Search Results (2,273)

Deep coal rocks exhibit strong time-dependent behavior, including significant plastic deformation and large tunnel displacements, which complicate tunnel support in deep underground engineering. A fractional creep model considering strong time-dependence was developed based on the classical Nishihara framework to capture this behavior. Additional time-dependent strains induced by stress-state variations were considered, with long-term rock strength adopted as the damage stress threshold. The stress difference between nominal and post-damage stress, ${\sigma }_D\left(t\right)$, defined as the stress gradient, was applied to a viscoelastic–plastic body containing a fractional Abel dashpot, producing conventional creep strain and strong time-dependent strain. The model was extended from one-dimensional to three-dimensional under triaxial stress conditions. The validity of the model was verified using triaxial creep test data for argillaceous sandstone and coal in deep roadways, and the model parameters were determined. The results demonstrate that the model accurately reproduces the full creep process, particularly the nonlinear accelerated stage influenced by strong time-dependence. Through stress-gradient-induced variations in strong time-dependent strain, the proposed creep model elucidates the progression of deformation in the strong time-dependent stage, offering a theoretical framework for the quantitative assessment of deep rock’s strong time-dependence. Sensitivity analysis identified the stress level, fractional order, and strong time-dependence coefficient $\alpha$ as key factors affecting strong time-dependent creep behavior. These findings indicate that tunnel support structures in deep environments are prone to instability, underscoring the necessity of accounting for strong time-dependence to ensure long-term stability. Full article

Background: Monkeypox (Mpox) is a re-emerging zoonotic disease caused by the monkeypox virus (MPXV). Transmission occurs primarily through direct contact with lesions or contaminated materials, with sexual transmission playing a significant role in recent outbreaks. In 2022, Mpox triggered a major global outbreak and was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), prompting renewed interest in effective control strategies. Methods: This study developed a compartmental SEIR-based model to assess the epidemiological impact of key interventions, including vaccination and isolation, while incorporating critical epidemiological parameters. Sensitivity analyses were conducted to examine (1) disease dynamics in relation to the basic reproduction number, and (2) how different parameters influence the curve of symptomatic infections. Real-world continental-scale data were used to validate the model and identify the parameters that most significantly affect epidemic progression and potential control of Mpox. Results: Results showed that the basic reproduction number was most influenced by the recovery rate, vaccination rate, vaccine effectiveness, and transmission rates of symptomatic and asymptomatic individuals. In contrast, the progression of symptomatic cases was highly sensitive to the case fatality rate and incubation rate. Conclusions: These findings highlight the importance of integrated public health strategies combining vaccination, isolation, and early transmission control to mitigate future Mpox outbreaks. Full article

Multiple myeloma is a clonal plasma cell malignancy with a highly variable range of clinical manifestations. Over recent decades, substantial progress has been made in laboratory diagnostics, which has deepened our understanding of disease biology, improved risk stratification, and informed treatment strategies. In an era of transformation and innovation, conventional laboratory methods remain essential, as cutting-edge technologies might not be immediately accessible to all laboratories. Nonetheless, even widely used laboratory methodologies present many challenges, such as variability in assay performance, interpretative criteria, and standardization. This review by the Portuguese Multiple Myeloma Group of the Portuguese Society of Hematology provides a comprehensive overview and practical appraisal of current conventional laboratory methods employed for multiple myeloma diagnosis. Full article

The NewEcoSmart project addresses the need to foster inclusive green and digital transitions in rural habitat sectors by systematically assessing local socio-technical readiness and tailoring capacity-building interventions. We adapted the validated SCIROCCO Exchange Maturity Self-Assessment Tool—selecting eight dimensions relevant to environmental, technological and social innovation—and conducted a two-phase evaluation across three pilot sites in Italy, Portugal and Spain. Phase 1 mapped stakeholder evidence against predefined criteria; Phase 2 engaged local actors (45+ adults, SMEs and micro-firms) in a self-assessment to determine digital, green and entrepreneurial skill gaps. For each domain of the SCIROCCO Tool, local actors can assign a minimum of 0 to a maximum of 5. The final score of the SCIROCCO tool can be a minimum of 0 to a maximum of 40. Quantitative maturity scores revealed heterogeneous profiles (Pacentro and Majella Madre = 5; Yecla = 10; Adelo Area = 23), underscoring diverse ecosystem strengths and limitations. A qualitative analysis, framed by Smart Healthy Age-Friendly Environments (SHAFE) domains, identified emergent training needs that are clustered at three levels: MACRO (community-wide awareness and engagement), MESO (decision-maker capacity for strategic planning and governance) and MICRO (industry-specific practical skills). The adapted SCIROCCO tool effectively proposes the assessment of socio-technical maturity in rural contexts and guides the design of a modular, multi-layered training framework. These findings support the need for scalable deployment of interventions that are targeted to the maturity of the local ecosystems to accelerate innovations through equitable green and digital transformations in complex socio-cultural settings. Full article

The automotive industry utilizes high-strength low-alloy (HSLA) steels and advanced high-strength steels (AHSS) to manufacture various components, including front and rear rails, chassis, and roll bars, among others. In countries where de-icing salts are used, these steels are exposed to a localized corrosive environment. This research aims to characterize the corrosion behavior of AHSS [dual-phase (DP), ferrite–bainite (FB), and complex-phase (CP)] using electrochemical techniques such as cyclic potentiodynamic polarization (CPP) curves and electrochemical noise (EN), by immersing the steels in NaCl, CaCl₂, and MgCl₂ solutions. Optical microscopy (OM) is used to observe the microstructure of the tested samples. The CPP corrosion behavior of AHSS exposed to chloride solutions exhibits corrosion densities in the range of 10⁻² and 10⁻³ mA/cm². The results generally indicated that AHSS are susceptible to localized corrosion due to the presence of positive hysteresis in the CPP. Zn results show that DP780 presented higher corrosion resistance, with 845 Ω·cm², whereas FB780 presented 253 Ω·cm² when exposed to NaCl. Additionally, the type of corrosion is localized. Full article

Anti-PD-1 therapies have transformed cancer treatment by restoring antitumor T cell activity. Despite their broad clinical use, variability in treatment response and immune-related adverse events underscore the need for therapeutic optimization. This article provides an integrative overview of the pharmacokinetics (PKs) of anti-PD-1 antibodies—such as nivolumab, pembrolizumab, and cemiplimab—and examines pharmacokinetic–pharmacodynamic (PK-PD) relationships, highlighting the impact of clearance variability on drug exposure, efficacy, and safety. Baseline clearance and its reduction during therapy, together with interindividual variability, emerge as important dynamic biomarkers with potential applicability across different cancer types for guiding individualized dosing strategies. The review also discusses established biomarkers for anti-PD-1 therapies, including tumor PD-L1 expression and immune cell signatures, and their relevance for patient stratification. The evidence supports a shift from traditional weight-based dosing toward adaptive dosing and therapeutic drug monitoring (TDM), especially in long-term responders and cost-containment contexts. Notably, the inclusion of clearance-based biomarkers—such as baseline clearance and its reduction—into therapeutic models represents a key step toward individualized, dynamic immunotherapy. In conclusion, optimizing anti-PD-1 therapy through PK-PD insights and biomarker integration holds promise for improving outcomes and reducing toxicity. Future research should focus on validating PK-based approaches and developing robust algorithms (machine learning models incorporating clearance, tumor burden, and other validated biomarkers) for tailored cancer treatment. Full article

Cervical cancer (CC) is the fourth most common cancer among women globally, with venous thromboembolism (VTE) representing a life-threatening complication. Cancer-associated thrombosis (CAT) arises from tumor-driven activation of hemostasis, worsening prognosis. Recently, circulating microRNAs (miRNAs) have emerged as potential biomarkers for both CAT and cervical tumorigenesis. Thus, this study aimed to assess the implications of five miRNAs—miR-20a-5p, -23a-3p, -125b-5p, -145-5p, and -616-3p—in CC-related VTE context. These miRNAs were quantified by RT-qPCR in plasma from 69 CC patients before treatment. Briefly, VTE occurred in nine patients, decreasing overall survival (OS) [log-rank test, p = 0.005; hazard ratio (HR) = 4.78; 95% confidence interval (CI), 1.42–16.05]. Lower miR-20a-5p levels predicted VTE (ꭓ² test, p = 0.027) and, in subgroup analyses, they were linked to cervical squamous cell carcinoma (CSCC) and older age (ꭓ² test, p = 0.003 and p = 0.043, respectively). In VTE patients, miR-145-5p downregulation was associated with improved OS (log-rank test, p = 0.018), an effect also observed in the adenocarcinoma (ADC) subgroup (log-rank test, p = 0.039). The remaining miRNAs showed subtype-specific links to clinicopathological features and survival. These findings highlight the potential value of circulating miRNAs in thrombotic risk and prognosis assessment in CC. Full article

Obesity is an epidemic with myriad health effects, but little is understood regarding individual obese phenotypes and how they may respond to therapy. Epigenetic changes associated with obesity have been detected in blood, liver, pancreas, and adipose tissues. Previous work using human organoids found that dietary glucose hyperabsorption is a steadfast trait in cultures derived from some obese subjects, but detailed transcriptional or epigenomic features of the intestinal epithelia associated with this persistent phenotype are unknown. This study evaluated differentially expressed genes and relative chromatin accessibility in intestinal organoids established from donors classified as non-obese, obese, or obese hyperabsorptive by body mass index and glucose transport assays. Transcriptomic analysis indicated that obese hyperabsorptive subject organoids have significantly upregulated dietary nutrient absorption transcripts and downregulated type I interferon targets. Chromatin accessibility and transcription factor footprinting predicted that enhanced HNF4G binding may promote the obese hyperabsorption phenotype. Quantitative RT-PCR assessment in organoids representing a larger subject cohort suggested that intestinal epithelial expression of CUBN, GIP, SLC5A11, and SLC2A5 were highly correlated with hyperabsorption. Thus, the obese hyperabsorption phenotype was characterized by transcriptional changes that support increased nutrient uptake by intestinal epithelia, potentially driven by differentially accessible chromatin. Recognizing unique intestinal phenotypes in obesity provides a new perspective in considering therapeutic targets and options with which to manage the disease. Full article

Peripheral nerve injuries remain a major clinical problem, and cell-free therapies using stem cell-derived bioproducts have emerged as promising alternatives. This study evaluated the influence of neurogenic differentiation and passage number on the secretomic and exosomal profile of human dental pulp stem cells (hDPCSs). Conditioned media from undifferentiated and neurodifferentiated hDPSCs, and exosomes derived from undifferentiated hDPSCs at passages 4 and 7, were analyzed using multiplex immunoassays, RT-PCR, and scanning electron microscopy (SEM). Neurodifferentiated hDPSCs at early passages secreted higher levels of neurotrophic, angiogenic and immunomodulatory factors, including FGF-2, IL-6, IL-8, and PDGF-AA. Exosomes from early-passage undifferentiated cells showed a more abundant and relevant neuroregenerative mRNA cargo in comparison to the later passages. Both cell types and exosomes adhered to the Reaxon^® nerve guidance conduit, confirming the permissive nature of the materials regarding cells and cellular products, allowing adhesion and survival. Neurite outgrowth assays performed on neurodifferentiated hDPSCs confirmed functional neural behavior. In later passages, a decline in secretory and exosomal activity was noted. These results highlight the relevance of early-passage hDPSCs as a source of bioactive factors and support their application in cell-free approaches for peripheral nerve regeneration. Full article

Because of the increased prevalence of chronic diseases, older adults frequently take many medications. However, adhering to a medication treatment tends to be difficult. The lack of medication adherence can cause health problems or even patient death. This paper describes the methodology used in developing a mobile augmented reality (MAR) pill box. The proposal supports patients in adhering to their medication treatment. First, we explain the design and construction of the automatic pill box, which includes alarms and uses QR codes recognized by the MAR system to provide medication information. Then, we explain the development of the MAR system. We conducted a preliminary survey with 30 participants to assess the feasibility of the MAR app. One hundred older adults participated in the survey. After one week of using the proposal, each patient answered a survey regarding the proposal functionality. The results revealed that 88% of the participants strongly agree and 11% agree that the app is a support in adhering to medical treatment. Finally, we conducted a study to compare the time elapsed between the scheduled time for taking the medication and the time it was actually consumed. The results from 189 records showed that using the proposal, 63.5% of the patients take medication with a maximum delay of 4.5 min. The results also showed that the alarm always sounded at the scheduled time and that the QR code displayed always corresponded to the medication that had to be consumed. Full article

Arbitrary zones are commonly used to describe and monitor external load (EL) during training and competitions. However, in recent years, relative speed zones have gained interest as they allow a more detailed description of the demands of each individual player, with their benefits largely unknown. This study aimed to (i) identify differences in EL methodological approaches using arbitrary and relative running speed zones; (ii) examine the effect of the methodological approaches to identify fast and slow basketball players during competition and training; and (iii) determine the effect of the season stage on the methodological approaches. Twelve players from a Spanish fourth-division basketball team were observed for a full season of matches and training using inertial devices with ultra-wideband indoor tracking technology and micro-sensors. Relative velocity zones were based on the maximum velocity achieved during each match quarter and were retrospectively recalculated into four zones. A linear mixed model (LMM) compared fast and slow players based on speed profiles between arbitrary and relative thresholds and during each competition stage. All players surpassed peak speeds of 24 km·h⁻¹ during the season, exceeding typical values reported in elite basketball (20–24.5 km·h⁻¹). Arbitrary thresholds produced greater distances in high-speed running (Zones 3 and 4) and yielded lower values in low-speed activity (Zone 1), with differences of ~100 m and ~120–250 m, respectively (p < 0.001), particularly for fast-profile players. These discrepancies were consistent across most stages of the season, although relative zones better captured variations in Zone 1 across time. Training sessions also elicited +8.7% to +40.7% greater distances > 18 km·h⁻¹ compared to matches. The speed zone methodology substantially influenced EL estimates and affected how player EL was interpreted across time. Arbitrary and relative approaches offer unique applications, with coaches and sport scientists encouraged to be aware that using a one-size-fits-all approach may lead to misrepresentation of individual player demands, especially when tracking changes in performance or managing fatigue throughout a competitive season. Full article

The growth of greenhouse gas emissions, driven by the use of internal combustion engines (ICE), highlights the urgent need for sustainable solutions, particularly in the shipping sector. Non-invasive predictive maintenance using acoustic signal analysis has emerged as a promising strategy for fault diagnosis in ICEs. In this context, the present study proposes a hybrid Deep Learning (DL) model and provides a novel publicly available dataset containing real operational sound samples of ICEs, labeled across 12 distinct fault subclasses. The methodology encompassed dataset construction, signal preprocessing using log-mel spectrograms, and the evaluation of several Machine Learning (ML) and DL models. Among the evaluated architectures, the proposed hybrid model, BiGRUT (Bidirectional GRU + Transformer), achieved the best performance, with an accuracy of 97.3%. This architecture leverages the multi-attention capability of Transformers and the sequential memory strength of GRUs, enhancing robustness in complex fault scenarios such as combined and mechanical anomalies. The results demonstrate the superiority of DL models over traditional ML approaches in acoustic-based ICE fault detection. Furthermore, the dataset and hybrid model introduced in this study contribute toward the development of scalable real-time diagnostic systems for sustainable and intelligent maintenance in transportation systems. Full article

Rift Valley fever (RVF) is a re-emerging vector-borne zoonotic disease that causes outbreaks in humans and animals across Africa. To better understand RVF at human–animal interfaces, a prospective longitudinal survey of people, livestock, and mosquitoes was conducted from 2016 to 2018, in two regions of Tanzania, with distinct climatic zones (Iringa and Morogoro). Molecular and serological tools for testing (RT-qPCR and IgM/IgG ELISA) for RVF virus (RVFV) were used to assess infection and exposure in people and animals. Mosquitoes were collected quarterly from 10 sentinel locations. In total, 1385 acutely febrile humans, 4449 livestock, and 3463 mosquito pools were tested. In humans, IgM seroprevalence was 3.75% (n = 52/1385), and overall seroprevalence (IgM and/or IgG positive) was 8.30% (n = 115/1385). People from Iringa had a higher exposure risk than those from Morogoro (aOR 2.63), and livestock owners had an increased risk compared to non-owners (aOR 2.51). In livestock, IgM seroprevalence was 1.09%, while overall seroprevalence was 10.11%. A total of 68.4% of herds had at least one seropositive animal. Sentinel animal follow-up revealed that the probability of seroconversion was significantly higher in Morogoro. Low-level RVFV RNA was detected in 8 human and 22 mosquito pools. These findings indicate active transmission among vectors, livestock, and people during the study period, highlighting the need for One Health surveillance approaches for RVFV and other arboviruses. Full article

Camellia oleifera Abel shell is an abundant lignocellulosic byproduct of the Chinese woody oil industry, which is currently underutilized. To achieve its high-value utilization, this study developed an innovative cascade process integrating ultrasound-assisted extraction and macroporous resin purification for the efficient preparation of purified polyphenols from the shell (P-CPCS). The major constituents were identified by quadrupole/Orbitrap high-resolution mass spectrometry (HPLC-Q-Exactive-MS: Biotech Pack Co., Ltd., Beijing, China) analysis. The optimized process significantly enhanced the polyphenol yield (40.05 ± 0.58 mg GAE/g dw) and purity (57.72%), surpassing conventional methods. P-CPCS exhibited exceptional multifunctional bioactivities, including potent antioxidant capacity (with low IC₅₀ values against DPPH, ABTS⁺·, and ·OH radicals), effective tyrosinase inhibition (whitening effect), and significant bacteriostatic effects against various pathogens. Furthermore, P-CPCS notably suppressed the LPS-induced inflammatory response in RAW264.7 macrophages by reducing NO overproduction. This work highlights a novel and efficient strategy for upcycling agricultural waste into a high-performance natural antioxidant, positioning P-CPCS as a promising ingredient for applications in functional foods, cosmetics, and biomaterial stabilization. Full article

Algal biorefineries constitute an emerging platform for the sustainable production of renewable bioproducts; however, their economic viability remains constrained by the high costs associated with microalgal cultivation and biomass harvesting. This study investigated an integrated strategy combining macronutrient optimization with electrocoagulation–flocculation (ECF) harvesting for Chlorella vulgaris. A Central Composite Design (CCD) was employed to optimize concentrations of NaNO₃, KH₂PO₄, and MgSO₄ with the dual objective of maximizing biomass yield and enhancing biocompound content. Subsequently, the ECF process parameters—current density, electrolysis duration, pH, and electrolyte concentration—were optimized to improve harvesting efficiency. Under the optimal macronutrient conditions (NaNO₃: 100.00 mg/L; KH₂PO₄: 222.12 mg/L; MgSO₄: 100.84 mg/L), the model predicted a maximum biomass concentration of 0.475 g/L, along with 32.79% w/w carbohydrates and 6.79 mg/L chlorophyll-a. Optimal ECF harvesting conditions (current: 0.57 A; pH: 4.00; electrolysis time: 12.70 min; electrolyte: 1.74 g/L) achieved a biomass recovery efficiency of 89.51% w/v. These results demonstrate that coupling nutrient optimization with ECF-based harvesting offers a synergistic, scalable, and cost-effective pathway to improve the sustainability of algal biorefineries. Full article