Search Results (1,928)

Glaucoma is recognized as a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) is considered the only modifiable risk factor, current medical treatments are challenged by issues such as inadequate IOP control and ocular side effects. Rho kinase (ROCK) inhibitors have been developed as a novel pharmacologic class targeting the trabecular meshwork to enhance conventional aqueous humor outflow. In this review, the pharmacokinetics and IOP-lowering efficacy of key ROCK inhibitors are summarized. Beyond IOP reduction, ROCK inhibitors exhibit neuroprotective, anti-inflammatory, antifibrotic, and ocular perfusion-enhancing effects. Finally, we analyzed the limitations and future prospects of ROCK inhibitors in the management of glaucoma. Full article

Improving the green innovation quality (GIQ) of center cities is crucial to achieve sustainable urban agglomeration development. Utilizing data on green patent citations and economic indicators across cities in the Yangtze River Delta urban agglomeration (YRD) from 2003 to 2022, this research examines the influence of center cities’ GIQ on the economic performance of peripheral municipalities. The results show the following: (1) Center cities’ GIQ exerts a significant suppressive effect on peripheral cities’ economic growth overall. Heterogeneity analysis uncovers a distance-dependent duality. GIQ stimulates growth in proximate cities (within 300 km) but suppresses it beyond this threshold. This spatial siphoning effect is notably amplified in national-level center cities. (2) Mechanisms suggest that GIQ accelerates the outflow of skilled labor in peripheral cities through factor agglomeration and industry transfer mechanisms. Concurrently, it impedes the gradient diffusion of urban services, collectively hindering peripheral development. (3) Increased government green attention (GGA) and industry–university–research cooperation (IURC) in centers can mitigate these negative impacts. This paper contributes to the theoretical discourse on center cities’ spatial externalities within agglomerations and offers empirical support and policy insights for the exertion of spillover effects of high-quality green innovation from center cities and the sustainable development of urban agglomeration. Full article

Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological management of obstructive HCM (oHCM). This review offers an integrated and up-to-date synthesis of the cardiac myosin inhibitor class, with a focus on mavacamten, aficamten, and the broader landscape of emerging agents. It also highlights recent clinical trial outcomes, pharmacokinetic and pharmacogenetic considerations, and potential future directions in therapy. Furthermore, we incorporate the most recent data up to May 2025, including late-breaking trial results and real-world safety findings, aiming to provide clinicians with a practical and comprehensive perspective on this evolving drug class. A narrative review was conducted by systematically searching PubMed, Scopus, Google Scholar, and ClinicalTrials.gov for English-language articles and trials published between January 2016 and May 2025. Keywords included “cardiac myosin inhibitor”, mavacamten”, “aficamten”, “MYK-224”, and “hypertrophic cardiomyopathy.” Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. CMIs such as mavacamten and aficamten have demonstrated significant clinical benefits in reducing LVOT gradients, improving exercise capacity, and alleviating symptoms in patients with oHCM. Mavacamten is currently approved for clinical use, while aficamten is in advanced regulatory review. Comparative data suggest potential advantages of aficamten in the onset of action, pharmacokinetic profile, and tolerability. Emerging evidence supports the exploration of CMIs in pediatric populations, heart failure with preserved ejection fraction (HFpEF), and non-obstructive HCM (nHCM), although results are still preliminary. Cardiac myosin inhibitors offer a novel, pathophysiology-targeted approach to managing oHCM. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations. Full article

A systems-oriented review of machine learning (ML) over the entire flood management spectrum, encompassing fluvial flood control, pluvial flood management, and resiliency-risk characterization was undertaken. Deep learners like long short-term memory (LSTM) networks perform well in predicting reservoir inflows and outflows. Convolution neural networks (CNNs) and other object identification algorithms are being explored in assessing levee and flood wall failures. The use of ML methods in pump station operations is limited due to lack of public-domain datasets. Reinforcement learning (RL) has shown promise in controlling low-impact development (LID) systems for pluvial flood management. Resiliency is defined in terms of the vulnerability of a community to floods. Multi-criteria decision making (MCDM) and unsupervised ML methods are used to capture vulnerability. Supervised learning is used to model flooding hazards. Conventional approaches perform better than deep learners and ensemble methods for modeling flood hazards due to paucity of data and large inter-model predictive variability. Advances in satellite-based, drone-facilitated data collection and Internet of Things (IoT)-based low-cost sensors offer new research avenues to explore. Transfer learning at ungauged basins holds promise but is largely unexplored. Explainable artificial intelligence (XAI) is seeing increased use and helps the transition of ML models from black-box forecasters to knowledge-enhancing predictors. Full article

Urban heat island circulation (UHIC) determines the wind and thermal environments in urban areas. For Loess Tableland valley towns, the evolution characteristics of the UHIC over this negative terrain are not well understood, and therefore, it is important to investigate the evolution characteristics. A city-scale computational fluid dynamics (CSCFD) model is used, and simulation results are validated by the water tank experiment. The evolution process over such negative terrain can be divided into transient and quasi-steady stages, and in the transient stage, the airflow pattern evolves from thermal convection to city-scale closed circulation, while that in the quasi-steady stage is only city-scale closed circulation. In order to further reveal the characteristics of city-scale closed circulation, the sensitivities of different factors influencing the start time, outflow time, mixing height and heat island intensity are analyzed, and the most significant factors influencing these four parameters are urban heat flux, slope height, slope height, and potential temperature lapse rate, respectively. Finally, the dimensionless mixing height and heat island intensity for the valley town increase by 56.80% and 128.68%, respectively, compared to those for the flat city. This study provides guidance for the location and layout of built-up areas in the valley towns. Full article

The response of a temperature sensor in a gas stream depends on several heat transfer phenomena. The temperature of the thermocouple’s hot junction in the hot stream is lower than the measured temperature, which causes a measurement error. Compensation for this error and interpretation of the values indicated by the temperature sensor are possible by using a sensor dynamics model. Changes over time of the hot junction temperature as well as the entire thermocouple temperature in a stream are solved using the finite element method. Fluid flow and heat transfer equations are solved for a particular sensor geometry. This article presents a method for identifying a temperature sensor model using the results of numerical modeling of the response to temperature changes of the fluid stream, in which the input and output signal waveforms are recorded and then used by the estimator of a model coefficient. It is demonstrated that the dynamics of a bare-bead thermocouple sensor are well-described by a first-order transfer function. The proposed method was used to study the influence of stream velocity on the reaction of two sensors differing in the diameter of the wires, and the effect of radiative heat transfer on the model coefficients was examined by enabling and disabling selected models. The results obtained at several calculation points show the influence of the stream outflow velocity and selected geometric parameters on the value of the transfer function coefficients, i.e., transfer function gain and time constant. This study provides quantitative models of changes in sensor dynamics as functions of the coefficients. Full article

In this study, we examined the microclimates at eight entrances to a karst system distributed between an elevation of 812 and 906 m in Southern Spain. The karst system, characterised by subvertical open tectonic joints that form narrow shafts, developed on the slope of a mountainous area with a Mediterranean climate and strong chimney effect, resulting in an intense airflow throughout the year. The airflows modify the entrance temperatures, creating a distinctive pattern in each opening that changes with the seasons. The objective of this work is to characterise the outflows and find simple temperature-based parameters that provide information about the karst interior. The entrances were monitored for five years (2017–2022) with temperature–humidity dataloggers at different depths. Other data collected include discrete wind measurements and outside weather data. The most significant parameters identified were the characteristic temperature (T_y), recorded at the end of the outflow season, and the rate of cooling/warming, which ranges between 0.1 and 0.9 °C/month. These parameters allowed the entrances to be grouped based on the efficiency of heat exchange between the outside air and the cave walls, which depends on the rock-boundary geometry. This research demonstrates that simple temperature studies with data recorded at selected positions will allow us to understand geometric aspects of inaccessible karst systems. Dynamic high-airflow cave systems could become a natural source of evidence for climate change and its effects on the underground world. Full article

Given the significant shifts in rural labor mobility patterns and their continuous influence on the transformation of the land factor market, it is crucial to understand the relationship between labor factor prices and land factor prices. This understanding is essential to keep land factor prices within a reasonable range. This study establishes a theoretical framework to investigate how migrant workers’ return shapes land price formation mechanisms. Using 2023 micro-level survey data from eight counties in Jiangsu Province, China, this study empirically examines how migrant workers’ return affects land transfer prices and its underlying mechanisms through OLS regression and instrumental variable approaches. The findings show that under the current pattern of labor mobility, the outflow factor alone is no longer sufficient to exert substantial downward pressure on land transfer prices. Instead, the localized return of labor has emerged as a key driver behind the rise in land transfer prices. This upward mechanism is primarily realized through the following pathways. First, factor substitution effect: this effect lowers labor prices and increases the relative marginal output value of land factors. Second, supply–demand effect: migrant workers’ return simultaneously increases land demand and reduces supply, intensifying market shortages and driving up transfer prices. Lastly, the results demonstrate that enhancing the stability of land tenure security or increasing local non-agricultural employment opportunities can mitigate the effect of rising land transfer prices caused by the migrant workers’ return. According to the study’s findings, stabilizing land factor prices depends on full non-agricultural employment for migrant workers. This underscores the significance of policies that encourage employment for returning rural labor. Full article

Background: Iron deficiency (ID) is a prevalent comorbidity of heart failure (HF), affecting up to 59% of patients, regardless of the presence of anaemia. Although its negative impact on left ventricular (LV) function is well documented, its effect on right ventricular (RV) function remains unclear. This study assessed the effects of ID on RV global longitudinal strain (RV-GLS) in patients diagnosed with acute decompensated HF (ADHF). Methods: This study included data from 100 patients hospitalised with ADHF irrespective of LV ejection fraction (LVEF) value. ID was defined according to the European Society of Cardiology HF guidelines as serum ferritin <100 ng/mL or ferritin 100–299 ng/mL, with transferrin saturation <20%. Anaemia was defined according to World Health Organization criteria as haemoglobin level <12 g/dL in women and <13 g/dL in men. RV systolic function was assessed using parameters including RV ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC), peak systolic tissue Doppler velocity of the RV annulus (RV TDI S′), acceleration time of the RV outflow tract, and RV free wall GLS. Results: The mean (±SD) age of the study population (64% male) was 70 ± 10 years. The median LVEF was 35%, with 66% of patients classified with HF with reduced ejection fraction, 6% with HF with mid-range ejection fraction, and 28% with HF with preserved ejection fraction. Fifty-eight percent of patients had ID. There were no significant differences between patients with and without ID regarding demographics, LVEF, RV FAC, RV TDI S′, or systolic pulmonary artery pressure. However, TAPSE (15.6 versus [vs.] 17.2 mm; p = 0.05) and RV free wall GLS (−14.7% vs. −18.2%; p = 0.005) were significantly lower in patients with ID, indicating subclinical RV systolic dysfunction. Conclusions: ID was associated with subclinical impairment of RV systolic function in patients diagnosed with ADHF, as evidenced by reductions in TAPSE and RV-GLS, despite the preservation of conventional RV systolic function parameters. Further research validating these findings and exploring the underlying mechanisms is warranted. Full article

The envelopes of Red Supergiants (RSGs) have a unique chemical environment not seen in other types of stars. They foster an oxygen-rich synthesis but are tempered by sporadic and chaotic mass loss, which distorts the envelope and creates complex outflow sub-structures consisting of knots, clumps, and arcs. Near the stellar photosphere, molecules and grains form under approximate LTE conditions, as predicted by chemical models. However, the complicated outflows appear to have distinct chemistries generated by shocks and dust destruction. Various RSG envelopes have been probed for their molecular content, mostly by radio and millimeter observations; however, VY Canis Majoris (VY CMa) and NML Cygni (NML Cyg) display the highest chemical complexity, and also the most complicated envelope structure. Thus far, over 29 different molecules have been identified in the envelopes of RSGs. Some molecules are common for circumstellar gas, including CO, SiO, HCN and H₂O, which have abundances of ∼10⁻⁶–10⁻⁴, relative to H₂. More exotic oxides have additionally been discovered, such as AlO, AlOH, PO, TiO₂, and VO, with abundances of ∼10⁻⁹–10⁻⁷. RSG shells support intricate maser emission in OH, H₂O and SiO, as well. Studies of isotope ratios in molecules suggest dredge-up at least into the H-burning shell, but further exploration is needed. Full article

Accurate reservoir outflow simulation is crucial for water resource management. However, traditional machine learning-based simulation methods have not sufficiently considered the physical constraints of reservoir operation, which may lead to unrealistic issues such as negative outflows or water levels exceeding the reservoir’s own limitations. This study integrates physical constraints into the random forest (RF) model using the Sigmoid function, constructing a physics-constrained random forest model (PC-RF) for cascade reservoir outflow simulation. A stratified sampling strategy based on hydrological year types is used to create the training and validation datasets. The coefficient of determination (R²) and root mean square error (RMSE) are used to evaluate the model’s performance for medium- to long-term predictions of reservoir outflows on a 10-day time scale. Additionally, the mean decrease in impurity method is used to assess the importance of input features, thereby enhancing the model’s interpretability. The application the Yalong River cascade reservoir indicates that (1) compared to traditional RF, the PC-RF achieved significant breakthroughs, with an increase of 37.13% in the R² and a decrease of 60.04% in the RMSE when simulating outflows from the Lianghekou Reservoir, with all reservoirs maintaining an R² above 0.95, with no instances of unrealistic outcomes; (2) PC-RF effectively integrated historical operational patterns with top three features being previous period outflow, current inflow, and previous period inflow, providing interpretable insights for operational decision-making. The PC-RF model demonstrates high accuracy and practical potential in cascade reservoir outflow simulation, providing valuable applications for cascade reservoir management and water resource optimization. Full article

In Japan’s hilly and mountainous areas, which cover over 60% of the national land area, issues such as population outflow, aging, and regional decline are intensifying. This study explored sustainable decarbonization pathways by examining two representative regions (Maniwa City and Hidakagawa Town), while accounting for diverse regional characteristics. A bottom-up approach was adopted to calculate energy consumption and CO₂ emissions within residential and transportation sectors. Six future scenarios were developed to evaluate emission trends and countermeasure effectiveness in different regions. The key findings are as follows: (1) in the study areas, complex regional issues have resulted in relatively high current levels of CO₂ emissions in these sectors, and conditions may worsen without intervention; (2) if the current trends continue, per-capita CO₂ emissions in both regions are projected to decrease by only around 40% by 2050 compared to 2020 levels; (3) under enhanced countermeasure scenarios, CO₂ emissions could be reduced by >99%, indicating that regional decarbonization is achievable. This study provides reliable information for designing localized sustainability strategies in small-scale, under-researched areas, while highlighting the need for region-specific countermeasures. Furthermore, the findings contribute to the realization of multiple Sustainable Development Goals (SDGs), particularly goals 7, 11, and 13. Full article

Mitochondrial metabolism in the trabecular meshwork (TM) plays a critical role in maintaining intraocular pressure homeostasis by supporting the energy-demanding processes involved in aqueous humour outflow. In primary open-angle glaucoma, oxidative stress impairs mitochondrial function, leading to TM dysfunction. Therefore, understanding and targeting mitochondrial health in TM cells could offer a novel therapeutic strategy. Pyrroloquinoline quinone (PQQ) is a redox cofactor with antioxidant and mitochondrial-enhancing properties. However, its effects on human TM (HTM) cells remain largely unexplored. This study examined PQQ cytoprotective effects against H₂O₂-induced oxidative stress in HTM cells. Seahorse analyses revealed that PQQ alone improves mitochondrial respiration and ATP production. Moreover, PQQ mitigates H₂O₂-induced cellular damage and preserves mitochondrial function by normalising proton leak and increasing ATP levels. Furthermore, TEM and confocal microscopy showed that PQQ can partially alleviate structural damage, restoring mitochondrial network morphology, thereby leading to reduced cell death. Although these protective effects seem not to be mediated by changes in mitochondrial content or activation of the SIRT1/PGC1-α pathway, they may involve modulation of SIRT3, a key factor of mitochondrial metabolism and homeostasis. Overall, these results suggest that PQQ may represent a promising candidate for restoring mitochondrial function and reversing oxidative damage in HTM cells. Full article

Hydrogen is increasingly recognized as a key element of the transition to a low-carbon energy system, leading to a growing interest in accurate and sustainable assessment of its economic viability. Levelized Cost of Hydrogen (LCOH) is one of the most widely used metrics for comparing hydrogen production technologies and informing investment decisions. However, traditional LCOH calculation methods apply a single discount rate to all cash flows without distinguishing between the risks associated with outflows and inflows. This approach may yield a systematic overestimation of costs, especially in capital-intensive projects. In this study, we adapt a binary cash flow discounting model, previously proposed in the finance literature, for hydrogen energy systems. The model employs two distinct discount rates, one for costs and one for revenues, with a rate structure based on the required return and the risk-free rate, thereby ensuring that arbitrage conditions are not present. Our approach allows the range of possible LCOH values to be determined, eliminating the methodological errors inherent in traditional formulas. A numerical analysis is performed to assess the impact of a change in the general rate of return on the final LCOH value. The method is tested on five typical hydrogen production technologies with fixed productivity and cost parameters. The results show that the traditional approach consistently overestimates costs, whereas the binary model provides a more balanced and risk-adjusted representation of costs, particularly for projects with high capital expenditures. These findings may be useful for investors, policymakers, and researchers developing tools to support and evaluate hydrogen energy projects. Full article

This technical report presents a compelling case for the use of very-high-power, very-short-duration (VHPSD) radiofrequency ablation as a promising and efficient strategy for treating symptomatic premature ventricular contractions (PVCs) originating from the right ventricular outflow tract (RVOT). The patient with frequent, symptomatic PVCs and a 24% burden underwent successful ablation using a 90 W/4 s recipe via the QDOT MICRO™ catheter. The procedure resulted in immediate and sustained elimination of PVCs, with only 4 s of ablation time, near-zero fluoroscopy, no complications, and no PVC recurrence at 6 months. VHPSD ablation, though originally developed for atrial fibrillation, demonstrated remarkable procedural efficiency, precision, and lesion efficacy in this case. Compared to standard power, long-duration (SPLD) ablation, VHPSD offers the potential to significantly reduce procedural time, minimize tissue edema, and lower complication risk, particularly advantageous in anatomically challenging areas or in situations where maintaining stable catheter contact for extended periods is difficult or unfeasible. This technical report suggests the transformative potential of VHPSD as a first-line ablation strategy for RVOT-PVCs, provided careful mapping and appropriate technique are used. It underscores the need for further prospective studies to validate its broader safety, efficacy, and role in PVC management, particularly in cases involving intramural origins. Full article