Search Results (136)

Purpose: To compare the efficacy of Superb Microvascular Imaging (SMI) with grayscale ultrasound (US) and dynamic contrast-enhanced MRI in predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in invasive breast cancer. Methods: A total of 115 patients included in the study were evaluated based on their pre-treatment imaging findings (US, mammography, and MRI). Following completion of NAC, all patients underwent grayscale US and SMI examinations. In patients with available post-NAC MRI, treatment response was additionally assessed by comparing MRI findings. Imaging results were correlated with postoperative pathological outcomes, which served as the reference standard. pCR was defined as the absence of residual invasive carcinoma, regardless of ductal carcinoma in situ. Molecular subtype, Ki-67, and axillary status were recorded. Statistical analyses included chi-square tests and stepwise multiple logistic regression. Significance was set at p < 0.05 (95% CI). Results: The median age was 51 years (range: 30–75). Most tumors were high-grade (55%) and invasive ductal carcinoma (95%). Breast-pCR was achieved in 43% of patients. Significant predictors of pCR included hormone receptor negativity, HER-2 positivity, high Ki-67 expression (≥40%), non-luminal subtype, and complete radiologic response on US and MRI (p < 0.05). Lower SMI index values were strongly associated with pCR (p < 0.001), with an optimal cut-off of 1.8 demonstrating good diagnostic performance (AUC = 0.804, 95% CI: 0.721–0.887). In multivariate analysis, the combined model including US, SMI, HER-2 status, and MRI showed the highest predictive performance (AUC = 0.890, 95% CI: 0.829–0.950), explaining 55.1% of the variance in pCR. Conclusions: An SMI index < 1.8, HER-2 positivity, and complete response on US and MRI are independent predictors of pCR after NAC. Combining SMI with multimodal imaging significantly improves predictive accuracy. Full article

This study proposes a 300 W class Gallium Nitride (GaN) Solid-State Power Amplifier (SSPA)-based microwave plasma generator system for implementing next-generation light sources with high brightness and color rendering at 2.45 GHz. To overcome the lifetime limitations and control constraints of conventional magnetron systems, the proposed system introduces custom packaging technology utilizing GaN-on-SiC Bare-dies fabricated via the Win-semiconductor’s NP25 process. This approach minimizes parasitic components and significantly reduces thermal resistance compared to standard packages, ensuring reliability during high-power operation. A stable RF output of 300 W was achieved through two-stage power combining. For the plasma source, an Ar-InBr-Hg gas mixture was employed to optimize optical characteristics. This gas mixture is commonly used in electrodeless plasma lamps due to its high luminous efficacy and stable discharge characteristics. To analyze the rapid impedance discontinuity during gas ignition, numerical analysis based on the Drude model was performed, theoretically identifying the complex permittivity transition of the medium and the resulting resonant frequency up-shift mechanism. To mitigate system instability during this transition, an adaptive frequency tracking and feedback control loop based on real-time VSWR monitoring was implemented. Experimental results demonstrate precise tracking within a 100 MHz frequency variable range, achieving a system efficiency of over 53% and maintaining a VSWR below 1.15:1. These results validate the practical feasibility of GaN SSPA technology in electrodeless lighting and industrial plasma applications utilizing high-power RF energy. Full article

Aim: Sepsis-associated acute kidney injury (SA-AKI) remains a major cause of mortality, driven by inflammation and oxidative stress. Pioglitazone, a PPAR-γ agonist, has demonstrated anti-inflammatory and antioxidant effects beyond glycemic control. This study evaluated its renoprotective efficacy in a rat model of sepsis induced by cecal ligation and puncture (CLP). Methods: Thirty-six female Wistar rats were divided into Control, CLP + Saline, and CLP + Pioglitazone (10 mg/kg/day) groups. Survival was analyzed for 5 days. Renal function (BUN, creatinine, NGAL), oxidative stress (MDA), antioxidant signaling (NRF2), and inflammatory mediators (TNF-α, IL-6, HMGB1, TLR-4, NF-κB) were quantified by ELISA. Tubular epithelial necrosis, luminal debris, dilatation, hemorrhage, and inflammation were semi-quantitatively scored. Results: CLP caused marked renal dysfunction with elevated BUN, creatinine, and NGAL (p all <0.001 vs. Control). Pioglitazone significantly reduced these markers (p < 0.001 vs. CLP + Saline) and improved survival. Plasma MDA levels increased and renal Nrf2 levels decreased following CLP induction (both p < 0.001 vs. Control), whereas pioglitazone treatment significantly reduced MDA levels and increased NRF2 expression (p = 0.002 and p < 0.001 vs. CLP + Saline, respectively). Inflammatory mediators were markedly increased in sepsis (TNF-α, IL-6, HMGB1, TLR-4, and NF-κB; all p < 0.001 vs. Control) and significantly downregulated by pioglitazone (p < 0.01, p < 0.001, p < 0.001, p < 0.01, p < 0.01 vs. CLP + Saline, respectively). Histopathological injury was pronounced in septic rats (all p < 0.01 vs. Control) but was markedly ameliorated by pioglitazone p < 0.05, indicating substantial structural recovery. Conclusions: Pioglitazone markedly ameliorates CLP-induced SA-AKI by suppressing TLR-4/NF-κB/TNF-α signaling and oxidative stress, improving renal structure, function, and survival. These findings support its potential repurposing as a therapeutic adjunct in sepsis management. Full article

Display-driven optical stimuli underpin a major class of clinically validated digital therapeutics (DTx) now expanding from neuropsychiatric disorders to chronic diseases. The display’s optical characteristics—spectral power distribution, luminance, contrast, and temporal modulation—therefore define the delivered dose of these software-based interventions. In this context, blue-rich emission in the 450–480 nm band, particularly with evening exposure, can suppress melatonin via melanopsin-mediated intrinsically photo-sensitive retinal ganglion cell (ipRGC) pathways and perturb circadian timing, potentially attenuating therapeutic efficacy. This review summarizes clinical evidence for display-enabled DTx across major indications and synthesizes mechanistic and experimental data linking blue light to sleep and circadian disruption, with downstream mood, cognitive, cardiovascular, and metabolic effects, as well as increased risk of cancer and skin damage. This review distinguishes wavelength-dependent hazards by separating retinal photochemical risk in the roughly 415–450 nm range from circadian-disruptive melanopic effects in the 450–480 nm range, informing spectrum optimization for therapeutic use. It then synthesizes mitigation strategies spanning display emitter spectrum engineering, optical filtering or conversion films, and software controls such as color temperature tuning, high-frequency dimming, metameric spectrum design, and personalized circadian lighting. The review concludes with design, prescription, and standards considerations to align display output with therapeutic intent. Full article

This study aims to assess the energy efficiency of LED luminaires used in public road lighting by comparing manufacturer-declared photometric and electrical parameters with laboratory simulation results. The research also evaluates the performance of these luminaires across various road types and installation configurations to determine compliance with national and international standards. Eleven LED luminaires were tested using a rotating mirror goniophotometer in an ISO/IEC 17025-accredited laboratory. Simulations were conducted using Dialux Evo software across six road types (M1–M6) and three installation configurations (unilateral, bilateral, and staggered). Key parameters analyzed included brog (L_m), overall uniformity (U₀), longitudinal uniformity (U_l), luminous efficacy (lm/W), power factor, and total harmonic distortion (THD) in voltage and current. Discrepancies were found between manufacturer-declared and simulation results, especially in higher-class roads (M1–M3), where up to 28.57% of luminaires failed to meet the minimum luminance requirements when tested. The study highlights the importance of validating manufacturer specifications through accredited laboratory testing. Overall, LED technology improves energy efficiency in public lighting, and inconsistencies in the power factor and luminance performance suggest the need for stricter regulatory oversight and more rigorous quality control. Simulation tools like Dialux Evo prove essential for optimizing lighting designs tailored to specific road types and traffic conditions. Full article

Abdominal pain is the cardinal symptom of irritable bowel syndrome (IBS) and the primary determinant of disease burden and healthcare utilization. Despite its diagnostic centrality and high prevalence across all IBS subtypes, effective management remains a clinical challenge. This narrative review explores the pathophysiological mechanisms underlying IBS-related pain, emphasizing the role of visceral hypersensitivity, altered brain–gut communication, and luminal factors such as gas and distension. We examine current guideline recommendations, real-world treatment patterns, and evidence supporting both pharmacological and non-pharmacological interventions. Particular focus is placed on the fixed-dose combination of alverine citrate/simeticone, which targets both motor and sensory pathways. Mechanistic studies demonstrate its smooth muscle relaxant, antinociceptive, and anti-inflammatory actions. Clinical trials support its efficacy in reducing pain, improving quality of life, and lowering healthcare resource use. Despite these advances, several unmet needs remain, including subtype-specific treatment strategies, mechanistic biomarkers, and broader access to integrated care. The review concludes with a call for more personalized, mechanism-based approaches to pain management in IBS, with alverine citrate/simeticone offering a pragmatic option within this evolving therapeutic framework. Full article

Metformin, a 60-year-old biguanide and cornerstone of type 2 diabetes therapy, continues to challenge and inspire modern pharmaceutical science. Despite its chemical simplicity, metformin displays highly complex pharmacokinetic and pharmacodynamic behavior driven by transporter dependence, luminal activity, and formulation-sensitive exposure. Originally regarded as limited by low permeability and incomplete absorption, metformin has emerged as a paradigm for gut-targeted therapy, controlled- and delayed-release systems, and personalized pharmaceutics. Growing evidence has repositioned the intestine, rather than systemic plasma exposure, as a major site of action, highlighting the central role of organic cation transporters and multidrug efflux systems in determining efficacy, variability, and gastrointestinal tolerability. Beyond metabolic control, insights into transporter regulation, pharmacogenetics, microbiome interactions, and manufacturing quality have expanded metformin’s relevance as a model compound for contemporary drug development. Advances in formulation design, quality-by-design manufacturing, and regulatory control have further reinforced its clinical robustness, while repurposing efforts in oncology, immunometabolism, and regenerative medicine underscore its translational potential. This review integrates mechanistic pharmacology, formulation science, and clinical translation to position metformin not merely as an antidiabetic agent, but as a didactic model illustrating the evolution of pharmaceutics from molecule-centered design to system-oriented, precision-driven therapy. Full article

Neoadjuvant chemotherapy (NACT) is the standard treatment for muscle-invasive bladder carcinoma (MIBC), but its efficacy varies significantly among patients. The aim of this study is the identification of biomarkers and biological processes related to the response to neoadjuvant chemotherapy (NACT) in muscle-invasive bladder carcinoma (MIBC). Fifty-eight transurethral resection (TURBT) samples and thirty cystectomy samples from NACT non-responders were analyzed using mass spectrometry. Samples were classified with sparse k-means and consensus clustering. Protein networks were built using probabilistic graphical models, grouped into functional nodes, and analyzed for activity differences. Gene set enrichment analysis was applied to identify resistance mechanisms, and results were validated using The Cancer Genome Atlas (TCGA) cohort. Proteomic analysis revealed two independent classifications in TURBT samples. The first (Layer1) divided tumors into three groups, including one NACT non-responder subtype not aligned with traditional luminal or basal classifications but characterized by high expression of targetable markers NECTIN4 and Her2. The second (Layer3) separated luminal-papillary tumors from luminal-infiltrated/luminal and basal tumors. While Layer3 groups did not differ in NACT response, they showed distinct disease-free survival outcomes. Importantly, complete response to NACT was linked to improved survival in luminal subgroups but not in basal tumors, suggesting subtype-specific prognostic implications. Finally, analysis of cystectomy samples identified unique mechanisms of resistance for each subgroup, suggesting tailored therapeutic approaches. Two classification systems were defined as follows: one identified a proteomics-based non-responder group with actionable targets, and the other linked tumor subtype to prognosis. Distinct resistance mechanisms suggest opportunities for subtype-specific therapies, supporting improved management and treatment development for MIBC patients. Full article

The poor stability of CsPbBr₃ perovskite nanocrystals (PNCs) caused by weak and dynamic ligand coordination severely limits their commercial applications. Herein, a dual-ligand synergistic modification strategy based on bromocarboxylic acids (BCAs) and oleylamine (OAm) was developed to mediate the surface structures and luminescent dynamics of CsPbBr₃ PNCs. The results reveal that carboxylate groups of BCA ligands modulate crystal growth, while its terminal Br atom forms a strong coordination with exposed Pb²⁺ on the PNCs surface, which can effectively passivate lead- and bromine-related defects. The synergistic protection of OAm ligands enhances the stability of PNCs via amino-halide electrostatic interactions and steric hindrance effects. Notably, based on the relatively dense surface coating of 4-bromobutyric acid (BBA) and OAm dual-ligands, the prepared CsPbBr₃ PNCs exhibit a high photoluminescence quantum yield (PLQY) of 85.2 ± 2.4% and remarkable storage stability, retaining 90.2 ± 1.7% of their initial PL intensity after being stored for 63 days under ambient conditions. Furthermore, a prototype white light-emitting diode (WLED) fabricated with these PNCs displays a wide color gamut covering 122.1% of the NTSC standard and a luminous efficacy of 64.6 lm/W. This work provides a facile and feasible ligand engineering strategy to obtain highly stable and emissive PNCs. Full article

Mn⁴⁺-activated fluoride phosphors possess outstanding luminescent properties, making them highly suitable for applications in lighting and display technologies. However, the synthesis of such phosphors generally requires the use of large amounts of highly toxic aqueous HF, leading to serious environmental pollution. To eliminate the use of hazardous HF solution, a low-temperature molten salt method employing NH₄HF₂ was developed to synthesize the narrow-band red emitter Cs₂GeF₆: Mn⁴⁺ phosphor. Following the reaction, the product was washed with a dilute H₂O₂ solution to remove residual NH₄HF₂ and other impurities. The phase purity and morphology were analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively, and the luminescence properties were examined via photoluminescence (PL) spectroscopy. The obtained phosphors exhibit bright red emission characteristics of Mn⁴⁺ under blue-violet excitation. Among them, Cs₂GeF₆: 0.08 Mn⁴⁺ shows the highest emission intensity, with an internal quantum efficiency (IQE) of 78%. A white light-emitting diode (WLED) fabricated by combining this phosphor with a blue chip and commercial Y₃Al₅O₁₂: Ce³⁺ (YAG) phosphor achieved a high luminous efficacy (LE) of ~146 lm/W, a correlated color temperature (CCT) of ~4396 K, and a color rendering index (Ra) of ~83, alongside excellent operational color stability. Full article

Energy efficiency in road lighting is increasingly critical for sustainable urban development, yet numerical indicators essential for objective evaluation are often misunderstood or misapplied. This paper addresses fundamental misconceptions in interpreting the Power Density Indicator (PDI), a key metric for assessing lighting system efficiency. Through analysis of Romanian street lighting modernization projects and extensive literature review, we demonstrate widespread misunderstanding of PDI’s properties, including inappropriate summation across streets and failure to recognize its independence from road class. We present a comprehensive methodology for PDI interpretation and optimization through spatial visualization of Luminous Intensity Distribution Curves (LIDCs) using MATLAB’s MESH function. The theoretical framework derives minimum achievable PDI values as a function of LED-specific efficacy and system utilance. Case studies from 181 streets in Romanian cities reveal significant optimization potential. Finally, we demonstrate, through computational simulation, the theoretical ideal: a perfectly adapted LIDC achieving unitary utilance, confirming that minimum PDI depends solely on LED efficacy and optical efficiency. These findings provide practical guidance for designers to optimize energy efficiency while meeting photometric requirements. Full article

Mn⁴⁺-doped fluoride red phosphors are widely used in white LED lighting and display applications due to their excellent luminescent properties. However, their synthesis relies heavily on highly toxic aqueous hydrofluoric acid, which not only causes severe environmental and soil/water pollution but also makes it difficult to control the microstructure of the products due to the rapid reaction rate. In this study, low-melting-point NH₄HF₂ was used as the molten salt, with KMnO₄ and MnF₂ as manganese sources, to synthesize the red phosphor K₃AlF₆: Mn⁴⁺ via the molten salt method. After the reaction, impurities such as NH₄HF₂ were removed by washing with a dilute H₂O₂ solution. The microstructure, photoluminescence properties, thermal quenching behavior, and application in warm white light-emitting diodes (W-LEDs) of the K₃AlF₆: Mn⁴⁺ phosphors were investigated. The results indicate that the phosphors prepared by this method consist of a single pure phase. By adjusting the molten salt content, the morphology of the product can be transformed from nanoparticle-like to nanorod-like structures. All products exhibit the characteristic red emission of Mn⁴⁺ under blue and violet light excitation, with the optimally doped sample achieving an internal quantum efficiency (IQE) of 69% under blue light excitation. The combination of the obtained K₃AlF₆: Mn⁴⁺ with the yellow phosphor YAG enabled the fabrication of W-LEDs. These W-LEDs achieved a color rendering index (Ra) of 86.8, a luminous efficacy (LE) of 77 lm/W, and a correlated color temperature (CCT) of 3690 K, along with excellent color stability under operating conditions. Full article

Objective: This study investigates the efficacy of indocyanine green-mediated photodynamic therapy (PDT) in targeting MCF-7 breast cancer cells, a representative model of luminal A subtype, compared to healthy breast epithelial cells. Methods: MCF-7 cells and healthy breast cells were cultured in a three-dimensional (3D) hollow fiber bioreactor to mimic the tumor microenvironment in vivo. Cells were treated with ICG at concentrations ranging from 1 to 1000 μM and then photoactivated using a diode laser. Cell viability was assessed by trypan blue staining, and the production of reactive oxygen species (ROS), including singlet oxygen (¹O₂) was measured. Results: Cell viability, assessed via trypan blue exclusion, decreased dose-dependently with ICG concentrations (1–1000 μM), with MCF-7 viability dropping from 94.5% ± 0.8% at 0.1 μM to 15.83% ± 0.66% at 1000 μM, compared to healthy cells retaining >50% viability up to 500 μM (55.2% ± 2.0% at 1000 μM). Student’s t-tests confirmed significant differences (p < 0.05) between MCF-7 and control (0 μM) at all concentrations, and between MCF-7 and healthy cells, indicating selective cytotoxicity (IC₅₀: ~75 μM for MCF-7). Flow cytometry revealed MCF-7 cell concentrations were significantly lower than healthy cells’ across all ICG doses and seeding densities (p < 0.05). Spectroscopic analyses showed ICG absorption peaks at 800–900 nm, fluorescence at 800–820 nm, and singlet oxygen phosphorescence at 1270 nm, confirming effective ROS generation. Conclusions: Cell concentrations confirmed selective MCF-7 cytotoxicity (p < 0.05). Spectroscopic data validated ROS generation, supporting ICG-PDT’s potential as a selective therapy for early-stage breast cancer within a 50–500 μM therapeutic window. Full article

Postoperative recurrence (POR) in Crohn’s disease (CD) is common after intestinal resection, with over 50% developing endoscopic lesions within a year if untreated. The increasing availability of biologics and small molecules has transformed postoperative management, yet optimal strategies for prevention and treatment remain unclear. Infliximab and vedolizumab have the strongest evidence for preventing endoscopic recurrence in postoperative Crohn’s disease. Adalimumab and ustekinumab are viable alternatives supported by observational and post hoc trial data. Selective IL-23 inhibitors and JAK inhibitors have demonstrated high efficacy in moderate to severe luminal CD but lack dedicated postoperative trials. Personalized strategies, such as therapeutic drug monitoring (TDM), model informed dosing and pharmacogenetic profiling hold promise for improving long-term control of postoperative Crohn’s disease. Important gaps remain, particularly regarding the drug concentrations to target, the optimal timing for intervention, and the identification of patients most likely to benefit. Approaches that integrate disease location, clinical risk profiles, and knowledge of underlying immunopathogenic pathways could provide more precise clinical guidance. Finding molecular predictors of recurrence, directly comparing cutting-edge treatments, and integrating precision medicine techniques into standard postoperative care should be the main priorities of future research Full article

HER2-low breast cancer has been recognized as a heterogenous group of tumors influenced by hormone receptor (HR) expression, giving rise to tumors with either a luminal-like phenotype or features resembling triple-negative breast cancer (TNBC). Despite the development of HER2-targeted therapies, several studies have demonstrated their limited efficacy in patients diagnosed with HER2-low breast cancer. However, recent research has led to the development of antibody-drug conjugates (ADCs), such as trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), with the latter showing promising results in treating these patients. Despite this breakthrough, the availability of a single effective therapy fails to account for tumor heterogeneity and may contribute to the emergence of therapy resistance, leaving HER2-low patients without treatment options. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level and are capable of modulating key cellular processes. Recent studies have highlighted their potential as therapeutic targets, contributing to the advancement of personalized, patient-center therapies. In this context, the interplay between miRNAs and HER2-targeted therapies, particularly their modulation of common essential genes and signaling pathways, could reshape HER2-low therapy strategies to transform current practices aimed at improving the overall patient outcomes. Therefore, this review aims to elucidate the mechanisms underlying current HER2-targeted therapy and explore a potential crosstalk with miRNAs, ultimately serving as a guide for the development of personalized therapeutic strategies. Full article