Search Results (246)

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become highly prevalent worldwide, and its pathogenesis and progression mechanisms remain incompletely understood. An increased activation of innate immune cells in the liver contributes to hepatic fibrogenesis via a chronic loop of inflammation and regeneration processes. Among them are mast cells (MCs), whose role in hepatic cirrhosis secondary to MASLD remains poorly studied. Our aim was to evaluate differences in MC density in cirrhotic liver tissue among patients with MASLD and other chronic liver disease etiologies. For this, a retrospective study of MC count was performed in cirrhotic liver explants obtained from MASLD, alcohol-related liver disease (ALD), and autoimmune hepatitis (AIH). We included a control group of subjects without liver damage. Tryptase-positive MCs were identified by indirect immunofluorescence and quantified as MC density per low-power field (MC/LPF). Group differences were analyzed using the Kruskal–Wallis test with Dunn’s multiple comparisons, considering p < 0.05 as statistically significant. A significantly higher MC density was observed in MASLD, ALD, and AIH patients compared with the control group. The group analysis showed that ALD patients exhibited higher MC density than AIH, with no observed difference between ALD and MASLD. MC density was correlated positively with tobacco smoking and alcohol use in the full analyzed group, suggesting them as risk factors of high MC liver infiltration. We conclude that MC density is augmented in MASLD-related cirrhosis, highlighting potential links between lifestyle factors and MC-mediated hepatic inflammation. Future studies should explore the mechanisms driving this association and evaluate whether targeting MCs could help mitigate fibrosis progression. Full article

Background/Objectives: For many patients with malignant spinal cord compression (MSCC) not suitable for surgery, irradiation alone is the preferred treatment. A dose-fractionation regimen of 10 × 3 Gy is common for this situation. Since most patients suffer from motor deficits and pain, the number of radiotherapy sessions should be as low as possible. A secondary analysis of a phase 2 trial compared 5 × 5 Gy to a historical control group treated with 10 × 3 Gy. After 1:2 matching, 5  ×  5 Gy appeared similarly effective regarding local progression-free survival (LPFS) at 6 months, motor function, walking ability, and overall survival. Methods: This retrospective study investigated whether these findings are consistent in a larger cohort and after longer follow-up. Additional data were gathered for the phase 2 cohort, follow-up in the control group was not limited to 6 months, and the number of patients in the control group increased from 213 to 728. Results: After propensity-score matching, no significant differences were found regarding LPFS after 12 (p = 0.198), 18 (p = 0.139), and 24 (p = 0.117) months, effect on motor function (p = 0.393), walking ability (p = 0.079), 24-month local control (p = 0.655), and 24-month OS (p = 0.403). Conclusions: Given the limitations of this study, 5 × 5 Gy appears preferable to 10 × 3 Gy in selected patients receiving irradiation without upfront surgery. Clinicians should balance initial convenience for the patients and future limitations when re-irradiation in the same part of the spine is required. Full article

Responses to palliative radiotherapy (RT) for metastatic lesions vary among patients, and molecular determinants of radiosensitivity remain unclear. This study investigated genomic features associated with local progression-free survival (LPFS) in metastatic breast cancer patients treated with palliative RT. Forty-four patients who underwent next-generation sequencing of 523 cancer-related genes were retrospectively analyzed. The biologically effective dose (BED) was calculated using an α/β ratio of 3 Gy, and local progression was defined as recurrence or progression within the irradiated field. A total of 60 metastatic lesions, predominantly in bone (68.3%), were evaluated. Higher BED (≥88 Gy) was significantly associated with longer LPFS (p = 0.011). Among 320 detected mutations mapped to 141 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the PI3K–Akt signaling pathway remained an independent predictor in multivariate analysis (p = 0.03). Subgroup analyses demonstrated that patients with Ras, PI3K–Akt, or FoxO pathway mutations derived greater LPFS benefit from high BED, whereas this advantage was confined to wild-type tumors for the PD-L1/PD-1 checkpoint and choline metabolism pathways. These findings suggest that pathway-specific molecular contexts modulate RT response and may inform individualized radiation dose strategies in metastatic breast cancer. Full article

Low noise and low power neural recording amplifiers are required for implantable devices measuring action potentials. This paper presents a dynamic current pulsing technique combined with a special type of two-stage low-pass filter (LPF) that demonstrates an improvement in the noise efficiency factor (NEF) beyond that achievable using traditional design. A low NEF of 1.55 is achieved at an average power consumption of 587.8 nW and 5.18 µVrms noise, integrated from 0.1 to 9.8 kHz, inclusive of the impacts of sampling and aliasing. The NEF is improved from 1.76 in the static low current state (LCS) and 1.67 in the static high current state (HCS), measured on the same amplifier chip. Full article

Background/Objectives: Despite increasing use of upfront decompressive surgery for malignant epidural compression of the myelon (MESCC), a substantial number of affected patients still receive radiotherapy (RT) alone. Many of these patients would benefit from a personalized treatment approach including the most appropriate dose-fractionation regimen. The PRE-MODE trial (NCT03070431) compared precision RT with 5 × 5 Gy (prospective cohort, n = 40) to conventional RT with 5 × 4 Gy (historical control, n = 676)). After propensity-score matching, 5 × 5 Gy resulted in significantly increased local progression-free survival (LPFS) at 6 months than 5 × 4 Gy. The question arose whether this benefit is still present after a longer period of follow-up. Methods: For this additional study, supplementary data were retrospectively captured, resulting in prolongation of follow-up until 24 months. Results: 5 × 5 Gy resulted in LPFS of 80.9% at each investigated time point (12, 18, and 24 months) without reported radiation myelopathy. Moreover, 5 × 5 Gy showed a trend towards improved LPFS after 12 (p = 0.070), 18 (p = 0.060), and 24 (p = 0.054) months. Similarly to the original PRE-MODE trial, OS-rates were not significantly different in the dose groups of this supplementary study. Conclusion: Since 5 × 5 Gy resulted in excellent long-term LPFS and showed a trend towards better outcomes up to 24 months following RT, it appears preferable to 5 × 4 Gy and will contribute to the personalized treatment of patients with MESCC who are assigned to RT alone without upfront neurosurgical intervention. Full article

This paper presents the implementation of the Grid-Forming (GFM) control technique in renewable energy source inverters to synchronize with the grid and provide frequency support. Specifically, the GFM Droop Control technique, based on the Power–Frequency relationship, is employed. The proposed model was developed and validated in the Matlab-Simulink environment. By using electromagnetic transient (EMT) simulations, we were able to precisely monitor and analyze voltage and current waveforms, thereby confirming the approach’s effectiveness in enhancing grid stability and power quality. The implementation of the GFM control technique in islanded mode demonstrated high system frequency stability. In response to sudden load changes up to 5 MW (equivalent to over 30% of the total load), a maximum frequency deviation of 0.04 Hz and a maximum Rate of Change of Frequency (RoCoF) of 4 Hz/s were observed. The system ensured the frequency’s return to its nominal value of 60 Hz, thanks to the virtual inertia and frequency regulation provided by the GFM. The total harmonic distortion (THD) of current and voltage in steady-state operation consistently remained below 1%, thus complying with IEEE 1547 standards. In tests with the GFM interconnected to the grid, the droop+LPF control provided dynamic support to the external system, effectively mitigating both frequency deviations and RoCoF. The GFM contributes to the grid’s frequency stability by providing virtual inertia. The power quality at the point of common coupling (PCC) was excellent, as the voltage distortion was maintained below 0.5%, confirming that the injection of harmonic currents does not violate established limits. Full article

Objectives: This study aimed to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for spinal metastases, focusing on pain control, local tumor control, and the incidence of vertebral compression fractures (VCF). Materials and Methods: We retrospectively analyzed 179 patients with 217 spinal metastatic lesions who underwent SBRT between July 2020 and April 2022. The prescribed doses for SBRT were 18 or 20 Gy for one fraction, ≥24 Gy for three fractions, ≥20 Gy for four fractions, and ≥25 Gy for five fractions. Patient-reported treatment response was evaluated 1–3 months after SBRT completion. Local recurrence was defined as failure within the radiotherapy field. Pain response, local progression-free survival (LPFS), and the incidence of painful VCF were assessed. Prognostic factors for LPFS and VCF risk factors were evaluated. Results: The overall pain response rate was 80.8%. LPFS rates were 90.6% at 1 year and 83.0% at 2 years. Lytic/mixed lesions and involvement of multiple segments were significant prognostic factors for reduced LPFS. The cumulative incidence of painful VCF was 8.7% at 1 year and 12.8% at 2 years. A biologically effective dose (BED₃) ≥104 Gy was the only significant risk factor for painful VCF. Conclusions: SBRT demonstrated high efficacy for pain and local tumor control in spinal metastases, with an acceptable VCF risk. Full article

This paper presents a novel self-packaged low-pass filter (LPF) based on the substrate-integrated suspended line (SISL) technique, employing a high-impedance line structure. The core circuit of the proposed LPF integrates three distinct transmission line technologies: stripline (SL), grounded coplanar waveguide (GCPW), and SISL. Leveraging these advanced techniques, the prototype LPF with a cutoff frequency (f₀) of 3 GHz has been successfully designed and fabricated. Comprehensive measurements reveal that the LPF exhibits an insertion loss (S₂₁) of greater than −0.74 dB within the pass-band, while maintaining a stop-band ranging from 5 GHz to 12.2 GHz, achieving a suppression level exceeding 15 dB. Additionally, the highest internal solid-line impedance reaches 110 Ω. Given its superior performance characteristics, the proposed LPF is highly suitable for application in radio frequency (RF) front-end systems, specifically for filtering and screening signals within designated frequency bands. Full article

Background/Objectives: In Spain, pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related death, with only 20% of patients eligible for surgery at diagnosis. For the remaining majority, prognosis is poor and effective non-surgical strategies are needed. Stereotactic MR-guided adaptive radiotherapy (SMART) may facilitate the delivery of ablative doses of radiation safely with low toxicity. This study reports the first national experience in Spain with SMART for patients with borderline resectable (BRPC) or locally advanced pancreatic cancer and evaluates its feasibility, safety, and early clinical outcomes. Methods: A prospective observational study was conducted including 28 patients with histologically confirmed BRPC or LAPC treated between August 2023 and December 2024. All patients received induction chemotherapy—mainly FOLFIRINOX (57.1%)—followed by SMART delivered in five fractions (40–50 Gy) using a 0.35T MR-guided linear accelerator. Daily online adaptive recontouring and replanning were performed for all 140 treatment fractions. Toxicities were assessed using CTCAE v5.0, and survival outcomes were estimated using Kaplan–Meier analysis. Results: The median patient age was 67 years, and 71.4% of tumors were located in the pancreatic head. At a median follow-up of 7.4 months after SMART (12.25 months from diagnosis), 6-month local progression-free survival (LPFS) was 89.3% from the start of SMART and 82.1% from diagnosis. Distant progression-free survival (DPFS) at 6 and 12 months was 92.9% and 68.2%, respectively. Median progression-free survival (PFS) was 11.5 months, and the median treatment-free interval was 5.7 months. Median overall survival (OS) was not reached; 6- and 12-month OS rates were 89.3% and 74.1%, respectively. Treatment-related toxicity was limited to grade 2 abdominal pain in 14.3% of patients, with no grade ≥3 adverse events attributed to SMART. Conclusions: SMART is a feasible and safe treatment modality for BRPC and LAPC in real-world clinical practice. These encouraging early outcomes support further clinical investigation and broader implementation. Full article

The sustainable intensification of forage production in Mediterranean climates requires technological solutions that optimize the use of agricultural inputs. This study aimed to evaluate the performance of proximal optical sensors in recommending and monitoring variable rate nitrogen fertilization in winter forage crops cultivated under Mediterranean conditions. A handheld multispectral active sensor (HMA), a multispectral camera on an unmanned aircraft vehicle (UAV), and one passive on-the-go sensor (OTG) were used to generate real-time nitrogen (N) application prescriptions. The sensors were assessed for their correlation with agronomic parameters such as plant fresh matter (PFM), plant dry matter (PDM), plant N content (PNC), crude protein (CP) in%, crude protein yield (CPyield) per unit of area, and N uptake (NUp). The real-time N fertilization stood out by promoting a 15.23% reduction in the total N fertilizer applied compared to a usual farmer-fixed dose of 150 kg ha⁻¹, saving 22.90 kg ha⁻¹ without compromising crop productivity. Additionally, NDVI_OTG showed moderate simple linear correlation with PFM (R² = 0.52), confirming its effectiveness in prescription based on vegetative vigor. UAV_II (NDVI after fertilization) showed even stronger correlations with CP (R² = 0.58), CPyield (R² = 0.53), and NUp (R² = 0.53), highlighting its sensitivity to physiological responses induced by N fertilization. Although the HMA sensor operates via point readings, it also proved effective, with significant correlations to NUp (R² = 0.55) and CPyield (R² = 0.53). It is concluded that integrating sensors enables both precise input prescription and efficient monitoring of plant physiological responses, fostering cost-effectiveness, sustainability, and improved agronomic efficiency. Full article

The recently developed localized particle filter (LPF) is extended to a fully coupled general circulation model (CGCM), specifically the Community Earth System Model (CESM), to assess its efficacy in assimilating multisource ocean observations, including satellite sea surface temperature (SST) and in situ temperature and salinity (TS) profiles. The LPF introduces localization in the weighting and resampling steps to avoid the filter degeneracy problem, thereby enhancing its performance in assimilating nonlinear systems. Data assimilation experiments using real ocean observations reveal that the LPF has notable advantages in improving the quality of subsurface and deep ocean temperature and salinity, particularly below 200 m. The results are evaluated against objective analysis data, confirming the potential applicability of the LPF in operational settings. Furthermore, a comparative analysis with the ensemble adjustment Kalman filter (EAKF) elucidates the merits and limitations of the LPF, and further underscores the pronounced advantage of LPF in the deep ocean. However, when TS profiles are already assimilated, supplementing the LPF with additional SST data produces adverse effects, a behavior markedly different from that of the EAKF. This discrepancy signals the need for refined data pre-processing strategies within the LPF in real operational applications. Full article

Background and Objectives: Specialized nurses play an essential role in managing pulmonary fibrosis. While tele-nursing has the potential to optimize disease management, current evidence regarding its impact remains limited. This study aimed to evaluate a tele-nursing intervention that provided unscheduled access to a specialized nurse via phone or email for both patients and caregivers. Materials and Methods: This was a prospective, single-center, open-label, and pre–post pilot study. Participants and their caregivers were provided with direct access to a specialized nurse, by phone and email, for unscheduled consultations. Patient-reported experience measures (PREMs) and patient-reported outcome measures (PROMs) were collected at baseline and after three months of tele-nursing access. PREMs were assessed using a 10-point Likert scale questionnaire, and PROMs were evaluated using the King’s Brief Interstitial Lung Disease (K-BILD) and the Living with Pulmonary Fibrosis (L-PF) questionnaires. Results: A total of 47 patients with pulmonary fibrosis receiving antifibrotic drugs were enrolled. At three months, 44 patients and 34 caregivers completed the questionnaires. Four patients did not complete the study due to death, lung transplantation, or transition to end-of-life care. No significant changes were observed in PROMs. However, PREMs showed significant improvements, with most scores exceeding 9/10. Patient satisfaction increased by 28% (p < 0.001), and caregiver satisfaction by 30% (p < 0.001). Caregivers of patients who did not complete the study also reported high satisfaction, comparable to that of other caregivers. Conclusions: A pragmatic and affordable tele-nursing program, based on direct phone and email consultations, may enhance patient and caregiver satisfaction in the management of pulmonary fibrosis. Full article

The weight reduction is a key objective in modern engineering, particularly in the automotive industry, to enhance vehicle performance and reduce the carbon footprint. In this context aluminum alloys are widely used in structural automotive applications, often through forging processes that enhance mechanical properties compared to the results for casting. However, the high cost of forging can limit its economic feasibility. Low pressure forging (LPF) combines the benefits of casting and forging, employing controlled pressure to fill the mold cavity and improve metal purity. This study investigates the effectiveness of the LPF process in optimizing the mechanical properties of AlSi7Mg aluminum alloy by evaluating the influence of three different magnesium content levels. The specimens underwent T6 heat treatment (solubilization treatment followed by artificial aging), with varying aging times and temperatures. Microstructural analysis and tensile tests were conducted to determine the optimal conditions for achieving superior mechanical strength, contributing to the design of lightweight, high-performance components for advanced automotive applications. The most promising properties were achieved with a T6 treatment consisting of solubilization at 540 °C for 6 h followed by aging at 180 °C for 4 h, resulting in mechanical properties of σ_y 280 MPa, σ_m 317 MPa, and A% 3.5%. Full article

The present work proposes a novel fractional-order multifunction filter topology in current-mode (CM), which is designed based on the Modified Current Feedback Operational Amplifier (MCFOA). The proposed design simultaneously generates fractional-order low-pass (FO-LPF), high-pass (FO-HPF), and band-pass (FO-BPF) outputs while utilizing an optimized set of essential active and passive elements, thereby ensuring simplicity, cost efficiency, and compatibility with integrated circuits (ICs). The fractional-order feature allows precise control over the transition slope between the passband and the stopband, enhancing design flexibility. PSpice simulations validated the filter’s theoretical performance, confirming a 1 kHz cut-off frequency, making it suitable for VLF applications such as military communication and submarine navigation. Monte Carlo analyses demonstrate robustness against parameter variations, while a low THD, a wide dynamic range, and low power consumption highlight its efficiency for high-precision, low-power applications. This work offers a practical and adaptable approach to fractional-order circuit design, with significant potential in communication, control, and biomedical systems. Full article

High-frequency (HF) injection is a widely used technique for low-speed implementation of position sensorless permanent magnet synchronous motor control. A key component of this technique is the tracking loop control system, which extracts rotor position error and utilizes proportional–integral regulation as a position observer for estimating the rotor position. Generally, this process relies on band-pass filters (BPFs) and low-pass filters (LPFs) to modulate signals in the quadrature current to obtain rotor position error information. However, limitations in filter accuracy and dynamic response lead to prolonged convergence times and timing inconsistencies in the estimation process, which affects real-time motor control performance. To address these issues, this study proposes an exponential moving average (EMA)-based scheme for rotor position error extraction, offering a rapid response under dynamic conditions such as direction reversals, step speed changes, and varying loads. EMA is used to pass the original rotor position information carried by the quadrature current signal, which contains HF components, with a specified smoothing factor. Then, after the synchronous demodulation process, EMA is employed to extract rotor position error information for the position observer to estimate the rotor position. Due to its computational simplicity and fast response in handling dynamic conditions, the proposed method can serve as an alternative to BPF and LPF, which are commonly used for rotor position information extraction, while also reducing computational burden and improving performance. Finally, to demonstrate its feasibility and effectiveness in improving rotor position estimation accuracy, the proposed system is experimentally validated by comparing it with a conventional system. Full article