Search Results (7,027)

Objectives: To establish normative data for anterior segment parameters in healthy pediatric and adult populations using swept-source optical coherence tomography (SS-OCT), and to evaluate the influence of age and sex on these parameters. Methods: This retrospective study included the right eyes of 390 healthy participants. Subjects were divided into three age groups: Group 1 (6–17 years, n = 97), Group 2 (18–45 years, n = 144), and Group 3 (46–77 years, n = 149). All patients were categorized according to their biological sex as female and male. Exclusion criteria were corneal pathology, prior intraocular/refractive surgery, recent contact lens use, severe dry eye, ectatic disorders, low-quality imaging, and refractive error of ±2.0 D or greater. Measurements of anterior and posterior keratometry, total corneal power (TCP), central corneal thickness (CCT), thinnest corneal thickness (TCT), pupil diameter (PD), lens thickness (LT), and white-to-white distance (WTW) were obtained using the Anterion^® SS-OCT system. Data were analyzed using SPSS software. Results: Group 1 demonstrated the highest PD and CCT values, whereas LT was lowest. In adults, LT increased with age and was significantly higher in males older than 45 years. Keratometric analysis revealed greater anterior and total steep astigmatism in the pediatric group, independent of sex. Adult females had significantly higher anterior and posterior keratometry values compared with males. In the pediatric cohort, females exhibited greater CCT, while WTW varied with age. PD decreased with age, whereas LT increased. Conclusions: Anterior segment parameters measured with SS-OCT show significant variations across different age groups and between sexes. Normative data, particularly for pediatric and adult populations, may serve as valuable reference values in keratorefractive surgical planning and corneal pathology assessment. Future studies with larger cohorts, especially in pediatric populations, are warranted. Full article

Introduction: Cigarette smoking is unquestionably associated with an increase in morbidity and mortality worldwide, exerting significant adverse effects on respiratory health. The impact of tobacco persists in the epigenome long after smoking cessation. Furthermore, the offspring of smokers may also be affected by the detrimental effects of smoking. Material and methods: The modifications made to the body, such as DNA methylation, histone modification, and regulation by non-coding RNAs, do not change the DNA sequence but can influence gene expression. In respiratory disease, multigenerational effects have been reported in humans, with an increased risk of asthma or COPD and decreased lung function in offspring, despite them not being exposed to smoke. Prenatal nicotine exposure leads to pulmonary pathology that persists across three consecutive generations, supported by animal studies conducted by Rehan et al. Significant advances in high-throughput genomic and epigenomic technologies have enabled the discovery of molecular phenotypes. These either reflect or are influenced by them. Due to the hidden environmental effects and the rise of artificial intelligence (AI) in biomedical research, new predictive models are emerging that not only explain complex data but also enable earlier detection and prevention of smoking-related diseases. In this narrative review, we synthesise the latest research on how smoking affects gene regulation and chromatin structure, emphasising how tobacco can increase vulnerability to multiple diseases. Discussion: For many years, it was widely believed that diseases are solely inherited through genetics. However, recent research in epigenetics has led to a significant realisation: environmental factors play a crucial role in an individual’s life. External influences leave a mark on DNA that can influence future health and offer insights into potential illnesses. In this context, it is possible that in the future, doctors might treat people not as a whole but as individual beings, with personalised medication, tests, and other approaches. Conclusions: The accumulated evidence suggests that exposure to various environmental factors is associated with multigenerational changes in gene expression patterns, which may contribute to increased disease risk. The application of artificial intelligence in this domain is currently a crucial tool for researching potential future health issues in individuals, and it holds a powerful prospect that could transform current medical and scientific practice. Full article

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease worldwide, with proximal tubular epithelial cells (PTECs) playing a central role in its pathogenesis. Under hyperglycemic conditions, PTECs drive a pathological triad of inflammation, apoptosis, and fibrosis. Recent advances reveal that these processes interact synergistically to form a self-perpetuating vicious cycle, rather than operating in isolation. This review systematically elucidates the molecular mechanisms underlying this crosstalk in PTECs. Hyperglycemia induces reactive oxygen species (ROS) overproduction, advanced glycation end products (AGEs) accumulation, and endoplasmic reticulum stress (ERS), which collectively activate key inflammatory pathways (NF-κB, NLRP3, cGAS-STING). The resulting inflammatory milieu triggers apoptosis via death receptor and mitochondrial pathways, while apoptotic cells release damage-associated molecular patterns (DAMPs) that further amplify inflammation. Concurrently, fibrogenic signaling (TGF-β1/Smad, Hippo-YAP/TAZ) promotes epithelial–mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Crucially, the resulting fibrotic microenvironment reciprocally exacerbates inflammation and apoptosis through mechanical stress and hypoxia. Quantitative data from preclinical and clinical studies are integrated to underscore the magnitude of these effects. Current therapeutic strategies are evolving toward multi-target interventions against this pathological network. We contrast the paradigm of monotargeted agents (e.g., Finerenone, SGLT2 inhibitors), which offer high specificity, with that of multi-targeted natural product-based formulations (e.g., Huangkui capsule, Astragaloside IV), which provide synergistic multi-pathway modulation. Emerging approaches (metabolic reprogramming, epigenetic regulation, mechanobiological signaling) hold promise for reversing fibrosis. Future directions include leveraging single-cell technologies to decipher PTEC heterogeneity and developing kidney-targeted drug delivery systems. We conclude that disrupting the inflammation–apoptosis–fibrosis vicious cycle in PTECs is central to developing next-generation therapies for DN. Full article

Background: Neoadjuvant chemotherapy (NAC) is a standard preoperative intervention for early-stage breast cancer (BC). Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a critical tool for evaluating treatment response and pathological complete response (pCR) following NAC. Computational modeling offers a robust framework to simulate tumor growth dynamics and therapy response, leveraging patient-specific data to enhance predictive accuracy. Despite this potential, integrating imaging data with computational models for personalized treatment prediction remains underexplored. This case study presents a proof-of-concept prognostic tool that bridges oncology, radiology, and computational modeling by simulating BC behavior and predicting individualized NAC outcomes. Methods: CE-MRI scans, clinical assessments, and blood samples from three retrospective NAC patients were analyzed. Tumor growth was modeled using a system of partial differential equations (PDEs) within a reaction–diffusion mass transfer framework, incorporating patient-specific CE-MRI data. Tumor volumes measured pre- and post-treatment were compared with model predictions. A 20% error margin was applied to assess computational accuracy. Results: All cases were classified as true positive (TP), demonstrating the model’s capacity to predict tumor volume changes within the defined threshold, achieving 100% precision and sensitivity. Absolute differences between predicted and observed tumor volumes ranged from 0.07 to 0.33 cm³. Virtual biomarkers were employed to quantify novel metrics: the biological conversion coefficient ranged from 4 × 10⁻⁷ to 6 × 10⁻⁶ s^-1, while the pharmacodynamic efficiency coefficient ranged from 1 × 10⁻⁷ to 4 × 10⁻⁴ s^-1, reflecting intrinsic tumor biology and treatment effects, respectively. Conclusions: This approach demonstrates the feasibility of integrating CE-MRI and computational modeling to generate patient-specific treatment predictions. Preliminary model training on retrospective cohorts with matched BC subtypes and therapy regimens enabled accurate prediction of NAC outcomes. Future work will focus on model refinement, cohort expansion, and enhanced statistical validation to support broader clinical translation. Full article

Objective/Background: Pupil diameter varies across individuals, limiting its reliability in assessing cerebral pathologies, particularly in comatose patients following subarachnoid haemorrhage (SAH). The Dangerous Alarming Diameter Assessment (DADA) index, defined as the ratio of iris surface to pupil surface, may offer a more precise diagnostic tool. This study evaluates the efficacy of the DADA index compared to pupil diameter in predicting neurodegeneration in the Edinger–Westphal nucleus (EWN) and diagnosing brain death in an SAH model. Methods: Twenty-three rabbits were divided into Control (n = 5), Sham (n = 5), and Study (SAH, n = 12) groups. Pupil diameter and DADA index values were measured via spectral-domain optical coherence tomography (SD-OCT) in groups at post-intervention (0.75 cc serum physiologic injection for Sham, 0.75 cc autologous blood injection for Study). After one week, animals were sacrificed, and EWN degenerated neuron density was quantified using stereological methods. Data were analysed with Kruskal–Wallis and Mann–Whitney U tests, with correlations assessed for pupil diameter and DADA index against EWN neurodegeneration. Results: Pupil diameter assessment classified all 12 study group subjects as deceased, primarily due to fixed and dilated pupils. In contrast, the DADA index identified only 8 of these 12 subjects as deceased, with EWN degenerated neuron density exceeding 80%, while the remaining 4 subjects showed less than 80% neurodegeneration, indicating viability. Strong negative correlations were observed between pupil diameter (r = −0.972, p < 0.001) and DADA index (r = −0.977, p < 0.001) with EWN neurodegeneration. The DADA index demonstrated superior precision in distinguishing severe neurodegeneration, suggesting its potential as a criterion for brain death assessment. Conclusions: The DADA index provides a more accurate and nuanced evaluation of EWN neurodegeneration compared to pupil diameter, offering a promising diagnostic tool for brain death in SAH-induced comatose states, with potential implications for future brain transplantation diagnostics. Full article

Gastric diseases represent a significant challenge to global health. A comprehensive understanding of their complex molecular mechanisms, particularly the pathways of molecular progression in precancerous lesions, is essential for enhancing diagnosis and treatment. StomachDB, the first comprehensive multi-omics database dedicated to gastric diseases, has been developed to address these research needs. This database integrates 6 types of biological data: genomics, transcriptomics, emerging single-cell and spatial transcriptomics, proteomics, metabolomics, and therapeutic-related information. It encompasses 44 gastric-related pathologies, including various forms of gastric cancer, gastric ulcers, and gastritis, primarily involving humans and mice as model organisms. The database compiles approximately 2.5 million curated and standardized profiles, along with 268,394 disease-gene associations. The user-friendly analytics platform provides tools for browsing, querying, visualizing, and downloading data, facilitating systematic exploration of multi-omics features. This integrative approach addresses the limitations of single-omics analyses, such as data heterogeneity and insufficient analytical dimensions. Researchers can investigate the clinical significance of target genes (e.g., CDH1) across different omics levels and explore potential regulatory mechanisms. Furthermore, StomachDB emphasizes the discovery of therapeutic targets by cataloging interactions among chemical drugs, traditional herbal medicines, and probiotics. As an open-access resource, it serves as a powerful tool for studying complex biological interactions and regulatory mechanisms. Full article

A significant gap in specific nutritional guidelines for ruminants with compromised health exists. Due to their unique anatomy, physiology, and metabolic processes, further research is needed to establish accurate, evidence-based recommendations tailored to these animals. This review highlights the critical role of clinical ruminant nutrition and provides provisional recommendations based on studies in other species (e.g., changes in nutrient requirements in different morbidities available for humans and less for companion animals). These suggestions should be interpreted cautiously until more definitive, species-specific data become available. The review includes the foundational principles of clinical nutrition in ruminants, with particular emphasis on the pathophysiology of nutrient utilization. It explores the roles of energy, protein, vitamins, and minerals during illness or injury and discusses how these nutrients can be strategically applied in clinical interventions. Considerations for designing diets for compromised ruminants are also addressed, considering both physiological needs and the challenges posed by illness and injury states. Practical aspects of diet delivery during treatment are examined, including the indications, benefits, limitations, and potential side effects of route of feeding. Clinical nutrition can be administered orally, enterally (including rumen delivery) or parenteral, depending on the localization of the pathology and the integrity of the alimentary tract. Nutrients should be provided based on livestock requirements and pathophysiology and severity of the primary morbidity. Oral or ruminal provision of diet should be prioritized to maintain rumen functionality. Additionally, a list of pharmaconutrients with potential clinical applications in ruminant medicine is presented to encourage future research and integration into veterinary practice. The success of clinical nutritional interventions can be measured by improvements in appetite, behavior, and health of the compromised ruminant. Full article

Background: Small bowel adenocarcinoma (SBA) is a rare malignancy, and the role of adjuvant chemotherapy following curative resection remains unclear owing to limited supporting evidence. In this study, we aimed to evaluate the real-world effectiveness of adjuvant chemotherapy in patients with resected SBA. Methods: We retrospectively reviewed data from patients with localized SBA who underwent curative resection at a single tertiary referral center in Southern Thailand between 2005 and 2024. Results: Of 128 patients diagnosed with SBA, 52 (40.6%) had localized disease and underwent curative resection. Among them, 29 patients (55.8%) received adjuvant chemotherapy and 23 (44.2%) were managed with observation alone. The median disease-free survival (DFS) was 18.1 and 16.2 months in the adjuvant chemotherapy and observation groups, respectively (p = 0.642). The median overall survival (OS) was 42.8 vs. 26.7 months, respectively (p = 0.179). Subgroup analyses revealed trends favoring adjuvant chemotherapy in patients with pathological T4 disease, nodal involvement, younger age, and non-underweight body mass indices. Positive surgical margins were associated with inferior DFS, and T4 stage was associated with worse OS. Disease recurrence occurred in 59% of patients, predominantly as distant metastasis. Conclusions: Adjuvant chemotherapy showed a trend toward improved survival, particularly in patients with high-risk features; however, these findings should be interpreted with caution given the limited sample size and retrospective design. These results highlight the importance of individualized treatment decisions and underscore the need for larger multi-institutional studies to clarify the role of adjuvant chemotherapy and identify prognostic biomarkers for this rare malignancy. Full article

Background/Objectives: In a series of 33 patients with advanced penile squamous cell carcinoma (PSCC), we evaluated tissue factor (TF), TROP2, and nectin-4 protein expression as potential therapeutic targets. Expression levels of these proteins were also correlated to clinicopathological characteristics, including high-risk human papillomavirus (HPV), CDKN2A (p16) status, and aberrant p53 expression. Methods: A tissue microarray (TMA) was constructed with three cores per patient tumor (99 total cores). Anti-TF antibody staining was performed by immunohistochemistry, and H-scores for membrane and cytoplasm staining were assessed (range 0–300). The percentage of cores and patient tumors staining positive for TF (≥10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) and H-scores were described and compared with HPV and p16 status. The association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), aberrant p53 expression, recurrence-free survival (RFS), and cancer-specific survival (CSS) was assessed. Nectin-4 and TROP2 staining and their association with clinical/pathological data were determined in a similar manner. Results: TF staining was evident in 26 (81.3%) of the cohort and was more prominent in HPV-negative tumors in both the membrane (H-score 69.6 vs. 18.8; p = 0.003) and cytoplasm (H-score 59.2 vs. 17.7, p = 0.007). Cytoplasmic (H-score 61.7 vs. 11.7, p < 0.001) and membrane TF staining (H-score 71.7 vs. 15.0, p < 0.001) favored p16-negative tumors. The p53 status was more likely to be aberrant in the higher TF staining samples (cytoplasm H-score 61.7 vs. 18.3, p = 0.012; membrane H-score 67.5 vs. 20.3, p = 0.006). We observed an association with TROP2 staining and positive p16 status (membrane H-score 120.3 vs. 85, p = 0.052; cytoplasmic H-score 135 vs. 107.5, p = 0.041). We observed an association of TROP2 staining with positive LVI (membrane H-score 136.7 vs. 66.7, p = 0.014; cytoplasmic H-score 110 vs. 93.3, p = 0.04). We found no association between TF, TROP2, or nectin-4 staining with CSS or RFS; however, we suspect that this was due to our small sample size. Conclusions: Our results indicate that TF was expressed in the majority of advanced PSCC with enhanced expression among HPV-independent, p53-aberrant tumors and may represent a novel therapy target in advanced PSCC. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The absence of reliable fluid biomarkers continues to hinder early diagnosis and effective monitoring of disease progression. Circulating microRNAs (cmiRNAs) are potential candidates, given their stability in biofluids and their ability to mirror pathological processes. We conducted a longitudinal study in 30 early-stage levodopa-naive PD patients (22 men, 8 women). Serum samples were collected at baseline (T0) and at a follow-up time point two years later (T2). A panel of MicroRNAs (miRNAs) (miR-146a-5p, miR-34a-5p, miR-155-5p, miR-29a-3p, miR-106a-5p) were quantified by quantitative real-time PCR. Data were expressed as relative expression (2^−ΔCt), and statistical analyses included sex-stratified comparisons and paired tests for longitudinal changes. At baseline, no significant differences were found in the expression of the miRNAs between male and female PD patients. In contrast, longitudinal within-subject analysis revealed a highly significant upregulation in miR-146a-5p expression from T0 to T2 in both sexes (p < 0.0001). No other miRNAs in the panel exhibited significant changes over time. CmiR-146a-5p levels rise markedly over time in PD patients, independent of sex, suggesting that this miRNA could be a dynamic biomarker of disease progression. Full article

Background: Background: Endometriosis affects 10% of women of reproductive age. Despite the well-known association between endometriosis and infertility, the mechanisms underlying this association remain to be elucidated. Methods: Implantation and pregnancy success rates were evaluated by a retrospective study of patients that underwent IVF using euploid embryos comparing healthy vs. endometriosis patients. To study the early embryo–endometrial dialogue, an interactome network was constructed using public RNAseq data from normal secretory-phase endometrial samples and day-5 blastocyst. Public bulk and single-cell RNAseq data from endometrial samples of endometriosis patients were used to detect alterations in the interactome. Results: Endometriosis patients required significantly more IVF attempts compared to those without endometrial pathologies; however, once pregnancy was achieved, the evolution of both groups was similar. The interactome network between normal endometrium and day-5 blastocyst showed a significant enrichment of pathways associated with tissue remodelling, angiogenesis, and immune regulation, which were altered in endometriosis patients. Endometriosis patients also presented an increased frequency and activation of NK, CD4⁺, and CD8⁺ cells, which interfere with embryo–endometrial dialogue. Conclusions: We identified key molecular processes affected by endometriosis specifically involved in the early interaction between the blastocyst, decidual, and resident immune cells, that may underline the reported fertility problems associated with endometriosis. Full article

Sexual dimorphism influences immune responses, cancer progression, and therapeutic outcomes, yet its metabolic underpinnings remain underexplored. Metabolomics enables the comprehensive profiling of biochemical pathways that shape sex-based differences in immune function and immunotherapy efficacy. Meta-analytic data indicate that men achieve a larger overall survival benefit from immune checkpoint inhibitors than women (pooled hazard ratio 0.72, 95% CI 0.65–0.79 vs. 0.86, 95% CI 0.79–0.93), while women may experience higher major pathologic response rates in neoadjuvant settings. At the biomarker level, elevated kynurenine-to-tryptophan ratios—reflecting indoleamine 2,3-dioxygenase activity—and distinct lipidomic signatures associate with reduced immunotherapy efficacy and may vary by sex. Sex-specific differences in microbiome-derived metabolites, including short-chain fatty acids, further modulate systemic immunity and treatment response. Ongoing clinical investigations combine hormone modulation with immune checkpoint blockade and increasingly integrate metabolomic profiling to identify predictors of benefit and toxicity. This review will synthesize meta-analytic and mechanistic evidence on sex differences in immunotherapy outcomes, highlight metabolomic biomarkers linked to response, and summarize ongoing clinical trials that incorporate metabolomics to guide sex-aware precision oncology. Understanding sex-specific metabolic pathways can refine patient stratification and optimize immunotherapeutic strategies. Full article

Background: Mitral valve prolapse (MVP) is the most common valvular abnormality in the general population and has been linked to mitral regurgitation, arrhythmias, and sudden cardiac death. Its prevalence and prognostic significance in athletes remain uncertain, raising important questions for pre-participation screening, eligibility for competition, and long-term follow-up. Methods: We systematically searched PubMed, Scopus, and EMBASE databases from inception through August 2025 for original studies reporting MVP prevalence in athletes, diagnosed by echocardiography or pathological assessment. Data on study characteristics, diagnostic definitions, prevalence, arrhythmias, and outcomes were independently extracted by three reviewers. Methodological quality was appraised using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Twelve studies published between 1987 and 2024 met inclusion criteria, enrolling 19,463 athletes from diverse sports and competitive levels. A total of 407 MVP cases were identified, corresponding to a crude pooled prevalence of 2.4%. Prevalence estimates varied substantially (0.2–20%), reflecting heterogeneity in study populations and diagnostic definitions. When all studies were pooled using a random-effects model, the overall prevalence was 2.0% (95% CI 1.2–2.8%). A sensitivity analysis restricted to contemporary, unselected athletic cohorts yielded a prevalence of 1.1% (95% CI 0.4–1.9%), closely aligning with population-based estimates. Ventricular arrhythmias were more frequent than supraventricular arrhythmias, particularly in association with bileaflet prolapse, leaflet thickening, or significant mitral regurgitation. Most athletes were asymptomatic, and only one prospective study provided long-term follow-up, confirming a generally benign prognosis, though rare adverse events (atrial fibrillation, valve surgery) were documented. Conclusions: MVP is relatively uncommon in athletes and occurs at rates similar to the general population. In most cases, prognosis is favorable and should not preclude sports participation. Nonetheless, recognition of high-risk phenotypes with arrhythmogenic potential highlights the need for individualized evaluation and tailored surveillance strategies in sports cardiology practice. Full article

People living with the human immunodeficiency virus (PLWH) are continually subjected to challenges involving the development of non-acquired immunodeficiency syndrome (AIDS)-related comorbidities despite the effectiveness of highly active antiretroviral therapy (HAART). Exacerbated oxidative stress, which is intrinsically linked to chronic inflammation, is implicated in non-AIDS comorbidities, including the increased risk of cardiovascular disease (CVD) observed in PLWH. Here, we review evidence on the potential pathological implications of myeloperoxidase (MPO), a leukocyte-derived enzyme and a key mediator of oxidative stress and inflammation, in driving CVD-related complications in PLWH. A systematic review approach was taken to identify relevant clinical studies through searches of Cochrane Libraries, PubMed, Web of Science, ScienceDirect, and Google Scholar, up to the 30 June 2025. The summarized data appraised clinical studies (n = 14) on adults (n = 1445) with a mean age of 45 years reporting on the association between MPO and enhanced lipid peroxidation marked by elevated concentrations of oxidized low-density lipoprotein cholesterol (oxLDL-C) in PLWH. Such results were consistent with elevated inflammatory markers, including high sensitivity C-reactive protein (hsCRP), which was also linked with endothelial dysfunction. There is a lack of evidence linking the duration of HAART to MPO levels or an increased risk of CVD. However, there is room to explore whether enhanced levels of oxLDL-C, in association with sustained MPO activation, could drive CVD risk in PLWH. The present review provides essential information on the pathological relevance of MPO in endothelial dysfunction and CVD risk in PLWH. Full article

This study presents a three-dimensional finite element (FE) analysis of the human foot bone structure under mid-stance loading during race walking. A subject-specific biomodel comprising 26 bones and over 40 ligaments was reconstructed from computed tomography (CT) data using Materialise Mimics Research 21.0 and 3-Matic Research 13.0, and subsequently analyzed in ANSYS Workbench 2024 R1. The model included explicit cortical, trabecular, and ligamentous volumes, each assigned linear-elastic, isotropic material properties based on biomechanical literature data. Boundary conditions simulated the mid-stance phase of race walking, applying a distributed plantar pressure of 0.25 MPa over the metatarsal and phalangeal regions. Numerical simulations yielded maximum total displacements of 0.00018 mm, maximum von Mises stresses of 0.171 MPa, and maximum strains of 2.5 × 10⁻⁵, all remaining well within the elastic range of bone tissue. The results confirm the model’s numerical stability, geometric fidelity, and capacity to represent physiologically realistic loading responses. The developed framework demonstrates the potential of high-resolution, image-based finite element modelling for investigating stress–strain patterns of the foot during athletic gait, and establishes a reproducible reference for future analyses involving pathological gait, orthotic optimisation, and musculoskeletal load assessment in sports biomechanics. Full article