Search Results (432)

Osteoarthritis involves complex interactions between articular joint tissues and the immune system, which is implicated in molecular trafficking via barrier-function modulating cytokines. The current study aims to test effects of an acute spike in TNF-α or TGF-β on vascular barrier function at multiple length scales, from the heart to tissue compartments of the knee, and cellular inhabitants of those respective compartments, in a spontaneous guinea pig model of osteoarthritis. First we quantified the intensity of a fluorescent-tagged 70 kDa tracer, similar in size to albumin, the most prevalent transporter protein in the blood, in tissue compartments of bone (periosteum, marrow space, compact bone, and epiphyseal bone) and cartilage (superficial cartilage, calcified cartilage, and the interface between, i.e., the epiphyseal line), as well as at sites of tendon attachment to bone (entheses). We then examined tracer presence and intensity in the respective pericellular and extracellular matrix zones of bone and cartilage. Acute exposure to TGF-β reduced barrier function (increased permeability) at nearest vascular interfaces in four of eight tissue compartments studied, compared to TNF-α where one of eight tissue compartments showed significant diminishment in barrier function. The increase in permeability associated with reduced barrier function was observed at both tissue compartment and cellular length scales. The observation of pericellular transport of the albumin-sized molecules to osteocytes contrasts with previous observations of barrier function in healthy, untreated animals and is indicative of increased molecular transport in pericellular regions of musculoskeletal tissues in cytokine-treated animals. Understanding age- and disease-related changes in molecular transport within musculoskeletal structures, such as the knee joint, is crucial for elucidating the etiology and pathogenesis of osteoarthritis. Full article

The investigation of complex karst systems has always been a difficult task for hydrogeologists, especially related to the spatial position of karst channels. The city of Pirot, which is located in southeastern Serbia, taps karst water for water supply from three karstic springs (Kavak, Krupac and Gradište), which are characterized by extremely good and stable groundwater regime and quality. According to the general water regime, it can be concluded that in addition to the development of shallow and large karst conduits (as proven by tracer tests), there are also deeper karst channels, in which water circulates very slowly and remains for much longer. In order to understand the genesis and characteristics of karst springs used for water supply, multi-parameter research was conducted, which, in addition to monitoring the yield on a daily basis, also included detailed hydrochemical research together with an analysis of microelements and stable and radioactive isotopes. Water from springs has a stable hydrochemical composition highlighting prolonged contact with the host rock. Isotopic analysis showed that the water is a mixture of young waters (residing in the system for a few days, as determined by tracer tests); semi-young waters that, based on the radioactive isotopes ³T and ³He, have resided in the system for 53 years; and very old waters that have spent more than 3000 years in the system. Finally, such new data on significant dynamic as well as static reserves of quality drinking water are of particular importance for long-term sustainable water utilization. Full article

Objective: Accurate diagnosis of sentinel lymph node (SLN) status after neoadjuvant therapy (NAT) for breast cancer is crucial for guiding axillary management. This study aimed to evaluate novel contrast-enhanced ultrasound (CEUS) patterns for assessing SLNs following NAT. Methods: We retrospectively analyzed clinical and imaging data from 279 breast cancer patients who completed NAT and underwent surgery between June 2019 and December 2024. Preoperative SLN evaluations included percutaneous CEUS (PCEUS), intravenous CEUS (IVCEUS), and conventional ultrasound (CUS). Intraoperative SLN biopsy was performed using methylene blue tracer, with pathological results serving as the gold standard. Diagnostic efficacy was compared among CUS, previously used PCEUS patterns, newly proposed PCEUS, IVCEUS, and combined CEUS. Results: The newly proposed PCEUS classified SLNs into six types, while IVCEUS categorized enhancement into three sequences and four patterns. Among the 347 SLNs detected via PCEUS, 292 (84.15%) were benign and 55 (15.85%) were malignant. The newly proposed PCEUS demonstrated higher diagnostic efficacy compared to CUS, prior PCEUS patterns, IVCEUS, and combined CEUS, with sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve of 49.1% (27/55), 86.3% (252/292), 40.3% (27/67), 90.0% (252/280), 80.4% (279/347), and 0.677 (95% CI: 0.625–0.726), respectively. However, DeLong tests revealed no statistically significant differences between the methods (all p > 0.05). Conclusions: The novel CEUS classification improved diagnostic accuracy for SLNs after NAT, though accuracy remains relatively low. Future integration of artificial intelligence may further enhance diagnostic efficacy. Full article

This article presents an experimental study on the hydrodynamics of coolant flow within the pressure vessel of a small modular reactor (SMR) cooled with water, including areas such as the annular downcomer, bottom chamber, and core-simulating channels that are being developed for use in land-based nuclear power plants. This paper describes the experimental setup and test model, measurement techniques used, experimental conditions under which this research was conducted, and results obtained. This study was conducted at the Nizhny Novgorod State Technical University (NNSTU) using a high-pressure aerodynamic testing facility and a scale model that included structural components similar to those found in loop-type reactors. Experiments were performed with Reynolds numbers (Re) ranging from 20,000 to 50,000 in the annular downcomer space of the test model. Two independent techniques were used to simulate the non-uniform flow field in the pressure vessel: passive impurity injection (adding propane to the airflow) and hot tracer (heating one of the reactor circulation loops). The axial velocity field at the inlet to the reactor core was also investigated. This study provided information about the spatial distribution of a tracer within the coolant flow in the annular downcomer and bottom chamber of the pressure vessel. Data on the distribution of the contrasting admixture are presented in plots. The swirling nature of the coolant flow within the pressurized vessel was analyzed. It was shown that the intensity of mixing within the bottom chamber of the pressure vessel is influenced by the presence of a central vortex. Parameters associated with the mixing of admixtures within the model for the pressure vessel were estimated. Additionally, the possibility for simulating flow with different temperature mixing processes using isothermal models was observed. Full article

Backward Lagrangian stochastic modeling is widely used to estimate emission rates from land surfaces to the atmosphere. It is also applied to calculate concentrations of pollutants due to known emission sources. A key component of this modeling technique is the concentration estimator, which relies on tracer particle trajectories to establish the relationship between concentration, emission rate, and meteorological condition. A commonly used concentration estimator is closely examined and shown to have potential inaccuracies. An alternative estimator is derived and compared with the existing one. The new estimator is tested using backward Lagrangian stochastic modeling in both Gaussian and non-Gaussian turbulence. The results demonstrate that, in many cases, the two estimators are equivalent, which explains the general success of the popular estimator. However, if the vertical velocities of some tracer particles are extremely slow when hitting the source, a significantly higher ratio of concentration to emission rate will be obtained. This spuriously high ratio will result in overestimation of the concentration if the purpose is to calculate concentrations from a known emission rate and underestimation of the emission rate if the model is used to calculate the emission rate from measured concentrations. The new estimator can avoid this unjustifiable behavior and therefore exhibits superior performance. Full article

Background/Objectives: Cardiac sarcoidosis (CS) is a granulomatous inflammatory cardiomyopathy with heterogeneous presentations, from palpitations to heart failure and sudden cardiac arrest. Despite advances in imaging and immunosuppressive (IS) therapy, relapse patterns and long-term outcomes remain poorly defined. This study aimed to characterize relapse and identify predictors of relapse and major adverse cardiac events (MACE) in a real-world CS cohort. Methods: This retrospective single-center study included 25 adults diagnosed with CS at Geneva University Hospitals between 2016 and 2024, classified per the 2024 American Heart Association diagnostic criteria. Relapse was defined as clinical, arrhythmic, or imaging deterioration requiring treatment escalation. MACE included cardiovascular hospitalization, device therapy, left ventricular assist device, heart transplant, or death. Statistical methods included Kaplan–Meier analysis with log-rank tests and multivariable Cox regression adjusted for age and sex. Results: Relapse occurred in 13 patients (56%), frequently subclinical (61.5%) and detected incidentally on routine PET-CT during IS tapering. In the multivariate model, predictors of relapse included right ventricular FDG uptake (aHR 13.1; 95% CI 1.3–133.7; p = 0.03) and second-line immunosuppression duration ≤24 months (aHR 20.1; 95% CI 1.1–363.8; p = 0.04). Relapse-free patients were more often maintained on dual or triple IS therapy (71.4% vs. 15.4%; p = 0.02) and low-dose prednisone (<10 mg/day) (57.1% vs. 7.7%; p = 0.03). Conclusions: Relapse is common in CS, often subclinical, and associated with PET-CT findings and premature IS tapering. Maintenance therapy may reduce risk. Multimodal imaging remains critical for disease monitoring, though tracers with higher specificity are needed. Further research should refine relapse definitions and support personalized treatment strategies. Full article

Preferential flow in coal mining subsidence areas leads to shallow soil moisture loss, vegetation reducing and ecological degradation. However, the factors influencing the development of preferential flow remain unclear. This study analyzed the morphological characteristics of preferential flow using a staining tracer test in coal mining subsidence areas along the middle reaches of the Yellow River Basin. Characteristic parameters including the dye-stained area ratio, preferential flow ratio, length index, variation coefficient were comparatively evaluated under different initial soil moisture conditions. Results showed that shallow soils exhibited substrate flow, while preferential flow occurred in deeper soil layers below the matrix flow. As initial soil moisture increased, the extent of both substrate flow and preferential flow decreased. The dye-stained area ratio declined with increasing soil depth, and the relationship between dye-stained area and soil layer depth was best described by a cubic function. Higher initial soil moisture reduced maximum infiltration depth and length indices while increasing the coefficient of the stained pattern. Furthermore, a higher of initial soil water content corresponded to a lower preferential flow index. Overall, increased initial soil moisture may reduce the extent of preferential flow and the rapid infiltration of water into soil. These findings provides a basis for further hydrological studies in coal mining subsidence areas in arid and semi-arid regions and offer scientific support for ecological restoration efforts in mining areas. Full article

Objectives: We sought to document interim methodologic improvements and preliminary results for pulmonary suffusion. Methods: A Phase I/II trial of thoracoscopic lung suffusion for resectable sarcoma and colorectal carcinoma metastases followed a pilot study on oligometastatic lung malignancy at a comprehensive cancer center. Primary-specific chemotherapy doses (cisplatin, oxaliplatin, doxorubicin, or gemcitabine) suffused unilaterally for 30 min were escalated to amplify regional deliveries three-fold. Drug delivery was measured with tissue, blood samples, and ⁹⁹Tc; pulmonary function tests and clinical adverse events (AEs) assessed safety and tolerance. Results: From 2008–2025, 31 ECOG 0–2 patients (10 male) aged 33–75 years had unilateral lung suffusion (16 right, 14 left, 1 aborted, and 8 sides selected randomly). Vascular occlusion intolerance was immediate or delayed (25 min) in two cases. Two catheter-positioning grade 3 AEs occurred: hypotension with troponin leak (1) and atrial fibrillation (1). Patients averaged 1.3 ± 1.2 metastasectomies (17 sub-lobar, 8 lobar resections, and 2 intentional open cytoreductive metastasectomies). Hospitalizations were brief (1–4 days) except for 6–7 day stays in the only two open cases and one doxorubicin (grade 4 hypoxic respiratory failure) case. Ninety-day survival was 100%, and the Phase I delivery goal of 12.75 mg/m² 65 (15% systemic) was achieved for oxaliplatin. Lung function was preserved according to ⁹⁹Tc differentials within 6.1 ± 7.1% of the predicted reductions at 30 days. Sampling delays, tracer discordances, and atypical pharmacokinetics reduced tissue drug detections. Recent pulmonary artery snaring cases (two) demonstrated in-flow control more stable than that of balloon occlusions. Conclusions: Suffusion for metastatic malignancies appears safe and warrants further investigation. Full article

This study was conducted to reveal the response relationship between soil preferential flow characteristics and soil pore structure of sloping cropland under contour antislope step measures in the alpine canyon area of Southwest China. In the sub-watershed of Nantangjing, Yunlong County, the upper and lower slopes of primary sloping cultivated land (PSC) and contour reverse-slope terraced rectified land (CR) were used for the study, and a field staining tracer test was used to compare the differences in preferential flow morphology between different slopes with and without measures. The maximum infiltration depth of preferential flow under the contour reverse-slope terrace land preparation reached 21 cm. The stained area ratio tended to decrease with increasing soil depth. Compared to the original slope farmland, the stable infiltration rate under land preparation increased from 0.017 to 0.244 cm³·s⁻¹, and the maximum macroporosity increased by up to 17.00%. Furthermore, land preparation measures significantly enhanced the correlation between macropore quantity and preferential flow characteristics, with the highest correlation coefficient reaching 0.98. And the soil factors in total porosity, total nitrogen and organic matter were particularly influential on preferential flow. Contour antislope terracing promotes the formation and development of preferential soil flow by remodeling soil structure and optimizing pore network distribution. Full article

Understanding solute transport across interfaces between different porous materials is crucial for subsurface applications. Column tracer experiments have suggested solute accumulation at these interfaces. This effect cannot be explained by standard models based on Fickian flux continuity and the advection–dispersion equation. To analyze this phenomenon, we present reactive transport experiments in a 2D intermediate-scale horizontal tank to visualize and evaluate the spatiotemporal evolution of a solute plume crossing a sharp interface between coarse and fine materials. The plume results from the reaction of two fluid solutions entering the tank in parallel through inlet ports. The reaction product is analyzed using mixing and reaction metrics. Results show the reaction product encounters anomalous resistance when the plume crosses the coarse-to-fine (CF) interface. This effect is less pronounced in the fine-to-coarse (FC) transition. This asymmetric resistance does not produce solute accumulation behind the interface, a difference from the results obtained with the one-dimensional model. Instead, results show enhanced transverse spread of the reaction product in the coarse-to-fine transition, with slow release in the fine material. A sudden decrease in the longitudinal concentration profile across the interface is observed. Mixing metrics show that as apparent transverse dispersivity increases closer to the interface in the CF transition, the scalar dissipation rate and total mass reacted increase, indicating that the CF configuration promotes greater solute reactivity near the interface compared to the FC configuration. Full article

Background/Objectives: ¹⁸F-PSMA-1007 is one of the more widely used radioligands in prostate cancer imaging with PET/CT. Its major advantage lies in the low urinary tracer activity due to primarily hepatobiliary clearance, but unexpectedly high tracer accumulation in the bladder can occur, potentially hindering assessment of lesions near the prostate bed. This study assesses the impact of furosemide on ¹⁸F-PSMA-1007 tracer accumulation in the bladder. Methods: In this single-center, retrospective, intra-individual comparative analysis, 18 patients undergoing two consecutive ¹⁸F-PSMA-1007 PET/CT scans for biochemical relapse (BCR) or persistence (BCP)—one with and one without prior furosemide administration—were included. Images were acquired 60 min post-injection of 250 MBq of tracer activity. Standardized Uptake Values (SUVmax, SUVpeak, SUVmean) were measured in the bladder and in tissues with physiological uptake by three readers. Differences were analyzed using Wilcoxon signed-rank tests. The inter-reader agreement was assessed using intraclass correlation coefficient. Results: Furosemide significantly decreased bladder SUVmax, SUVpeak, and SUVmean (all p < 0.001). Mean bladder SUVmax decreased from 13.20 ± 10.40 to 3.92 ± 3.47, SUVpeak from 10.94 ± 8.02 to 3.47 ± 3.13, and SUVmean from 8.74 ± 6.66 to 2.81 ± 2.56, representing a large effect size (r ≈ 0.55). Physiological tracer uptake in most organs was not significantly influenced by furosemide (all p > 0.05). Conclusions: Despite the predominantly hepatobiliary clearance of ¹⁸F-PSMA-1007, furosemide-induced forced diuresis leads to a significant reduction in tracer activity in the bladder, which in clinical practice could help in early detection of tumor recurrence. Full article

Accurate methane emission estimates are essential for climate policy, yet current field methods often struggle with spatial constraints and source complexity. Ground-based mobile approaches frequently miss key plume features, introducing bias and uncertainty in emission rate estimates. This study addresses these limitations by using small unmanned aerial systems equipped with precision gas sensors to measure methane alongside co-released tracers. We tested whether arc-shaped flight paths and alternative ratio estimation methods could improve the accuracy of tracer-based emission quantification under real-world constraints. Controlled releases using ethane and nitrous oxide tracers showed that (1) arc flights provided stronger plume capture and higher correlation between methane and tracer concentrations than traditional flight paths; (2) the cumulative sum method yielded the lowest relative error (as low as 3.3%) under ideal mixing conditions; and (3) the arc flight pattern yielded the lowest relative error and uncertainty across all experimental configurations, demonstrating its robustness for quantifying methane emissions from downwind plume measurements. These findings demonstrate a practical and scalable approach to reducing uncertainty in methane quantification. The method is well-suited for challenging environments and lays the groundwork for future applications at the facility scale. Full article

The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article

The design of emulsions at the nanoscale is a significant application of nanotechnology. For spherical droplets and a given volume of dispersed phase, the nanometre size of droplets inversely increases the total area, $A={\displaystyle \frac{3V}{r}}$, allowing greater contact with organic and inorganic materials during application. In topical applications, not only is cell contact increased, but also permeability in the cell membrane. Nanoemulsions typically achieve kinetic stability rather than thermodynamic stability, so their commercial application requires reasonable resistance to flocculation and coalescence, which can be affected by temperature changes. Therefore, their thermoresponsive characterisation becomes relevant. In this work, we analyse this response in an O/W nanoemulsion of Palmarosa for antibacterial purposes that has already shown stability for one year at controlled room temperature. We now study hysteresis processes and the behaviour of the statistical distribution in droplet size by Dynamic Light Scattering, obtaining remarkable stability under temperature changes up to 50 °C. This includes a maintained chemical composition observed using Fourier Transform Infrared Spectroscopy and the preservation of antibacterial properties analysed through optical density tests on cultures and the Spread-Plate technique for bacteria colony counting. We obtain practically closed hysteresis curves for some tracers of droplet size distributions through controlled thermal cycles between 10 °C and 50 °C, exhibiting a non-linear behaviour in their distribution. In general, the results show notable physical, chemical, and antibacterial stability, suitable for commercial applications. Full article

Assessment of contaminant dispersal in sandstones requires hydraulic characterization with a combination of datasets that span from the core plugs to wellbores and up to the field scale as the matrix and fractures are both hydraulically conductive. Characterizing the hydraulic properties of the matrix is fundamental because contaminants diffuse into the fractured porous blocks. Fractures are highly conductive, and the determination of the number of hydraulically active rock discontinuities makes discrete fracture network models of solute transport reliable. Recent advances (e.g., active line source temperature logs) in hydro-geophysics have allowed the detection of 40% of hydraulically active fractures in a lithified sandstone. Tracer testing has revealed high (~10⁻⁴–10⁻² ms⁻¹) flow velocities and low (~10⁻²–10⁻⁴) effective porosities. Contaminants can therefore move rapidly in the subsurface. The petrophysical characterization of the plugs extracted from the cores, in combination with borehole hydro-geophysics, allows the characterization of either matrix or fracture porosity, but the volume of sandstone characterized is low. Tracer tests cannot quantify matrix or fracture porosity, but the observation scale is larger and covers the minimum representative volume. Hence, the combination of petrophysics, borehole hydro-geophysics, and tracer testing is encouraged for the sustainable management of solute transport in dual porosity sandstones. Full article