to differentiate pure DCIS from those associated with invasion.

Portable noninvasive technologies for early breast cancer detection: A systematic review.

Breast cancer remains a leading cause of cancer mortality worldwide, with early detection crucial for improving outcomes. This systematic review evaluates recent advances in portable non-invasive technologies for early breast cancer detection, assessing their methods, performance, and potential for clinical implementation. A comprehensive literature search was conducted across major databases for relevant studies published between 2015 and 2024. Data on technology types, detection methods, and diagnostic performance were extracted and synthesized from 41 included studies. The review examined microwave imaging, electrical impedance tomography (EIT), thermography, bioimpedance spectroscopy (BIS), and pressure sensing technologies. Microwave imaging and EIT showed the most promise, with some studies reporting sensitivities and specificities over 90 %. However, most technologies are still in early stages of development with limited large-scale clinical validation. These innovations could complement existing gold standards, potentially improving screening rates and outcomes, especially in underserved populations, whiles decreasing screening waiting times in developed countries. Further research is therefore needed to validate their clinical efficacy, address implementation challenges, and assess their impact on patient outcomes before widespread adoption can be recommended.

Association between sedentary behavior and wish to die among adults aged ≥50 years: Findings from the Irish Longitudinal Study on Ageing.

We investigated the association between sedentary behavior (SB) and wish to die (WTD; i.e., feeling that one would be better off dead or wishing for one's own death), and the extent to which this can be explained by sleep problems, depression, anxiety, loneliness, perceived stress, and social network in a nationally representative sample of adults aged ≥50 years from Ireland. Cross-sectional data from Wave 1 of the Irish Longitudinal Study on Ageing 2009-2011 were analyzed. WTD was defined as answering affirmatively to the question "In the last month, have you felt that you would rather be dead?" SB was used as a continuous variable (hours/day), and also as a categorical (< or ≥8 h/day) variable. Multivariable logistic regression and mediation analyses were conducted. Data on 8163 adults aged ≥50 years were analyzed [mean (SD) age 63.6 (9.1) years; 48.0% males]. Overall, ≥8 (vs. <8) hours/day of SB was associated with a significant 2.04 (95%CI = 1.50-2.76) times higher odds for WTD, while a 1-h increase in SB per day was associated with 1.11 (95%CI = 1.06-1.16) times higher odds for WTD. Mediation analysis showed that sleep problems, depression, loneliness, perceived stress, and social network explained a modest proportion of the association between SB and WTD (mediated percentage 9.3%-14.8%). The present cross-sectional study found that increasing or higher levels of SB is positively associated with WTD. Addressing the identified potential mediators may reduce WTD among people who are sedentary. However, future longitudinal and intervention studies are needed to make concrete recommendations.

Artificial neural network inference analysis identified novel genes and gene interactions associated with skeletal muscle aging.

BACKGROUND: Sarcopenia is an age-related muscle disease that increases the risk of falls, disabilities, and death. It is associated with increased muscle protein degradation driven by molecular signalling pathways including Akt and FOXO1. This study aims to identify genes, gene interactions, and molecular pathways and processes associated with muscle aging and exercise in older adults that remained undiscovered until now leveraging on an artificial intelligence approach called artificial neural network inference (ANNi). METHODS: Four datasets reporting the profile of muscle transcriptome obtained by RNA-seq of young (21-43 years) and older adults (63-79 years) were selected and retrieved from the Gene Expression Omnibus (GEO) data repository. Two datasets contained the transcriptome profiles associated to muscle aging and two the transcriptome linked to resistant exercise in older adults, the latter before and after 6 months of exercise training. Each dataset was individually analysed by ANNi based on a swarm neural network approach integrated into a deep learning model (Intelligent Omics). This allowed us to identify top 200 genes influencing (drivers) or being influenced (targets) by aging or exercise and the strongest interactions between such genes. Downstream gene ontology (GO) analysis of these 200 genes was performed using Metacore (Clarivate™) and the open-source software, Metascape. To confirm the differential expression of the genes showing the strongest interactions, real-time quantitative PCR (RT-qPCR) was employed on human muscle biopsies obtained from eight young (25 ± 4 years) and eight older men (78 ± 7.6 years), partaking in a 6-month resistance exercise training programme. RESULTS: CHAD, ZDBF2, USP54, and JAK2 were identified as the genes with the strongest interactions predicting aging, while SCFD1, KDM5D, EIF4A2, and NIPAL3 were the main interacting genes associated with long-term exercise in older adults. RT-qPCR confirmed significant upregulation of USP54 (P = 0.005), CHAD (P = 0.03), and ZDBF2 (P = 0.008) in the aging muscle, while exercise-related genes were not differentially expressed (EIF4A2 P = 0.99, NIPAL3 P = 0.94, SCFD1 P = 0.94, and KDM5D P = 0.64). GO analysis related to skeletal muscle aging suggests enrichment of pathways linked to bone development (adj P-value 0.006), immune response (adj P-value <0.001), and apoptosis (adj P-value 0.01). In older exercising adults, these were ECM remodelling (adj P-value <0.001), protein folding (adj P-value <0.001), and proteolysis (adj P-value <0.001). CONCLUSIONS: Using ANNi and RT-qPCR, we identified three strongly interacting genes predicting muscle aging, ZDBF2, USP54, and CHAD. These findings can help to inform the design of nonpharmacological and pharmacological interventions that prevent or mitigate sarcopenia.

Research on biomarkers using innovative artificial intelligence systems in breast cancer.

Cancer is highly diverse and heterogeneous. Accurate and rapid analysis of the characteristics of individual cancer cells, using a complex array of big data that includes various clinicopathological features and molecular mechanisms, is crucial for advancing precision medicine. In recent years, experts in biomedical sciences and data sciences have explored the potential of artificial intelligence (AI) to analyze such extensive data sets. The next phase of AI-based medical research on cancer should focus on the practical applications of AI tools and how they can be effectively used in actual medical research settings. Recently, translational research that leverages AI and comprehensive genetic analysis data has emerged as a significant research focus. This field represents an opportunity for groundbreaking discoveries to be shared globally. To further precision medicine in clinical practice, it is vital to develop sophisticated AI tools for cancer research. These tools should not only identify potential therapeutic targets through comprehensive genetic analysis but also predict therapeutic outcomes in clinical settings.

Alcohol and arterial stiffness in middle-aged and older adults: Cross-sectional evidence from the UK Biobank study.

BACKGROUND: The association between arterial stiffness and alcohol consumption is still controversial. We investigated this relationship by performing continuous analysis in men drinking only beer/cider, and women drinking only red wine. METHODS: This cross-sectional study involved participants aged 40-69 years consisting of 9029 men who drank only beer/cider, and 6989 women drinking only red wine. Alcohol consumption was captured by self-reported questionnaire and reported as units per week, where one unit is equal 10 mL pure ethanol. Arterial stiffness index (ASI) was estimated using photoplethysmography. RESULTS: In men consuming a mean 17.8 (5th and 95th percentiles, 2.6-76.7) units/week, ASI increased by heptiles (sevenths) of alcohol captured from beer/cider consumption and after adjusting for age (9.14, 9.40, 9.51, 9.53, 9.80, 9.80, 10.00 m/s; p-trend < 0.001) and after full adjustment (9.29, 9.46. 9.55, 9.55, 9.73, 9.73, 9.75 m/s; p-trend = 0.013). Similarly, in women consuming a mean 8.1 (1.6-29.3) units/week, ASI increased by heptiles of alcohol captured from red wine consumption and after adjusting for age (8.05, 8.05, 8.05, 8.11, 8.17, 8.30, 8.45 m/s; p-trend = 0.012) and borderline significant after full adjustment (8.05, 8.07, 8.05, 8.07, 8.11, 8.22, 8.43 m/s; p-trend = 0.055). These associations were confirmed in multivariable-adjusted regression analysis in all men, men younger and older than 50 years, and when consuming more than 14 units per week. Similarly, these associations were confirmed in all women, women older than 50 years, and in those consuming more than 14 units per week. CONCLUSIONS: Positive linear relationships exist between arterial stiffness and alcohol, irrespective of whether captured from beer/cider consumption in men or red wine consumption in women. No evidence existed to support the notion that our arteries benefit from any level of alcohol consumption.

Association between self-reported visual symptoms (suggesting cataract) and self-reported fall-related injury among adults aged ≥ 65 years from five low- and middle-income countries.

BACKGROUND: Cataracts may increase risk for falls but studies on this topic from low- and middle-income countries (LMICs) are scarce. Therefore, we examined the cross-sectional association between self-reported visual symptoms (suggesting cataract) and self-reported injurious falls in nationally representative samples of adults aged ≥ 65 years from five LMICs (China, Ghana, India, Mexico, and Russia). METHODS: Data from the WHO Study on global AGEing and adult health (SAGE) were analysed. Self-reported information on past 12-month fall-related injury and cataract based on symptoms were collected. Multivariable logistic regression and meta-analyses were conducted to assess associations. RESULTS: Data on 13,101 people aged ≥ 65 years were analysed [mean (SD) age 72.5 (11.3) years; 45.2% males]. The overall prevalence of self-reported fall-related injury and visual symptoms (suggesting cataract) were 4.9% and 29.4%, respectively. There was a positive association between self-reported visual symptoms (suggesting cataract) and fall-related injury (i.e., OR > 1) in all five countries but statistical significance was reached in three: China (OR = 1.60; 95% CI = 1.08-2.35), India (OR = 1.96; 95% CI = 1.15-3.35), and Russia (OR = 3.58; 95% CI = 2.06-6.24). The pooled OR including all five countries based on a meta-analysis was OR = 1.88 (95% CI = 1.32-2.68). CONCLUSIONS: Self-reported visual symptoms (suggesting cataract) were associated with higher odds for self-reported injurious falls among older adults in LMICs. Expanding availability of cataract surgery in LMICs may also have the additional benefit of reducing falls among older people.

Systemic Inflammation, the Peripheral Blood Transcriptome, and Primary Melanoma.

Peripheral blood transcriptomes from 383 patients with newly diagnosed melanoma were subjected to differential gene expression analysis. The hypotheses were that impaired systemic immunity is associated with poorer prognosis (thicker tumors and fewer tumor-infiltrating lymphocytes) and evidence of systemic inflammation (high-sensitivity CRP and fibrinogen levels). Higher fibrinogen levels were associated with thicker primary tumors. In single-gene analysis, high-sensitivity CRP levels were significantly associated with higher blood CD274 expression (coding for PD-L1), but each was independently prognostic, with high-sensitivity CRP associated with increased mortality and higher CD274 protective, independent of age. Pathway analysis identified downregulation of immune cell signaling pathways in the blood of people with thicker tumors and notable upregulation of signal transducer and activator of transcription 1 gene STAT1 in people with brisk tumor-infiltrating lymphocytes. Transcriptomic data provided evidence for increased NF-kB signaling with higher inflammatory markers but with reduction in expression of HLA class II molecules and higher CD274, suggesting that aberrant systemic inflammation is a significant mediator of reduced immune function in melanoma. In summary, transcriptomic data revealed evidence of reduced immune function in patients with thicker tumors and fewer tumor-infiltrating lymphocytes at diagnosis. Inflammatory markers were associated with thicker primaries and independently with death from melanoma, suggesting that systemic inflammation contributes to that reduced immune function.

Temporal gene signature of myofibroblast transformation in Peyronie's disease: first insights into the molecular mechanisms of irreversibility.

BACKGROUND: Transformation of resident fibroblasts to profibrotic myofibroblasts in the tunica albuginea is a critical step in the pathophysiology of Peyronie's disease (PD). We have previously shown that myofibroblasts do not revert to the fibroblast phenotype and we suggested that there is a point of no return at 36 hours after induction of the transformation. However, the molecular mechanisms that drive this proposed irreversibility are not known. AIM: Identify molecular pathways that drive the irreversibility of myofibroblast transformation by analyzing the expression of the genes involved in the process in a temporal fashion. METHODS: Human primary fibroblasts obtained from tunica albuginea of patients with Peyronie's disease were transformed to myofibroblasts using transforming growth factor beta 1 (TGF-ß1). The mRNA of the cells was collected at 0, 24, 36, 48, and 72 hours after stimulation with TGF-ß1 and then analyzed using a Nanostring nCounter Fibrosis panel. The gene expression results were analyzed using Reactome pathway analysis database and ANNi, a deep learning-based inference algorithm based on a swarm approach. OUTCOMES: The study outcome was the time course of changes in gene expression during transformation of PD-derived fibroblasts to myofibroblasts. RESULTS: The temporal analysis of the gene expression revealed that the majority of the changes at the gene expression level happened within the first 24 hours and remained so throughout the 72-hour period. At 36 hours, significant changes were observed in genes involved in MAPK-Hedgehog signaling pathways. CLINICAL TRANSLATION: This study highlights the importance of early intervention in clinical management of PD and the future potential of new drugs targeting the point of no return. STRENGTHS AND LIMITATIONS: The use of human primary cells and confirmation of results with further RNA analysis are the strengths of this study. The study was limited to 760 genes rather than the whole transcriptome. CONCLUSION: This study is to our knowledge the first analysis of temporal gene expression associated with the regulation of the transformation of resident fibroblasts to profibrotic myofibroblasts in PD. Further research is warranted to investigate the role of the MAPK-Hedgehog signaling pathways in reversibility of PD.

Global Trends in the Prevalence of Alcohol Consumption Among School-Going Adolescents Aged 12-15 Years.

PURPOSE: Adolescent alcohol consumption is detrimental to multiple facets of health. However, there is a scarcity of data available on time trends in adolescents' alcohol consumption particularly from non-Western countries and low- and middle-income countries. Thus, we examined the temporal trend of alcohol use in a large representative sample of school-going adolescents aged 12-15 years from 22 countries in Africa, Asia, and the Americas. METHODS: Data from the Global School-based Student Health Survey were analyzed. Alcohol consumption referred to consuming alcohol on at least one day in the past 30 days. Crude linear trends of past 30-day alcohol consumption by country were assessed by linear regression models. RESULTS: Data on 135,426 adolescents aged 12-15 years were analyzed [mean (standard deviation) age 13.8 (1.0) years; 52.0% females]. The overall mean prevalence of past 30-day alcohol consumption was 14.1%. Of the 22 countries included in the study, increasing, decreasing, and stable trends were observed in 3, 8, and 11 countries, respectively. Specifically, significant increases were observed in Benin between 2009 (16.1%) and 2016 (38.6%), Myanmar between 2007 (0.9%) and 2016 (3.6%), and Vanuatu between 2011 (7.6%) and 2016 (12.2%). The most drastic decrease was observed in Samoa between 2011 (34.5%) and 2017 (9.8%), but the rate of decrease was modest in most countries. DISCUSSION: Among school-going adolescents, decreasing trends in alcohol consumption were more common than increasing trends, but the rate of decrease was limited in most countries, suggesting that more global action is required to curb adolescent alcohol consumption.