ABSTRACT Pulmonary arterial hypertension (PAH) is a life‐threatening condition with no cure, making research into its underlying mechanisms critical. The platelet‐derived growth factor (PDGF) signaling pathway plays a crucial role in vascular remodeling, a key factor in PAH progression. Anti‐PDGF receptor therapies, such as imatinib, show promise but are associated with significant side effects. Recent research identified PDGF‐D as a new risk gene in idiopathic PAH, highlighting the need for further investigation into the PDGF pathway in the disease. In this study, we investigated PDGF‐D, a specific PDGFRβ ligand, as a potential therapeutic target. RNA‐Seq data from healthy lungs indicated that PDGF‐D is predominantly expressed in inflammatory cells, whereas in vascular lesions of idiopathic PAH patients, PDGF‐D was produced by various cell types. In vitro, PDGF‐D induced mitogenic effects on pulmonary arterial smooth muscle cells. However, genetic deletion of PDGF‐D in the chronic hypoxia mouse model of pulmonary hypertension showed no significant impact on vascular muscularization, hemodynamic parameters, or right ventricular hypertrophy. But, the absence of hypoxia‐induced Pdgfrb upregulation and the lack of increased expression of PAH‐regulated genes, Fgf2 and Notch3, in PDGF‐D‐deficient mice, suggests activation of alternative mechanisms. MicroRNA analyses revealed PDGF‐d‐related alterations in the expression of miR‐21 and miR‐451, both important regulators in PAH, further supporting the notion that PDGF‐D plays a unique role in PAH development. Taken together, our data suggest that PDGF‐D may target a distinct population of PDGFRβ‐expressing cells, separate from those stimulated by PDGF‐B, positioning PDGF‐D as a potentially unique and compelling therapeutic target for PAH.

This paper describes testing the solid particle erosion resistance of the composite based on A 356.0 aluminium alloy with the addition of 6 % fly ash (FA) as reinforcement. The composite samples were tested in the as-cast state and after being subjected to the multiple passes of the equal-channel angular extrusion (ECAE). The cast composite was obtained by compo-casting. This method implies the mixing of reinforcement into the semi-solid matrix. Extrusion was performed in 3 passes, with rotation around the longitudinal axis by 90° after each pass (route BC). Solid particle erosion resistance was determined based on volume loss ΔV. During the erosion test, the silicon carbide (SiC) particles were used as erodent. The impact angle of the particles was varied (30° and 90°). The results show that after each pass, the microstructure of the composite was improved and wear by solid particles was reduced.

Plywood is a wood-based material that, due to its good properties, has found applications in many areas of the wood industry, transport, and construction. Plywood is fabricated from multiple layers of veneer glued together with the grain direction of each layer of veneer perpendicular to that of the adjacent layers. In order to improve primarily mechanical properties, plywood is reinforced with various fibers, both natural and synthetic. Basalt is used in various forms as a material for reinforcing composite materials. Basalt mesh is primarily used in construction to improve the properties of wall and road structures. In order to determine the possibility of using basalt mesh in the production of wood-based composite materials, plywood reinforced with basalt mesh was produced in laboratory conditions. One, or two, or three basalt meshes were placed in different positions in the panel construction. The manufactured plywood reinforced with basal mesh was tested in accordance with EN 310. The paper presents the results of the bending strength test depending on the quantity and position of the basal mesh in the plywood construction.

Fire resistance of wood materials is crucial for the safety and longevity of construction structures, with spruce wood (Picea abies spp.) being widely used due to its mechanical properties. However, its natural fire resistance is limited, which poses a challenge in the context of fire safety. This study investigates the effects of various treatments and additives on enhancing the fire resistance of spruce wood. The methodology includes testing fire resistance using the small flame test in accordance with relevant standards. The expected results could contribute to improving safety standards in the construction industry, enabling broader and safer application of spruce wood in fire-sensitive constructions. Surface roughness analysis revealed significantly smoother surfaces in treated samples (Sa = 9.03 μm) compared to untreated sawn samples (Sa = 84.54 μm), which contributed to reduced combustion intensity. In small flame tests, untreated samples exhibited visible flames with flame heights up to 13.5 cm, whereas Burn Block treated samples showed no flame development and minimal color changes. Interestingly, burning depth was greater on treated samples, reflecting surface carbonization and the formation of a protective intumescent layer that slowed heat transfer and prevented deeper structural damage.

The research aims to improve the durability and functionality of traditional wooden structures through innovative technologies, reducing the ecological footprint and enhancing the economic viability of local materials. The model benches are made from five different types of indigenous conifer wood: Norway spruce, scots pine, larch, thermally modified spruce, and spruce treated with a copper-ethanolamine based biocide. Sensors installed on the benches allow continuous monitoring of wood moisture, a key factor in determining material durability under specific climatic conditions. Collected data will enable the evaluation of optimal wood types for various climatic conditions, promoting the wider use of indigenous, environmentally renewable materials. The project also aims to connect the wood protection industry with end-users, fostering sustainable approaches to environmental preservation, cultural landscapes, and wooden heritage. The research results support the application of wood materials in sectors such as agriculture, maritime transport, and tourism, contributing to ecologically sustainable and economically efficient use of natural resources.

Cutting processes, in general, and wood cutting processes in particular, are complex to explain and describe, depending on a number of influencing factors such as material characteristics, cutting tool geometry and cutting parameters. A thorough understanding of the characteristics of woodworking machining, such as cutting tool wear, cutting forces, energy consumption, and cutting tool stress, gives the opportunity to improve product quality, increase production efficiency, or improve the technological process. In this paper, some characteristic parameters of processing in flat, extensive milling of solid wood of different species are analysed in order to determine the significance of the selected parameters, as well as their mutual influences on the required cutting power.

Dynamic analysis can be used to determine dynamic displacements, time history, and the frequency content of loads. One of the analytical techniques for calculating the linear response of structures to dynamic loading is modal analysis. In modal analysis, the structural response is decomposed into several modes of oscillation. A mode is defined by its frequency and shape. Engineers refer to the mode with the lowest frequency (longest period) as the fundamental mode of oscillation. This paper presents Holzer’s approximate method for determining the modes and periods of oscillation for frame structures. The proposed approximation method, based on the relative stiffness of floors and the ground level, is also analyzed. The results obtained using the proposed approximate procedure do not significantly deviate from those obtained through more precise calculations. Therefore, it is emphasized that the method can be used both in practice and for verifying computer analyses of complex systems.

In this paper, a comparison between serverless databases and conventional data storage models is discussed, with a focus placed on architectural differences, performance measures, cost-benefit analysis, and use case applicability. In cloud-native applications, the use of serverless databases, in which resources are dynamically allocated as needed, is increasingly observed. In contrast, traditional databases require manual operations for infrastructure provisioning and maintenance. Situations in which serverless databases are preferable, as well as those where traditional approaches remain suitable, are characterized in this work. A guide for selecting a database system in modern computing environments is provided, based on an evaluation of systems such as AWS Aurora Serverless, Firebase, PostgreSQL, and MongoDB.

Pain remains one of the most burdensome symptoms in rheumatoid arthritis (RA), often persisting despite inflammatory remission and profoundly impairing quality of life. This review aimed to evaluate the clinical efficacy and mechanistic pathways by which Janus kinase (JAK) inhibitors alleviate RA-related pain. Evidence from randomized clinical trials demonstrates that JAK inhibitors have demonstrated rapid and significant pain relief, often exceeding that of methotrexate or biologic DMARDs. Improvements in patient-reported pain scores seem to typically emerge within 1–2 weeks and are sustained over time. Beyond anti-inflammatory effects, JAK inhibitors modulate central sensitization and nociceptive signaling by attenuating IL-6 and GM-CSF activity, reducing astrocyte and microglial activation, and downregulating nociceptor excitability in dorsal root ganglia and spinal pathways. Preclinical models further suggest that JAK inhibition interrupts neuroimmune feedback loops critical to chronic pain maintenance. Comparative and network meta-analyses consistently position JAK inhibitors among the most effective agents for pain control in RA. However, individual variability in response, partly due to differential JAK-STAT activation and cytokine receptor uncoupling, underscores the need for biomarker-guided treatment approaches. JAK inhibitors represent a mechanistically distinct and clinically impactful class of therapies that target both inflammatory and non-inflammatory pain in RA. Their integration into personalized pain management strategies offers a promising path to address one of RA’s most persistent unmet needs.

Summary Background For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010–23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings Total numbers of global DALYs grew 6·1% (95% UI 4·0–8·1), from 2·64 billion (2·46–2·86) in 2010 to 2·80 billion (2·57–3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0–14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31–1·61) global DALYs in 2010, increasing to 1·80 billion (1·63–2·03) in 2023, alongside a concurrent 4·1% (1·9–6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176–209] DALYs), stroke (157 million [141–172]), and diabetes (90·2 million [75·2–107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0–107·5]), depressive disorders (26·3% [11·6–42·9]), and diabetes (14·9% [7·5–25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837–917) in 2010 to 681 million (642–736) in 2023, and a 25·8% (22·6–28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7–61·0) for diarrhoeal diseases, 42·9% (38·0–48·0) for HIV/AIDS, and 42·2% (23·6–56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6–22·0) and 24·8% (7·4–36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7–19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18–1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation—with high SBP accounting for 8·4% (6·9–10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories—behavioural, metabolic, and environmental and occupational—risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8–37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0–11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023—eg, declining by 54·4% (38·7–65·3) for unsafe sanitation, 50·5% (33·3–63·1) for unsafe water source, and 45·2% (25·6–72·0) for no access to handwashing facility, and by 44·9% (37·3–53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [–2·7 to 15·6]; non-significant). Interpretation Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors—eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG—including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic—the complex interaction of multiple health risks, social determinants, and systemic challenges—will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Funding Gates Foundation and Bloomberg Philanthropies.

Acinic cell carcinoma (ACC) of the breast is a very rare, primary salivary gland‐type breast malignancy, with ~100 reported cases in the literature. Limited information about the clinical features and outcomes of patients with ACC is available.

OBJECTIVES To compare the clinicopathologic features, treatment patterns, and survival outcomes of mucinous tubular and spindle cell carcinoma (MTSCC) with those of clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (PRCC). SUBJECTS AND METHODS This retrospective cohort study used SEER data from 1983 to 2022, including 461 MTSCC, 133,229 ccRCC, and 29,442 PRCC cases. Demographic, clinical, and treatment variables were analyzed using chi-square, ANOVA/Kruskal-Wallis tests, and Kaplan-Meier methods. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) for overall (OS) and disease-specific survival (DSS), adjusting for age, sex, race, stage, grade, treatment, and metastasis status. RESULTS MTSCC patients were more often female (54.9%), Black (20.6%), and aged ≥70 years (50.5%) compared to ccRCC and PRCC (P < 0.001). MTSCC had a lower incidence of distant metastasis than ccRCC (8.7% vs. 9.5%), but higher than PRCC (4.2%). Although most MTSCC patients presented with early-stage disease and underwent surgery (87.9%), they had the shortest mean survival (47.9 months) and the highest proportion of deaths within 100 months (83.5%). Kaplan-Meier analysis showed higher early mortality for MTSCC, with survival curves converging after 75 to 100 months. In adjusted models, MTSCC was associated with a nonsignificant increase in mortality compared to ccRCC (OS HR: 1.36, P = 0.422; DSS HR: 1.13, P = 0.832), while PRCC had a significantly higher DSS risk (HR: 1.24, P = 0.001). Poor survival in MTSCC was associated with older age, high-grade tumors, distant metastases, and absence of surgery. CONCLUSION MTSCC shows distinct demographic and clinical features and a paradoxically shorter survival despite early-stage presentation. Early mortality may contribute to its poorer outcomes, indicating that MTSCC is not uniformly indolent. Closer surveillance and individualized risk assessment are warranted in selected patients.