Search Results (8,761)

With the increasing detection of artemisinin resistance to front-line antimalarials in Africa and notwithstanding the planned roll-out of RTS’S and R21 in Africa, the search for new vaccines with high efficacy remains an imperative. Towards this endeavour, we performed in silico screening to identify Plasmodium falciparum gametocyte stage genes that could be targets of protection or diagnosis. Through the analysis we identified a gene, Pf3D7_1105800, coding for a Plasmodium falciparum subtilisin-like domain-containing protein (PfSDP) and thus dubbed the gene Pfsdp. Genetic diversity assessment revealed the Pfsdp gene to be relatively conserved across continents with signs of directional selection. Using RT qPCR and Western blots, we observed that Pfsdp is expressed in all developmental stages of the parasite both at the transcript and protein level. Immunofluorescence assays found PfSDP protein co-localizing with PfMSP-1 and partially with Pfs48/45 at the asexual and sexual stages, respectively. Further, we demonstrated that anti-PfSDP peptide-specific antibodies inhibited erythrocyte invasion by 20–60% in a dose-dependent manner, suggesting that PfSDP protein might play a role in merozoite invasion. We also discovered that PfSDP protein is immunogenic in children from different endemic areas with antibody levels increasing from acute infection to day 7 post-treatment, followed by a gradual decay. The limited effect of antibodies on erythrocyte invasion could imply that it might be more involved in other processes in the development of the parasite. Full article

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article

Unmanned Aerial Vehicles (UAVs) face significant challenges in global path planning within complex terrains, as traditional algorithms (e.g., A*, PSO, APF) struggle to balance computational efficiency, path optimality, and safety. This study proposes a Voronoi–A* fusion algorithm, combining Voronoi-vertex-based rapid trajectory generation with A* supplementary expansion for enhanced performance. First, an adaptive DEM layering strategy divides the terrain into horizontal planes based on obstacle density, reducing computational complexity while preserving 3D flexibility. The Voronoi vertices within each layer serve as a sparse waypoint network, with greedy heuristic prioritizing vertices that ensure safety margins, directional coherence, and goal proximity. For unresolved segments, A* performs localized searches to ensure complete connectivity. Finally, a line-segment interpolation search further optimizes the path to minimize both length and turning maneuvers. Simulations in mountainous environments demonstrate superior performance over traditional methods in terms of path planning success rates, path optimality, and computation. Our framework excels in real-time scenarios, such as disaster rescue and logistics, although it assumes static environments and trades slight path elongation for robustness. Future research should integrate dynamic obstacle avoidance and weather impact analysis to enhance adaptability in real-world conditions. Full article

Background/Objectives: Although both the MEL90 (Carl Zeiss Meditec AG, Jena, Germany) and WaveLight EX500 (Alcon Laboratories, Inc., Fort Worth, TX, USA) are two widely used excimer lasers, comparisons between the two remain limited. This study evaluates visual and refractive outcomes from the U.S. Food and Drug Administration (FDA) premarket approval trials of these platforms in the treatment of myopia with and without astigmatism, hyperopia with and without astigmatism, and mixed astigmatism. Methods: Clinical outcomes from FDA premarket approval trials were compared between the recently approved MEL90 and the WaveLight (now termed EX500) excimer lasers. Results: A total of 714 eyes (358 patients) from MEL90 and 1353 eyes (706 patients) from EX500 were analyzed up to 6 months postoperatively. In the hyperopia/hyperopic astigmatism cohort, the EX500 demonstrated greater efficacy relative to MEL90, with more eyes achieving a postoperative uncorrected distance visual acuity (UDVA) of 20/20 or better (48.6% vs. 68.7%, respectively; p < 0.001). In both the MEL90 and EX500, at least 85% of eyes with myopia/myopic astigmatism and 68% with mixed astigmatism achieved a postoperative UDVA of 20/20 or better. For all refractive cohorts, more than 95% of eyes achieved a UDVA of 20/40 or better at 6 months (all p > 0.05). The EX500 was more likely to demonstrate an improvement of more than two lines of UDVA compared to baseline CDVA (all p < 0.05). In contrast, the MEL90 showed greater predictability of spherical equivalent within ±0.50 D and ±1.00 D for the hyperopia/hyperopic astigmatism cohort (both p = 0.007), as well as within ±0.50 D for the myopia/myopic astigmatism cohort (p < 0.001). Postoperatively, both platforms were associated with decreased glare and halos, although findings were variable in the EX500 mixed astigmatism cohort. Conclusions: Both excimer lasers demonstrated safe and effective outcomes that exceed the threshold set by the FDA. Full article

Objectives: In this research study, we introduce a novel approach to develop an innovative nanocarrier system comprising gold nanoparticles (GNPs) loaded with doxorubicin (D) in combination with natural molecules, such as trans-resveratrol (R), piperine (P), and icariin (Ic), against human cervical cancer. The final objective is to improve the anticancer efficacy of doxorubicin on HeLa and CaSki cell lines. Methods: Resveratrol was also used for the synthesis of GNP_R1 nanoparticles. Multi-functional GNPs loaded with D, R, P, and Ic (e.g., GNP_R1@D/R/P/Ic) were successfully prepared and fully characterized by SPR, TEM, HR-TEM, XRD, AFM, DLS, and zeta potential. They were investigated for in vitro stability in various biological media. The cytotoxicity activity was tested on HeLa and CaSki cell lines, using the MTT assay, for their applications as anticancer agents. Results: Our results demonstrate that the novel multi-functional GNPs (such as GNP_R1@D/R and GNP_R1@D/R/P/Ic) can effectively target the cervical cancer cells, improving the bioavailability of therapeutic agents and enhancing their cytotoxicity against cervical cancer cells. In vitro assessments demonstrated that the multi-functional GNPs exhibited improved stability and potential anticancer efficacy on human cervical cancer cells. Conclusions: The described strategy connects the benefits of biomolecules with functional nanoparticles toward the development of various GNP_R1@D/R/P/Ic nanocarriers for their applications as anticancer agents against human cervical cancer. This study provides compelling evidence that the innovative nanoparticles can enhance the therapeutic efficacy of doxorubicin against cervical cancer and offer a more advantageous alternative compared to doxorubicin monotherapy. Full article

An FR4-based X-band low phase noise oscillator loading an additional high-Q cavity resonator was designed in this study using substrate-integrated suspended line (SISL) technology. The additional resonator was coupled to an oscillator by the transmission line (coupling TL). The impact of the additional resonator on startup conditions, Q factor enhancement, and phase noise reduction was thoroughly investigated. Three oscillators loading an additional high-Q cavity resonator, loading an additional high-Q cavity resonator and performing partial dielectric extraction, and loading an original parallel feedback oscillator for comparison were presented. The experimental results showed that the proposed oscillator had a low phase noise of −131.79 dBc/Hz at 1 MHz offset from the carrier frequency of 10.088 GHz, and the FOM was −197.79 dBc/Hz. The phase noise was reduced by 1.66 dB through loading the additional resonator and further reduced by 1.87 dB through partially excising the substrate. To the best of our knowledge, the proposed oscillator showed the lowest phase noise and FOM compared with other all-FR4-based oscillators. The cost of fabrication was markedly reduced. The proposed oscillator also has the advantages of compact size and self-packaging properties. Full article

Nitrogen vacancy (NV) diamonds are promising room temperature quantum sensors. As the technology moves towards application, efficient use of energy and cost become critical for miniaturization. This work focuses on microwave-based spin control using the short-circuited end of a slot line, analyzed by finite element method (FEM) for magnetic field amplitude and uniformity. A microstrip-to-slot-line converter with a $-10$ dB bandwidth of $3.2$ GHz was implemented. Rabi oscillation measurements with an NV microdiamond on a glass fiber show uniform excitation over $1.5$ MHz across the slot, allowing spin manipulation within the coherence time of the NV center. Full article

Background/Objectives: Magnetic iron oxide nanoparticles (IONPs), human serum albumin (HSA) and folic acid (FA) are prospective components for hybrid nanosystems for various biomedical applications. The magnetic nanosystems FA-HSA@IONPs (FAMs) containing IONPs, HSA, and FA residue are engineered in the study. Methods: Composition, stability and integrity of the coating, and peroxidase-like activity of FAMs are characterized using UV/Vis spectrophotometry (colorimetric test using o-phenylenediamine (OPD), Bradford protein assay, etc.), spectrofluorimetry, dynamic light scattering (DLS) and electron magnetic resonance (EMR). The selectivity of the FAMs accumulation in cancer cells is analyzed using flow cytometry and confocal laser scanning microscopy. Results: FAMs (d_N~55 nm by DLS) as a drug delivery platform have been administered to cancer cells (human breast adenocarcinoma MCF-7 and MDA-MB-231 cell lines) in vitro. Methylene blue, as a model photosensitizer, has been non-covalently bound to FAMs. An increase in photoinduced cytotoxicity has been found upon excitation of the photosensitizer bound to the coating of FAMs compared to the single photosensitizer at equivalent concentrations. The suitability of the nanosystems for photodynamic therapy has been confirmed. Conclusions: FAMs are able to effectively enter cells with increased folate receptor expression and thus allow antitumor photosensitizers to be delivered to cells without any loss of their in vitro photodynamic efficiency. Therapeutic and diagnostic applications of FAMs in oncology are discussed. Full article

This paper presents a highly linear one-bit loaded-line phase shifter that leverages PIN diodes in combination with a coupler-based impedance transformer. The proposed phase shifter adopts a loaded-line topology, where PIN diodes are configured in a parallel-to-ground arrangement to improve linearity performance. To further enhance linearity, a coupler-based impedance transformer is employed to reduce the impedance seen by each PIN diode, thereby minimizing nonlinear behavior. To demonstrate the effectiveness of this design, a one-bit digital phase shifter is developed, simulated, and fabricated to achieve a 45-degree phase shift at 2 GHz. Experimental measurements confirm an input third-order intercept point (IIP3) exceeding 100 dBm under a range of test conditions, validating the proposed architecture’s linearity advantages. Full article

Urban environments present substantial obstacles to GPS positioning accuracy, primarily due to multipath interference and limited satellite visibility. To address these challenges, we propose a novel weighting approach, referred to as the HK model, that enhances real-time GPS positioning performance by leveraging the variability of the signal-to-noise ratio (SNR), without requiring auxiliary sensors. Analysis of 24 h observational datasets collected across diverse environments, including open-sky (OS), city streets (CS), and urban canyons (UC), demonstrates that multipath-affected non-line-of-sight (NLOS) signals exhibit significantly greater SNR variability than direct line-of-sight (LOS) signals. The HK model classifies received signals based on the standard deviation of their SNR and assigns corresponding weights during position estimation. Comparative performance evaluation indicates that relative to existing weighting models, the HK model improves 3D positioning accuracy by up to 22.4 m in urban canyon scenarios, reducing horizontal RMSE from 13.0 m to 4.7 m and vertical RMSE from 19.5 m to 6.9 m. In city street environments, horizontal RMSE is reduced from 11.6 m to 3.8 m. Furthermore, a time-sequential analysis at the TEHE site confirms consistent improvements in vertical positioning accuracy across all 24-hourly datasets, and in terms of horizontal accuracy, in 22 out of 24 cases. These results demonstrate that the HK model substantially surpasses conventional SNR- or elevation-based weighting techniques, particularly under severe multipath conditions frequently encountered in dense urban settings. Full article

Background/Objectives: X-ray computed tomography (XCT) is a powerful tool for volumetric imaging, where three-dimensional (3D) images are generated from a large number of individual X-ray projection images. However, collecting the required number of low-noise projection images is time-consuming, limiting its applicability to scenarios requiring high temporal resolution, such as the study of dynamic processes. Inspired by stereo vision, we previously developed stereo X-ray imaging methods that operate with only two X-ray projections, enabling the 3D reconstruction of point and line fiducial markers at significantly faster temporal resolutions. Methods: Building on our prior work, this paper demonstrates the use of stereo X-ray techniques for 3D reconstruction of sharp object corners, eliminating the need for internal fiducial markers. This is particularly relevant for deformation measurement of manufactured components under load. Additionally, we explore model training using synthetic data when annotated real data is unavailable. Results: We show that the proposed method can reliably reconstruct sharp corners in 3D using only two X-ray projections. The results confirm the method’s applicability to real-world stereo X-ray images without relying on annotated real training datasets. Conclusions: Our approach enables stereo X-ray 3D reconstruction using synthetic training data that mimics key characteristics of real data, thereby expanding the method’s applicability in scenarios with limited training resources. Full article

Background and Clinical Significance: Serratus Anterior Muscle Pain Syndrome (SAMPS) is an underdiagnosed cause of anterior chest wall pain, often attributed to myofascial trigger points of the serratus anterior muscle (SAM) or dysfunction of the Long Thoracic Nerve (LTN), leading to significant disability and affecting ipsilateral upper limb movement and quality of life. Current diagnosis relies on exclusion and physical examination, with limited treatment options beyond conservative approaches. This case report presents a novel approach to chronic SAMPS, successfully diagnosed using Sonoguided Digital Palpation (SDP) and treated with ultrasound-guided hydrodissection of the LTN using 5% dextrose in water (D5W) without local anesthetic (LA), in a patient where conventional treatments had failed. Case Presentation: A 72-year-old male presented with a three-year history of persistent left chest pain radiating to the upper back, exacerbated by activity and mimicking cardiac pain. His medical history included two percutaneous coronary interventions. Physical examination revealed tenderness along the anterior axillary line and a positive hyperirritable spot at the mid axillary line at the 5th rib level. SDP was used to visualize the serratus anterior fascia (SAF) and LTN, and to reproduce the patient’s concordant pain by palpating the LTN. Ultrasound-guided hydrodissection of the LTN was then performed using 20–30cc of D5W without LA to separate the nerve from the surrounding tissues, employing a “fascial unzipping” technique. The patient reported immediate pain relief post-procedure, with the pain reducing from 9/10 to 1/10 on the Numeric Rating Scale (NRS), and sustained relief and functional improvement at the 12-month follow-up. Conclusions: Sonoguided Digital Palpation (SDP) of the LTN can serve as a valuable diagnostic adjunct for visualizing and diagnosing SAMPS. Ultrasound-guided hydrodissection of the LTN with D5W without LA may provide a promising and safe treatment option for patients with chronic SAMPS refractory to conservative management, resulting in rapid and sustained pain relief. Further research, including controlled trials, is warranted to evaluate the long-term efficacy and generalizability of these findings and to compare D5W to other injectates. Full article

Background: There has been a reduction in successful H. pylori eradication rates recently, which is largely attributed to increasing antibiotic resistance. In areas of high dual clarithromycin and metronidazole resistance such as ours, Maastricht VI/Florence guidelines recommend bismuth quadruple therapy (BQT) as first line of therapy; however, the availability of bismuth was poor in Ireland until recently. Similarly, tetracycline, a component of BQT, is restricted locally, with doxycycline (D) being approved and reimbursed for most indications. Aims: To assess the efficacy of BQT-D therapy for H. pylori eradication in an Irish cohort. Methods: All patients testing positive for H. pylori in three Irish referral centres by urea breath test, stool antigen, or histology were treated prospectively with BQT-D (bismuth subcitrate 120 mg QDS, metronidazole 400 mg TDS, doxycycline 100 mg BD and esomeprazole 40 mg BD) for 14 days. Eradication was evaluated with a urea breath test (UBT) >4 weeks after therapy cessation or by stool antigen testing, as available. Outcomes were recorded and analysed according to demographics and H. pylori treatment history of the patients. Results: 217 patients completed post-eradication testing. Of which, 124 (57%) were female, with a mean age 52 years. 180 patients (83%) were treatment-naïve. A total of 165/180 (92%) of the treatment-naïve patients had successful eradication. There was no association between eradication and gender or age in this cohort (p = 0.3091, p = 0.962 respectively). A total of 29 patients received this therapy as second-line therapy, of which 22 (76%) had successful eradication. Eight patients received the regimen as rescue therapy, with seven (88%) having successful eradication. No serious adverse events were reported. Eleven individuals (6.5%) commented on the complicated nature of the regimen, with 11 tablets being taken at five intervals daily. Conclusions: BQT-D as first-line therapy for H. pylori infection is highly effective in a high dual-resistance population, achieving >90% eradication. BQT-D as a second-line treatment performed less well. Our data support BQT-D as a first-line treatment. Full article

With their superior switching speed, GaN high-electron-mobility transistors (HEMTs) enable high power density, reduce energy losses, and increase power efficiency in a wide range of applications, such as power electronics, due to their high breakdown voltage. GaN-HEMT devices are subject to long-term reliability due to the self-heating effect and lattice mismatch between the SiC substrate and the GaN. Depletion-mode GaN HEMTs are utilized for radio frequency applications, and this work investigates three wide-bandgap (WBG) GaN HEMT fixed-frequency oscillators with output buffers. The first GaN-on-SiC HEMT oscillator consists of an HEMT amplifier with an LC feedback network. With the supply voltage of 0.8 V, the single-ended GaN oscillator can generate a signal at 8.85 GHz, and it also supplies output power of 2.4 dBm with a buffer supply of 3.0 V. At 1 MHz frequency offset from the carrier, the phase noise is −124.8 dBc/Hz, and the figure of merit (FOM) of the oscillator is −199.8 dBc/Hz. After the previous study, the hot-carrier stressed RF performance of the GaN oscillator is studied, and the oscillator was subject to a drain supply of 8 V for a stressing step time equal to 30 min and measured at the supply voltage of 0.8 V after the step operation for performance benchmark. Stress study indicates the power oscillator with buffer is a good structure for a reliable structure by operating the oscillator core at low supply and the buffer at high supply. The second balanced oscillator can generate a differential signal. The feedback filter consists of a left-handed transmission-line LC network by cascading three unit cells. At a 1 MHz frequency offset from the carrier of 3.818 GHz, the phase noise is −131.73 dBc/Hz, and the FOM of the 2nd oscillator is −188.4 dBc/Hz. High supply voltage operation shows phase noise degradation. The third GaN cross-coupled VCO uses 8-shaped inductors. The VCO uses a pair of drain inductors to improve the Q-factor of the LC tank, and it uses 8-shaped inductors for magnetic coupling noise suppression. At the VCO-core supply of 1.3 V and high buffer supply, the FOM at 6.397 GHz is −190.09 dBc/Hz. This work enhances the design techniques for reliable GaN HEMT oscillators and knowledge to design high-performance circuits. Full article

This study investigates the effects of copper nanoparticles (CuNPs) on KRT19 gene expression in four breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF7, and T47D), representing triple-negative and luminal subtypes. Using cytotoxicity assays, quantitative RT-PCR, and bioinformatics tools (STRING, g:Profiler), we demonstrate subtype-specific, dose-dependent KRT19 suppression, with epithelial-like cell lines showing greater sensitivity. CuNPs, characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) with a mean size of 179 ± 15 nm, exhibited dose-dependent cytotoxicity. Bioinformatics analyses suggest KRT19′s potential as a biomarker for CuNP-based therapies, pending in vivo and clinical validation. These findings highlight CuNPs’ therapeutic potential and the need for further studies to optimize their application in personalized breast cancer treatment. Full article