Search Results (321)

Developing potent adjuvants is critical for enhancing vaccine efficacy, particularly for subunit antigens. Background/Objectives: This study evaluates a novel composite adjuvant system combining liposomal QS-21 and CpG ODNs to enhance vaccine-induced immunogenicity, particularly Th1-type cellular immunity. Methods: To mitigate QS-21’s hemolytic toxicity and ensure precision delivery, a stable liposomal formulation was developed. Mice models were established using varicella-zoster virus (VZV) glycoprotein E (gE) or ovalbumin (OVA) as antigens to evaluate humoral and cellular immune responses. Results: Immunization with gE protein formulated with this novel adjuvant synergistically triggered robust immune responses, outperforming single adjuvants and the combination of QS-21/MPL. Across broad dose ranges, it induced higher Th1-type cellular immunity and comparable humoral immunity relative to AS01_B. Mechanistic studies revealed that the adjuvant significantly enhances the recruitment of dendritic cells (DCs), monocytes, and neutrophils to draining lymph nodes (dLNs) while upregulating co-stimulatory molecules CD40 and CD86 on DCs. Furthermore, the formulation triggered robust, transient increases in Th1-associated cytokines (IFN-γ, IL-12) and chemokines (CXCL9, CXCL10) across the injection site, serum, and dLNs. Conclusions: These findings indicate that the liposomal QS-21 and CpG ODNs system is a highly effective platform for promoting robust Th1-biased immunity, offering a promising adjuvant candidate and a solid experimental foundation for developing next-generation vaccines requiring potent cellular immunity. Full article

Additive manufacturing (AM) monitoring is fundamentally constrained by the severe scarcity of annotated data for layer-wise segmentation. This paper addresses this bottleneck by introducing a scalable, high-fidelity synthetic data generation pipeline built on the Slice-100K dataset, capable of producing large volumes of layer-wise semantic segmentation masks. Through analysis of this large-scale synthetic data, we identify a systemic foreground–background class imbalance (1:24 ratio) inherent to AM monitoring, which causes standard Dice loss formulations to diverge catastrophically into a phenomenon we formalize as the “Dice Crash.” To effectively leverage large amounts of unlabeled data, we adapt the Meta Pseudo-Labeling (MPL) framework for industrial segmentation. We evaluate MPL’s true marginal utility by integrating it with both a standard U-Net and a robust state-of-the-art nnU-Net architecture. Experimental outputs show that while MPL yields substantial performance gains (+15.2%) on weak baselines, integrating it with an optimally configured strong baseline consistently improves segmentation accuracy and suppresses false foreground detections, thereby mitigating confirmation bias. These findings demonstrate that semi-supervised learning via continuous bilevel optimization offers a practical and robust enhancement to data-scarce additive manufacturing monitoring. Because any hidden defects in the topmost layer will be permanently buried by subsequent extrusion, this foundational layer-wise segmentation step is the most critical primitive of the monitoring pipeline. Full article

Abnormal tarsal posture in dogs may be associated with structural lesions such as common calcaneal tendon complex rupture, plantar-supporting structure injury, tarsocrural instability, or neurologic dysfunction; however, common calcaneal tendon rupture is typically associated with a plantigrade posture rather than the weight-bearing-dependent tarsal hyperextension pattern described in this case. A 3-year-old intact male Pomeranian developed bilateral weight-bearing-dependent tarsal hyperextension immediately after bilateral medial patellar luxation (MPL) surgery performed at another hospital. At our hospital, complete cranial cruciate ligament rupture of the right stifle and recurrent grade II MPL of the left stifle were identified. Right lateral fabellotibial suture stabilization using a LigaFiba^® 75 lateral suture and crimp system, with supportive reapplication of a 0.8 mm Kirschner wire at the previous tibial tuberosity transposition site, and left trochlear block recession with capsular resection and imbrication were performed. No direct surgical treatment of either tarsus was undertaken. During follow-up after stifle stabilization, bilateral tarsal hyperextension progressively decreased and was no longer clinically observed by 5 months. This case suggests that bilateral weight-bearing-dependent tarsal hyperextension may occur secondary to proximal stifle pathology even in the absence of major structural tarsal instability, and that hyperextension may resolve clinically following stifle stabilization. Full article

The fuel-cell (FC) technology currently being considered to reduce aircraft greenhouse gas emissions may require large and heavy cooling systems. The paper introduces the two-phase (2$\mathsf{\Phi }$) Mechanically Pumped Loop (MPL) for FC cooling and compares it numerically with the conventional Ethylene Glycol Water (EGW) single-phase (1$\mathsf{\Phi }$) cooling system for a $1.2$ MW heat-dissipation load. Considering an operating temperature of 90 °C, the system mass of the 2$\mathsf{\Phi }$ MPL with and without an accumulator is found to be, respectively, 33% and 64% lower than the EGW system. Furthermore, the frontal area of the ram air heat exchanger (HX) was found to be 19% smaller, reducing ram air drag. An increase of the operating temperature to 130 °C was found to reduce the cooling system mass by 21% for the 1$\mathsf{\Phi }$ MPL, and 22 to 29% for the 2$\mathsf{\Phi }$ MPL. The frontal area of the ram air HX was found to be reduced by 44% and 40% for the 1$\mathsf{\Phi }$ and 2$\mathsf{\Phi }$ MPL, respectively. These results demonstrate the considerable performance gain of the 2$\mathsf{\Phi }$ MPL over the 1$\mathsf{\Phi }$ MPL for FC cooling, and the benefits of increasing the operating temperature for the cooling system. Full article

This paper presents a Digital Twin (DT)-based framework for the control, monitoring, and intelligent optimization of an Assembly/Disassembly/Repair Mechatronic Production Line (A/D/R MPL), developed as a laboratory platform aligned with Industry/Education 4.0/5.0 paradigms. The A/D/R MPL is assisted by two complementary cyber–physical robotic systems: an Assembly/Disassembly/Replacement Cyber–Physical Robotic System (A/D/R CPRS), and a Mobile Cyber–Physical Robotic System (MCPRS), enabling both fixed and mobile intelligent operations. The CPRS is equipped with an industrial robotic manipulator (IRM) responsible for A/D/R tasks, while the A/D Mechatronic Line (A/D ML) consists of seven interconnected workstations (WS1–WS7) dedicated to storage, transport, quality control, and final product handling. MCPRS includes a wheeled mobile robot (WMR), carrying a robotic manipulator (RM) and Mobile Visual Servoing System (MVSS). Each workstation is connected to a local slave programmable logic controller (PLC), which communicates via PROFIBUS with a master PLC located at the CPRS level. Additional communication infrastructures include LAN PROFINET and LAN Ethernet for local integration, and WAN Ethernet connectivity enabled through open platform Communication-Unified Architecture (OPC-UA), ensuring interoperability, scalability, and remote accessibility. Also, MODBUS TCP as serial industrial communication is used between the master PLC and the MCPRS. Virtual environment supports task planning through Augmented Reality (AR) and real-time monitoring through Virtual Reality (VR). The system behaviour is modelled with synchronized hybrid Petri Nets (SHPNs) which describe the discrete and hybrid dynamics of A/D/R processes. Artificial intelligence (AI) techniques are integrated into the DT framework for optimal task scheduling and adaptive decision-making. As a laboratory-scale implementation, the proposed system provides a comprehensive platform for experimentation, validation, and education. It supports Education 4.0/5.0 objectives by facilitating hands-on learning, human–machine interaction, and the integration of emerging technologies such as AI, Digital Twins, AR/VR, and cyber–physical systems. At the same time, it embodies Industry 4.0/5.0 principles, including interoperability, decentralization, sustainability, robustness, and human-centric design. Full article

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal hematopoietic dysregulation, amplification of chronic inflammation, and progressive remodeling of the bone marrow fibrotic niche, clinically manifesting as bone marrow failure, splenomegaly, and systemic inflammatory symptoms. Although Janus kinase (JAK) inhibitors can alleviate symptom burden and reduce spleen size, they have limited capacity to eradicate malignant clones or reverse fibrosis. Allogeneic hematopoietic stem cell transplantation remains the only potentially curative option; however, its application is constrained by advanced age, comorbidities, unavailable donor, and transplant-related risks. Therefore, the development of disease-modifying therapeutic strategies has become a central focus in MF research. Chimeric antigen receptor T (CAR-T)-cell therapy has demonstrated robust efficacy across various hematologic malignancies. Its application in MF holds the potential not only to selectively eliminate malignant hematopoietic clones but also to modulate the immunosuppressive and profibrotic microenvironment through advanced cellular engineering, thereby enabling a dual therapeutic paradigm involving both clonal control and microenvironmental reprogramming. In this context, potential targets and pathways include CD123, myeloproliferative leukemia protein (MPL), fibroblast activation protein (FAP), the TGF-β signaling axis, the CXCR4–CXCL12 niche-regulatory axis, and molecules associated with myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Future strategies may optimize both efficacy and safety through combinatorial approaches, including integration with JAK inhibitors, development of armored CAR-T constructs, and bridging to hematopoietic stem cell transplantation. Collectively, CAR-T-cell therapy offers a promising avenue for shifting MF management from symptomatic control toward true disease modification. Full article

Bovine milk is a primary dietary source of nutrients and bioactive compounds. However, its safety is increasingly under threat due to contamination from mining and intensive agriculture. In the Peruvian Andes, where small-scale dairy farming coexists with historical environmental liabilities, identifying the transfer of metals into the food chain is essential for public health. This study quantifies the concentrations of lead (Pb) and cadmium (Cd) in raw milk from small-scale producers in rural districts in the province of Huancayo. Non-carcinogenic risks for populations aged 2–85 years were assessed under three consumption scenarios. Forty-five samples were analyzed using microwave plasma atomic emission spectrometry (MP-AES). The mean concentrations of Pb and Cd were 11.30 ± 18.94 µg/kg and 7.85 ± 18.11 µg/kg, respectively, which are below the maximum permissible limits (MPL). However, spatial analysis identified critical hotspots near smelters, where Pb levels reached 103 µg/kg, which is a significant exceedance of the MPL of 20 µg/kg. Toxicological modelling showed that the Hazard Index (HI) remained below the unity threshold (HI < 1) for all scenarios, ruling out immediate systemic risks. Nevertheless, the highest HI (0.78) was observed in two-year-old children in the high-consumption scenario, highlighting a localized neurodevelopmental concern. These findings emphasize the importance of georeferenced environmental monitoring and differentiated public health policies to mitigate the chronic low-level exposure to metals in vulnerable, high-altitude populations. Full article

The microporous layer (MPL) is a key functional component in proton exchange membrane fuel cells (PEMFCs), and clarifying the quantitative relationship between its microstructure and mass transport properties is essential for improving cell performance. In this study, a three-dimensional MPL model was developed using a stochastic reconstruction method, and, together with a random walk algorithm, was employed to systematically investigate the effects of porosity, carbon sphere radius, maximum overlap ratio, seed ratio, and polytetrafluoroethylene (PTFE) content on permeability, effective diffusivity, and tortuosity. The results reveal that increasing porosity reduces tortuosity from 1.7 to 1.3, while permeability and effective diffusivity increase by factors of approximately 6.5 and 1.8, respectively. As the carbon sphere radius increases, tortuosity decreases from 1.55 to 1.35, accompanied by an increase in permeability from 2 × 10⁻¹⁶ m² to 20 × 10⁻¹⁶ m². Moreover, increasing the PTFE content raises permeability from 5 × 10⁻¹⁶ m² to 22.5 × 10⁻¹⁶ m², corresponding to an enhancement by a factor of approximately 4.5. The high-accuracy fitting equations obtained from the simulation results provide theoretical guidance for the microstructural design and optimization of MPLs, which can enhance oxygen transport and water management, reduce mass transport losses, and thereby benefit high-power-density operation and the overall efficiency of PEM fuel cells. Full article

This study investigates the determinants of borrower repayment intentions in Marketplace Lending (MPL) platforms, focusing on the interplay between behavioural factors and Environmental, Social, and Governance (ESG) awareness in the Hungarian context. A Partial Least Squares Structural Equation Modelling (PLS-SEM) approach was employed to analyze survey responses from 477 participants familiar with MPL platforms. The study integrates constructs from behavioural finance (Perceived Usefulness, Perceived Ease of Borrowing, Theory of Planned Behaviour) and ESG-related factors (Socially Responsible Investment Theory, Reciprocity Theory) to assess their influence on repayment intentions. Perceived Usefulness (PU) emerged as the strongest predictor of Repayment Intention (RI) (β = 0.554, p < 0.001), highlighting the importance of platform functionality. Socially Responsible Investment Theory (SRIT) also had a significant positive impact (β = 0.194, p < 0.01), suggesting that ethical lending practices enhance borrower accountability through reciprocity mechanisms. Conversely, Continuance Intention to Borrow (CIB) and Credit Risk Theory (CRT) showed no significant effects. This study contributes to the literature by bridging behavioural finance, credit risk theory, and ESG principles in FinTech lending, offering a novel framework for sustainable lending practices. Full article

This project investigates how the orientation of the carbon cathode with a single-sided microporous layer (MPL) affects battery performance through electrochemical tests, neutron tomography, and titration experiments. The titration experiment quantitatively assesses the amount of solid product (Li₂O₂) deposited on the electrode surface. In addition, neutron imaging with a 16 µm voxel resolution provides details on the spatial distribution of the solid product within the porous electrodes. Additionally, the performance impact of two electrolyte solvents, tetra ethylene glycol dimethyl ether (TEGDME) and dimethyl sulfoxide (DMSO), is evaluated when used to soak the carbon cathode. The cathode orientation where the MPL faces toward the electrolyte and separator reaches higher discharge and charge capacities and greater average discharge voltages compared to when the MPL faces away from the separator. Batteries discharged with DMSO as the solvent have a 64.86% decrease on average in discharge capacity compared to batteries using TEGDME as the solvent. Both the titration experiments and neutron imaging confirmed that the amount of solid products exhibits a linear correlation with the discharged capacity. Additionally, electrolytes with a high donor number, such as DMSO, were found to result in a smaller amount of Li₂O₂ deposited on the electrode surface. Full article

Background/Objectives: Adjuvants, added to vaccines to enhance immune responses, are central to shaping the magnitude and durability of immunity, yet their precise mechanisms remain incompletely defined. This study evaluated how diverse adjuvant combinations influence HPV vaccine immunogenicity in non-human primates, with a particular focus on impacts on hematopoietic biology—megakaryocytes and platelets—and broader innate and adaptive pathways. Methods: Eight adjuvanted formulations, each incorporating distinct immunomodulatory components and delivery platforms, were compared against an alum-only control in non-human primates. Longitudinal antibody titers (HPV16-specific) were measured up to 54 weeks, and blood transcriptomes were profiled at Day 1 and Day 7 after both prime and boost doses to assess pathway-level enrichment and gene-expression patterns. Results: Several adjuvant combinations significantly increased antibody titers at 54 weeks compared with alum alone. Formulations containing cationic lipid or monophosphoryl lipid A (MPL) were associated with enhanced antibody responses. Early upregulation of immune-related genes across innate and adaptive pathways was also observed, with some combinations (e.g., inclusion of QS21 or ISCOMs) showing similar trends. Distinct group- and time-dependent transcriptional signatures were observed, with higher-responding formulations exhibiting stronger enrichment in pathogen-influenced signaling and cellular/humoral immune programs. Conclusions: Adjuvant selection and formulation strategy substantially modulate vaccine immunogenicity and early transcriptional programs, including innate, adaptive, and hematopoietic pathways. While individual adjuvants differentially regulate immune and platelet-associated genes, common pathway-level patterns emerge across formulations. These findings suggest candidate mechanisms for prolonged vaccine efficacy and provide actionable insights to guide rational adjuvant design for sustained immune protection. Full article

Aim of the study: To investigate the detection rate of respiratory viruses identified by multiplex real-time PCR (MPL real-time PCR) in respiratory specimens collected from hospitalized patients with acute lower respiratory tract infections (LRTI) over a five-year period (2020–2024), and to emphasize the importance of MPL real-time PCR testing in identifying respiratory viruses responsible for severe lower respiratory tract infections requiring hospitalization. Subjects and Methods: This cross-sectional retrospective study analyzed 15,936 respiratory specimens collected from hospitalized patients between 2020 and 2024. Seventeen respiratory viruses were detected using MPL real-time PCR. Statistical comparisons were performed using the chi-square test. Results and Discussion: The overall respiratory virus detection rate was 31.88% and was significantly higher in children than in adults (52.98% vs. 18.10%). The most frequently detected viruses were rhinovirus, influenza A, respiratory syncytial virus, and parainfluenza virus type 3, while influenza A and SARS-CoV-2 predominated in adults. During the peak of the COVID-19 pandemic in 2021, SARS-CoV-2 accounted for 78.92% of detected viruses, accompanied by marked suppression of other respiratory pathogens. Measles virus re-emerged in 2024, predominantly affecting children (17.65%). Most Respiratory virus-positive cases (82.8%) involved single-agent infections. Conclusions: Hospitalized acute LRTI cases often lack distinctive clinical signs to identify viral pathogens. MPL real-time PCR provides simultaneous multi-virus detection, enabling accurate etiological diagnosis and strengthening hospital-based viral surveillance, particularly in resource-limited settings. Full article

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases originating from hematopoietic stem cell transformation, characterized by the clonal proliferation of hematopoietic progenitors. A specific subset includes myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions, particularly involving PDGFR A or B, which are sensitive to TK inhibitor treatment. We report a case of a 21-year-old patient with a myeloproliferative/myelodysplastic neoplasm, presenting with hyperleukocytosis, anemia, thrombocytopenia, and elevated LDH. The peripheral blood smear showed hypogranular neutrophils, eosinophils, basophils, and myeloid precursors. The absence of BCR::ABL1 and mutations in JAK2, CALR, and MPL excluded common MPNs. Cytogenetic analysis revealed a rearrangement between chromosomes 5 and 14. FISH analysis confirmed an inverted insertion from chromosome 5 to chromosome 14, involving the PDGFRB gene. WGS and RNAseq identified a fusion between PDGFRB and CCDC88C, causing the constitutive activation of PDGFRB. The fusion gene was confirmed by sequencing. This allowed for targeted therapy with a tyrosine kinase inhibitor (TKI), leading to molecular remission monitored by RT-qPCR. This case highlights how a multidisciplinary approach can identify atypical transcripts in MPN, guiding targeted therapy with TK inhibitors, thus resulting in effective treatment and molecular remission. Full article

Varicella-zoster virus (VZV) is a human neurotropic herpesvirus. The primary infection with VZV causes chickenpox and establishes latency in sensory and dorsal root ganglia. Viral reactivation leads to herpes zoster (HZ), which is accompanied by complications such as postherpetic neuralgia (PHN), causing a significant disease burden. At present, vaccination is the most effective preventive measure. We developed a recombinant zoster vaccine, gE/BFA01, which comprises truncated VZV glycoprotein E and the liposome-based adjuvant BFA01 (containing MPL and QS-21). In this study, we evaluated the recombinant zoster vaccine’s immunogenicity in a live attenuated VZV-primed C57BL/6N mouse model and explored the mechanism of action of the BFA01 adjuvant. The results indicate that the gE/BFA01 vaccine induces superior antibody responses and stronger cellular immune responses compared with gE with aluminum hydroxide. Furthermore, gE/BFA01 showed comparable immunogenicity to the licensed vaccine Shingrix. Mechanistic investigations revealed that the BFA01 adjuvant can enhance the recruitment of innate immune cells at the injection site, increase the expression of DCs surface maturation markers, and activate multiple inflammatory signaling pathways in lymph nodes. Collectively, these findings indicate that gE/BFA01 can induce potent humoral and cellular responses, supporting its further development as a high-efficiency vaccine candidate. Full article

Primary myelofibrosis (PMF) is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm (MPN) that features clonal proliferation of atypical megakaryocytes and myeloid cells, fibrosis of the bone marrow, extramedullary hematopoiesis, and increased risk of leukemic transformation to acute myeloid leukemia (AML). With the widespread application of molecular studies, especially next generation sequencing (NGS), significant advances have reshaped our understanding of the molecular pathogenesis of PMF and the prognostic relevance of specific gene mutations. In this review, we summarize its clinicopathologic features, genetic and molecular findings, updated diagnostic criteria, and differential diagnosis. These updates have been incorporated into the 5th edition of the World Health Organization classification of Hematolymphoid Tumors (WHO-5th) and the 2022 International Consensus Classification (ICC), thereby improving diagnostic accuracy and risk stratification, both of which are essential for tailoring treatment strategies and enhancing patient outcomes. Full article