Search Results (401)

Accurately estimating the radiation dose received by an individual is essential for evaluating potential damage caused by exposure to ionizing radiation. Most retrospective dosimetry methods require the time since exposure to be known and rely on calibration curves specific to that time point. In this work, we introduce a novel method tailored to the γ-H2AX assay, which is a protein-based biomarker for radiation exposure, that enables the estimation of both the radiation dose and the time of exposure within a plausible post-exposure interval. Specifically, we extend calibration curves available at two distinct time points by incorporating the biological decay of foci, resulting in a model that captures the joint dependence of foci count on both dose and time. We demonstrate the applicability of this approach using both real-world and simulated data. Full article

Benign prostatic hyperplasia (BPH) is a multifactorial condition that is highly prevalent and affects aging males. It frequently results in lower urinary tract symptoms (LUTS) and a reduced quality of life. While hormonal dysregulation and chronic inflammation have long been implicated in BPH pathogenesis, recent evidence highlights the role of physical activity in modulating prostate health. In this narrative review, evidence from quantitative studies examining the effect of exercise on BPH risk and symptom severity was first synthesized. Collectively, these studies suggest that regular physical activity is associated with a lower incidence and reduced progression of BPH. The potential mechanisms through which exercise may exert protective effects on the prostate were then explored. These include modulation of sympathetic nervous system activity, alterations in hormonal profiles (e.g., testosterone and insulin), suppression of chronic inflammation and oxidative stress, and the promotion of autophagy within prostatic tissue. Central to these mechanisms is the role of myokines—signaling molecules secreted by skeletal muscle during exercise. Key myokines, such as irisin, interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and myostatin, are reviewed in the context of prostate health. These molecules regulate inflammatory pathways, metabolic processes, and tissue remodeling. For instance, exercise-induced reductions in myostatin are linked to improved insulin sensitivity and decreased fat accumulation, while elevated irisin and BDNF levels may exert anti-inflammatory and metabolic benefits relevant to BPH pathophysiology. Although direct causal evidence linking myokines to BPH is still emerging, their biological plausibility and observed systemic effects suggest a promising avenue for non-pharmacological intervention. Future research should focus on identifying the specific myokines involved, elucidating their molecular mechanisms within the prostate, and evaluating their therapeutic potential in clinical trials. Full article

Background/Objectives: Maternal exposures are known to influence the risk of isolated cleft lip with or without cleft palate (CL/P)—a common and highly heritable birth defect with a multifactorial etiology. Methods: To identify new risk loci, we conducted a genome-wide gene–environment interaction (GEI) analysis of CL/P with maternal smoking and vitamin use in Filipinos (N_cases = 540, N_controls = 260). Since GEI analyses are typically low in power and the results can be difficult to interpret, we applied multiple testing frameworks to evaluate potential GEI effects: a one degree-of-freedom (1df) GxE test, the 3df joint test, and the two-step EDGE approach. Results: While no genome-wide significant interactions were detected, we identified 11 suggestive GEIs with smoking and 24 with vitamin use. Several implicated loci contain biologically plausible genes. Notable interactions with smoking include loci near FEZF1, TWIST2, and NET1. While FEZF1 is involved in early neuronal development, TWIST2 and NET1 regulate epithelial–mesenchymal transition, which is required for proper lip and palate fusion. Interactions with vitamins encompass CECR2—a chromatin remodeling protein required for neural tube closure—and FURIN, a critical protease during early embryogenesis that activates various growth factors and extracellular matrix proteins. The activity of both proteins is influenced by folic acid. Conclusions: Our findings highlight the critical role of maternal exposures in identifying genes associated with structural birth defects such as CL/P and provide new paths to explore for CL/P genetics. Full article

This study explores the application of spiking neural networks (SNNs) for click-through rate (CTR) prediction in personalized online advertising systems, introducing a novel hybrid model, the Temporal Rate Spike with Attention Neural Network (TRA–SNN). By leveraging the biological plausibility and energy efficiency of SNNs, combined with attention-based mechanisms, the TRA–SNN model captures temporal dynamics and rate-based patterns to achieve performance comparable to state-of-the-art Artificial Neural Network (ANN)-based models, such as Deep & Cross Network v2 (DCN-V2) and FinalMLP. The models were trained and evaluated on the Avazu and Digix datasets, using standard metrics like AUC-ROC and accuracy. Through rigorous hyperparameter tuning and standardized preprocessing, this study ensures fair comparisons across models, highlighting SNNs’ potential for scalable, sustainable deployment in resource-constrained environments like mobile devices and large-scale ad platforms. This work is the first to apply SNNs to CTR prediction, setting a new benchmark for energy-efficient predictive modeling and opening avenues for future research in hybrid SNN–ANN architectures across domains like finance, healthcare, and autonomous systems. Full article

The virus-first theory presents a model in which viral lineages emerged before cells. This proposal aims to give the theory greater relevance by offering a plausible evolutionary framework that explains both (i) the origin of viruses from prebiotic chemistry and (ii) how viruses contributed to the emergence of cells. Here, we propose that viruses should be understood as a distinct class of ribonucleoprotein (RNP) systems, some of which evolved directly from the RNP-world. In our model, simple progenotes produced capsid-like particles through the evolution of a single gene encoding a self-assembling peptide. This allowed the formation of icosahedral shells around RNA genomes, as observed today in certain viral families whose capsids consist of ~60 identical subunits derived from a single gene product. These early capsids enabled mobility and protection, representing key intermediates toward biological complexity. Over time, some of those populations acquired additional peptides and evolved more elaborate architectures. Finally, the incorporation of lipid-binding domains in those capsid-like peptides allowed the formation of proteolipidic membranes akin to those found in modern cells. This model provides a gradualistic and logically coherent evolutionary path from the RNP-world to the emergence of cellular life, emphasizing the foundational role of viruses in early evolution. Full article

Background/Objectives: The anti-Müllerian hormone (AMH) is a key biomarker of the ovarian reserve, correlating with ovarian follicle count, fertility outcomes, and menopause timing. Understanding its genetic determinants has broad implications for female reproductive health. However, prior genome-wide association studies (GWASs) have focused exclusively on women of European ancestry, limiting insights into diverse populations. Methods: We conducted a GWAS to identify genetic loci associated with circulating AMH levels in a sample of 1185 Samoan women from two independently recruited samples. Using a Cox mixed-effects model we accounted for AMH levels below detectable limits and meta-analysed the summary statistics using a fixed-effect model. To prioritize variants and genes, we used FUMA and performed colocalization and transcriptome-wide association analysis (TWAS). We also assessed whether any previously reported loci were replicated in our GWAS. Results: We identified eleven genome-wide suggestive loci, with the strongest signal at ARID3A (19-946163-G-C; p = 2.32 × 10⁻⁷) and replicated rs10093345 near EIF4EBP1. The gene-based testing revealed ARID3A and R3HDM4 as significant genes. Integrating GWAS results with expression quantitative trait loci via TWAS, we detected seven transcriptome-wide significant genes. The lead variant in ARID3A is in high linkage disequilibrium (r² = 0.79) with the known age-at-menopause variant 19-950694-G-A. Nearby KISS1R is a biologically plausible candidate gene that encodes the kisspeptin receptor, a regulator of ovarian follicle development linked to AMH levels. Conclusions: This study expands our understandings of AMH genetics by focusing on Samoan women. While these findings may be particularly relevant to Pacific Islanders, they hold broader implications for reproductive phenotypes such as the ovarian reserve, menopause timing, and polycystic ovary syndrome. Full article

Background/Objectives: Chronic illness after COVID-19 vaccination (longvax) lacks a therapeutic protocol anchored in pathophysiology. Persistent vaccine derived spike protein appears to trigger microvascular fibrin amyloid microclots, immune dysfunction, pathogen reactivation and multisystem injury. This article proposes an integrative approach, Vaxtherapy, to tackle these mechanisms. Methods: A narrative synthesis of peer reviewed literature from 2021 to 2025 on spike related injury and vaccine adverse events was conducted, supplemented by clinical case series and mechanistic observations from long COVID. The findings were arranged into a four stage therapeutic sequence ordered by pathophysiological precedence. Results: Stage one aims to reopen hypoperfused tissue through oral fibrinolytics that degrade fibrin amyloid resistant microclots; stage two intends to neutralise circulating or tissue bound spike via a receptor binding domain monoclonal antibody cocktail; stage three seeks to eliminate reactivated viral or microbial reservoirs with targeted antivirals or antimicrobials once perfusion is improved; and stage four aspires to support tissue repair with mitochondrial supplements and, when indicated, cell based therapies. Omitting or reordering stages may reduce efficacy or foster resistance. Conclusions: This hypothesis driven framework outlines a biologically plausible roadmap for longvax research. By matching interventions to specific mechanisms (fibrinolysis, spike neutralisation, pathogen clearance and regeneration), it aims to guide controlled trials and compassionate pilot programs directed at durable recovery rather than chronic symptom management. Full article

The role of vitamin D in reducing cardiovascular disease (CVD) risk remains debated despite growing evidence. Prospective observational studies consistently show that low serum 25-hydroxyvitamin D [25(OH)D] concentrations (below 40–50 nmol/L [16–20 ng/mL]) are associated with the highest risk of CVD incidence. In addition, a large prospective observational study found that serum 25(OH)D concentration was inversely correlated with CVD mortality rate to over 100 nmol/L. Randomized controlled trials have not generally demonstrated benefit due to faulty study designs, such as enrolling participants with baseline 25(OH)D levels > 50 nmol/L. However, a major trial found that 60,000 IU/month of vitamin D₃ supplementation reduced the risk of major cardiovascular events for participants with predicted 25(OH)D concentrations ≥ 50 nmol/L or taking statins or CV drugs by ~13 to ~17%. In addition, vitamin D supplementation studies have found modest reductions in several CVD risk factors. Other observational studies of vitamin D supplementation have reported reduced CVD risks (e.g., ischemic heart disease, hypertension, and myocardial infarction). Temporal ecological studies further support this relationship, revealing that CVD incidence rates are lowest in summer and CVD mortality rates are significantly higher in late winter—when 25(OH)D concentrations are lowest—compared to late summer. A previously reported analysis using eight of Hill’s criteria for causality in a biological system further strengthens the biological plausibility of vitamin D’s role in CVD risk reduction. Its role in modulating inflammation and oxidative stress, improving endothelial function, and reducing several cardiometabolic risk factors supports its inclusion as part of a comprehensive, multi-modal approach to cardiovascular health. Therefore, vitamin D should be considered an integral component in the prevention and management of CVD. Preferably, it should be used in combination with other nutritional supplements, a heart-healthy diet, and prescription medications to reduce the risk of CVD incidence. People should consider vitamin D₃ supplementation with at least 2000 IU/day (50 mcg/day) (more for those who are obese) when sun exposure is insufficient to maintain serum 25(OH)D concentrations above 75 nmol/L. To reduce CVD mortality rates, higher doses to achieve higher 25(OH)D concentrations might be warranted. Full article

A series of novel hybrid uracil derivatives incorporating the natural alkaloids caffeine or gramine, linked via 1,2,3-triazole ring, were synthetized using click chemistry. The structures of the obtained compounds were confirmed by spectroscopic methods, including ¹H NMR, ¹³C NMR, FT-IR, and mass spectrometry. The biological activity of hybrids was evaluated in vitro, including assessments of hemolytic activity, antioxidant potential, antifungal efficacy, and antibacterial activity. Additionally, molecular docking studies were conducted in silico for the most active antioxidant candidate. The results revealed that the hemocompatibility of the derivatives was structure-dependent. While caffeine-containing hybrids exhibited moderate-to-low cytoprotective activity under oxidative stress conditions, those incorporating gramine showed significantly higher potency. A plausible molecular mechanism underlying their cytoprotective activity is proposed. Several compounds also inhibited the growth of the plant pathogens Fusarium culmorum and Botrytis cinerea. The promising antioxidant and antifungal properties of selected uracil–alkaloid hybrids highlight their potential as multifunctional bioactive compounds for managing oxidative stress and controlling plant pathogens. Furthermore, the finding demonstrates the effectiveness of click chemistry as a versatile tool for the synthesis of bioactive heterocyclic compounds. Full article

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interfere with the endocrine system by mimicking or blocking the action of endogenous hormones such as estrogens, androgens, and thyroid hormones. This systematic review aims to evaluate the current epidemiological evidence linking EDC exposure with adverse reproductive outcomes in males and females of reproductive age. A total of 14 observational studies published between 2014 and 2024 were included following structured searches in PubMed, Scopus, and Google Scholar. The most commonly studied EDCs included bisphenol A (BPA), its analogs (such as bisphenol S, BPS), phthalates, parabens, per- and polyfluoroalkyl substances (PFAS), and persistent organic pollutants (POPs). The review found consistent associations between EDC exposure and multiple reproductive endpoints, such as impaired semen quality, decreased ovarian reserve, infertility, polycystic ovary syndrome (PCOS), altered hormone levels—specifically estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)—and adverse outcomes in assisted reproductive technologies (ART), including in vitro fertilization (IVF). Despite methodological heterogeneity, the findings support the biological plausibility of EDCs in disrupting reproductive function. The review highlights the urgent need for regulatory measures, increased public awareness, and longitudinal studies to assess the cumulative effects of chronic EDC exposure on human fertility. Full article

It is a popular assumption that people learn certain practices for handling media in the course of their adolescence and adulthood, which make it difficult for them to develop new patterns for the use of media at a later point in their lives. From this theoretical standpoint, it is a challenge for older people to learn how to handle new media and integrate them into their current living situation. Beyond theoretical assumptions, there has formerly been a lack of exploratory investigations pursuing the conditions under which older adults take up digital media with which they were previously not familiar and incorporate them into their daily lives. Between October 2023 and March 2024, 32 semi-standardised individual interviews were conducted with a group of people between 80 and 93 years of age, who had recently acquired a digital medium and integrated it into their everyday lives. The decisive factor here was the presence of certain motives that generate plausible incentives to make permanent use of new media. The interviewees have purposefully acquired new media. It is notable that acquisition processes were strongly initiated by significant changes in life circumstances. In the case of most interviewees, the intention to acquire an internet-enabled medium was based on the wish to use a few selected functions. New options for online use were only explored after a while. The following patterns were identified regarding the motives and gratifications of acquisition: new media as…(1) hobby extension, (2) support network, (3) compensation tool, (4) connection opportunity, (5) escape from everyday life. It can be assumed that older people experience the use of new media as purposeful if they have specific motives for doing so. Biological, psychological and social correlations as well as ways of coping and dealing with age(ing) are relevant here. If daily use potentials are perceived as beneficial, older people show a high level of adaptability in terms of new media. Against this background, a gratification-orientated model appears to be a promising starting point for explaining the prerequisites for media adoption based on motives that generate plausible incentives for learning how to use new media at an older age. Full article

This paper introduces a novel neuromorphic-inspired hyper-heuristic framework (NeuHH) for solving the Capacitated Single-Allocation p-Hub Location Routing Problem (CSAp-HLRP), a challenging combinatorial optimization problem that jointly addresses hub location decisions, capacity constraints, and vehicle routing. The proposed framework employs Spiking Neural Networks (SNNs) as the decision-making core, leveraging their temporal dynamics and spike-timing-dependent plasticity (STDP) to guide the real-time selection and adaptation of low-level heuristics. Unlike conventional learning-based hyper-heuristics, NeuHH provides biologically plausible, event-driven learning with improved scalability and interpretability. Experimental results on benchmark instances demonstrate that NeuHH outperforms classical metaheuristics, Lagrangian relaxation methods, and reinforcement learning-based hyper-heuristics. Specifically, NeuHH achieves superior performance in total cost minimization (up to 13.6% reduction), load balance improvement (achieving a load balance factor of as low as 1.04), and heuristic adaptability (reflected by higher heuristic switching frequency). These results highlight the framework’s potential for real-time and energy-efficient logistics optimization in large-scale dynamic networks. Full article

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in a multitude of biological processes. However, their functional basis, particularly structure-based functional characteristics, remains elusive. lncRNAs exert their influence primarily through intricate interactions with various cellular components. Among these, interactions with proteins have garnered increasing attention. Recent research highlights the significance of the interactions with proteins as a plausible mechanism underlying lncRNA functions. Here, we delve into the interactions between lncRNAs and RNA-binding proteins (RBPs), explore their implications in cellular processes, and examine bioinformatic and experimental approaches for characterizing these interactions. We introduce an innovative ISD strategy to decipher the mysterious mechanism of lncRNAs. Through reviewing the recent advances in the study of proteins and their complexes, we incorporate the ISD strategy into our integrated structural analysis pipeline for comprehensively understanding the structure-function relationship of lncRNAs. Advances in the development of innovative therapeutic approaches based on lncRNA-protein interactions (LPIs) are reviewed accordingly. Full article

Objectives: Contrast-induced acute kidney injury (CI-AKI) remains a frequent and serious complication after cardiac catheterization. Sirtuin-1 (SIRT1), a NAD+-dependent deacetylase, plays a central role in renal protection against ischemia-reperfusion injury, inflammation, and vascular dysfunction. We aimed to investigate whether serum SIRT1 levels could serve as an early diagnostic biomarker for CI-AKI. Methods: This prospective case-control study included 50 patients undergoing elective percutaneous coronary intervention (PCI) for stable angina. Serum SIRT1 levels were measured at baseline, 24 h, and 72 h post-PCI. The occurrence of CI-AKI was defined by a standard rise in serum creatinine, and patients were stratified accordingly. Results: Although SIRT1 levels tended to be lower in patients who developed CI-AKI (n = 17) compared to those without (n = 33), the differences were not statistically significant at any time point (p > 0.05). However, a significant between-group difference was observed in the 72-h change in SIRT1 levels (Δ0–72 h, p = 0.037), with a greater decline in the CI-AKI group. Multivariable logistic regression also revealed a trend-level inverse association between 72-h SIRT1 levels and CI-AKI (β = −0.536, p = 0.099). Conclusions: While SIRT1 is biologically plausible as a renal protective factor, our findings suggest that serial SIRT1 measurement may offer added value as a dynamic biomarker rather than a static diagnostic tool. Confirmatory trials incorporating serial SIRT1 measurements may help translate this molecular signal into clinically actionable tools for early detection of CI-AKI. Full article

Equilibrium Propagation (EP) offers a biologically inspired alternative to backpropagation for training recurrent neural networks, but its reliance on symmetric feedback connections and stability limitations hinders practical adoption. The DirEcted EP (DEEP) model relaxes the symmetry constraint, yet suffers from convergence issues and lacks a principled learning guarantee. In this work, we generalize DEEP by incorporating neuronal leakage, providing new convergence criteria for the network’s dynamics. We additionally propose a novel local learning rule closely linked to the objective function’s gradient and establish sufficient conditions for reliable learning in small networks. Our results resolve longstanding stability challenges and bring energy-based learning models closer to biologically plausible and provably effective neural computation. Full article