Search Results (311)

Background: Charcot–Marie–Tooth (CMT) is a group of inherited diseases impairing the peripheral nervous system. CMT originates from genetic variants that affect proteins fundamental for the myelination of peripheral nerves and survival. Moreover, environmental and humoral factors can impact disease development and evolution. Currently, no therapy is available. Metabolomics is an emerging field of biomedical research that enables the development of novel biomarkers for neurodegenerative diseases by targeting metabolic pathways or metabolites. This study aimed to evaluate the metabolomics profile of CMT disease by comparing patients with healthy individuals. Methods: A total of 22 CMT patients (CMT) were included in this study and were demographically matched with 26 healthy individuals (C). Serum samples were analyzed through Nuclear Magnetic Resonance spectroscopy, and multivariate and univariate statistical analyses were subsequently applied. Results: A supervised model showed a clear separation (R²X = 0.3; R²Y = 0.7; Q² = 0.4; p-value = 0.0004) between the two classes of subjects, and nine metabolites were found to be significantly different (2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate). The combined ROC curve showed an AUC of 0.94 (CI: 0.9–1). Additional altered metabolic pathways were also identified within the disease context. Conclusion: This study represents a promising starting point, demonstrating the efficacy of metabolomics in evaluating CMT patients and identifying novel potential disease biomarkers. Full article

Background/Objectives: Tegoprazan (TPZ) is a potassium-competitive acid blocker (P-CAB) used to treat conditions such as gastroesophageal reflux disease, peptic ulcer, and Helicobacter pylori infection. It exists in three solid forms: amorphous, Polymorph A, and Polymorph B. This study investigates the molecular basis of polymorph selection, focusing on conformational bias and solvent-mediated phase transformations (SMPTs). Methods: The conformational energy landscapes of two TPZ tautomers were constructed using relaxed torsion scans with the OPLS4 force field and validated by nuclear Overhauser effect (NOE)-based nuclear magnetic resonance (NMR). Hydrogen-bonded dimers were analyzed using DFT-D. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), solubility, and slurry tests were conducted using methanol, acetone, and water. Kinetic profiles were modeled with the Kolmogorov–Johnson–Mehl–Avrami (KJMA) equation. Results: Polymorph A was thermodynamically stable across all analyses. Both amorphous TPZ and Polymorph B converted to A in a solvent-dependent manner. Methanol induced direct A formation, while acetone showed a B → A transition. Crystallization was guided by solution conformers and hydrogen bonding. Conclusions: TPZ polymorph selection is governed by solution-phase conformational preferences, tautomerism, and solvent-mediated hydrogen bonding. DFT-D and NMR analyses showed that protic solvents favor the direct crystallization of stable Polymorph A, while aprotic solvents promote the transient formation of metastable Polymorph B. Elevated temperatures and humidity accelerate polymorphic transitions. This crystal structure prediction (CSP)-independent strategy offers a practical framework for rational polymorph control and the mitigation of disappearing polymorph risks in tautomeric drugs. Full article

(1) Background: A severe decline in knee joint function significantly affects the mobility of the elderly, making it a key concern in the field of geriatric health. To alleviate the pressure on the knee joints of the elderly during daily movements such as sitting and standing, effective biomechanical solutions are required. (2) Methods: In this study, a biomechanical framework was established based on mechanical analysis to derive the transfer relationship between the ground reaction force and the knee joint moment. Experiments were designed to collect knee joint data on the elderly during the sit-to-stand process. Meanwhile, magnetic resonance imaging (MRI) images were processed through a medical imaging control system to construct a detailed digital 3D knee joint model. A finite element analysis was used to verify the model to ensure the accuracy of its structure and mechanical properties. An improved radial basis function was used to fit the pressure during the entire sit-to-stand conversion process to reduce the computational workload, with an error of less than 5%. In addition, a small-target human key point recognition network was developed to analyze the image sequences captured by the camera. The knee joint angle and the knee joint pressure distribution during the sit-to-stand conversion process were mapped to a three-dimensional interactive platform to form a digital twin system. (3) Results: The system can effectively capture the biomechanical behavior of the knee joint during movement and shows high accuracy in joint angle tracking and structure simulation. (4) Conclusions: This study provides an accurate and comprehensive method for analyzing the biomechanical characteristics of the knee joint during the movement of the elderly, laying a solid foundation for clinical rehabilitation research and the design of assistive devices in the field of rehabilitation medicine. Full article

Background and Objectives: Dental adhesives augmented with magnetic nanoparticles (MNPs) have been proposed to prevent microleakages. MNPs dispersed in a dental adhesive reduce the thickness of the adhesive layer applied in a magnetic field and enhance the bond strength by favoring the penetration of the adhesive into dentinal tubules. However, the restoration’s color has been found to be affected by the MNPs. This study tests the hypothesis that MNP coating can alleviate the esthetic impact of magnetic dental adhesives. Materials and Methods: We synthesized Fe₃O₄ MNPs with silica coating (MNPs-SiO₂), calcium-based coating (MNPs-Ca), and no coating. Their morphology was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Their chemical composition was assessed by energy-dispersive X-ray spectroscopy (EDX), and magnetic properties were measured using a vibrating sample magnetometer. FTIR spectroscopy was used to evaluate the polymerization of the MNP-laden adhesive. We prepared cavities in molar phantoms divided in four groups (n = 15 each) restored using the same adhesive with different MNP contents: Group 0 (G0)—no MNPs, G1—MNPs-SiO₂, G2—MNPs-Ca, and G3—uncoated MNPs. The restoration’s color was quantified in the CIELAB color space using a dental spectrophotometer. Results: MNPs-SiO₂ were globular, whereas MNPs-Ca had a cubic morphology. The SiO₂ layer was 73.1 nm ± 9.9 nm thick; the Ca(OH)₂ layer was 19.97 nm ± 2.27 nm thick. The saturation magnetization was 18.6 emu/g for MNPs-SiO₂, 1.0 emu/g for MNPs-Ca, and 65.7 emu/g for uncoated MNPs. MNPs had a marginal effect on the adhesive’s photopolymerization. The mean color difference between G0 and G2 was close to the 50:50% acceptability threshold, whereas the other groups were far apart from G0. The mean whiteness index of G2 did not differ significantly from that of G0; G1 deviated marginally from G0, whereas G3 differed significantly from G0. Conclusions: These results suggest that MNP coating can mitigate the influence of MNP-laden dental adhesives on the color of restorations. Full article

A four-vector potential of an external test electromagnetic field in a Schwarzschild background is described in terms of a combination of dipole and quadrupole magnetic fields. This combination is an interior solution of the source-free Maxwell equations. Such external test magnetic fields cause the dynamics of charged particles around the black hole to be nonintegrable, and are mainly responsible for chaotic dynamics of charged particles. In addition to the external magnetic fields, some circumstances should be required for the onset of chaos. The effect of the magnetic fields on chaos is shown clearly through an explicit symplectic integrator and a fast Lyapunov indicator. The inclusion of the quadrupole magnetic fields easily induces chaos, compared with that of the dipole magnetic fields. This result is because the Lorentz forces from the quadrupole magnetic fields are larger than those from the dipole magnetic fields. In addition, the Lorentz forces act as attractive forces, which are helpful for bringing the occurrence of chaos in the nonintegrable case. Full article

Background: Invasive and non-invasive neuromodulation in psychiatry represents a burgeoning field that leverages advanced neuromodulation techniques to address substance use disorders (SUDs). Aims: This narrative review synthesizes findings from multiple reviews to evaluate the efficacy of neuromodulation in treating SUDs. Methods: A comprehensive literature search was conducted between December 2024 and April 2025, focusing on systematic reviews and meta-analyses that examined various neuromodulation modalities, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). The selected reviews were analyzed to identify common themes, outcomes, and gaps in the current understanding of these treatments for SUDs. Results: 11 reviews met the final inclusion criteria; 5 focused on non-invasive neuromodulation (rTMS, tDCS) and 6 on invasive neuromodulation (DBS). Non-invasive neurostimulation was associated with modest improvements in craving and cognitive dysfunction in individuals with SUDs. Similarly, invasive neuromodulation (DBS), through high-frequency stimulation of the bilateral nucleus accumbens, appeared to reduce cravings and improve comorbid psychiatric symptoms in both preclinical and human studies. Importantly, small sample sizes, heterogeneity in targets and stimulation protocols, and short follow-up periods significantly limit the generalizability of current findings from both non-invasive and invasive neuromodulation studies. Conclusions: As novel and more effective therapies for the treatment of SUD are desperately needed, procedural interventional psychiatry holds promise. However, despite encouraging results, existing evidence is still preliminary, and larger, rigorously designed studies are warranted to further establish the safety and efficacy of neuromodulatory interventions for SUD treatment. Full article

Background: Nanomedicine approaches for cancer therapy face significant challenges, including a poor tumor accumulation, limited therapeutic efficacy, and systemic toxicity. We hypothesized that controlling the clustering of poly(acrylic acid-co-maleic acid) (PAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) would enhance their magnetic properties for improved targeting, while enabling a pH-responsive drug release in tumor microenvironments. Methods: PAM-stabilized SPION clusters were synthesized via arrested precipitation, characterized for physicochemical and magnetic properties, and evaluated for doxorubicin loading and pH-dependent release. A dual targeting approach combining antibody conjugation with magnetic guidance was assessed in cellular models, including a novel alternating magnetic field (AMF) pre-treatment protocol. Results: PAM-SPION clusters demonstrated controlled size distributions (60–100 nm), excellent colloidal stability, and enhanced magnetic properties, particularly for larger crystallites (13 nm). The formulations exhibited a pH-responsive drug release (8.5% at pH 7.4 vs. 14.3% at pH 6.5) and a significant enhancement of AMF-triggered release (17.5%). The dual targeting approach achieved an 8-fold increased cellular uptake compared to non-targeted formulations. Most notably, the novel AMF pre-treatment protocol demonstrated an 87% improved therapeutic efficacy compared to conventional post-treatment applications. Conclusions: The integration of targeting antibodies, magnetic guidance, and a pH-responsive PAM coating creates a versatile theranostic platform with significantly enhanced drug delivery capabilities. The unexpected synergistic effect of the AMF pre-treatment represents a promising new approach for improving the therapeutic efficacy of nanoparticle-based cancer treatments. Full article

Belle II is a particle physics experiment working at an high luminosity collider within a hard irradiation environment. The Time-Of-Propagation detector, aimed at the charged particle identification, surrounds the Belle II tracking detector on the barrel part. This detector is composed by 16 modules, each module contains a finely fused silica bar, coupled to microchannel plate photomultiplier tube (MCP-PMT) photo-detectors and readout by high-speed electronics. The MCP-PMT lifetime at the nominal collider luminosity is about one year, this is due to the high photon background degrading the quantum efficiency of the photocathode. An alternative to these MCP-PMTs is multi-pixel photon counters (MPPC), known as silicon photomultipliers (SiPM). The SiPMs, in comparison to MCP-PMTs, have a lower cost, higher photon detection efficiency and are unaffected by the presence of a magnetic field, but also have a higher dark count rate that rapidly increases with the integrated neutron flux. The dark count rate can be mitigated by annealing the damaged devices and/or operating them at low temperatures. We tested SiPMs, with different dimensions and pixel sizes from different producers, to study their time resolution (the main constraint that has to satisfy the photon detector) and to understand their behavior and tolerance to radiation. For these studies we irradiated the devices to radiation up to $5\times {10}^{11}1$ MeV neutrons equivalent (neq) per cm² fluences; we also started studying the effect of annealing on dark count rates. We performed several measurements on these devices, on top of the dark count rate, at different conditions in terms of overvoltage and temperatures. These measurements are: IV-curves, amplitude spectra, time resolution. For the last two measurements we illuminated the devices with a picosecond pulsed laser at very low intensities (with a number of detected photons up to about twenty). We present results mainly on two types of SiPMs. A new SiPM prototype developed in collaboration with FBK with the aim of improving radiation hardness, is expected to be delivered in September 2025. Full article

Background: The increasing use of technologies operating between 10 and 200 kHz, such as RFID, wireless power transfer systems, and induction cooktops, raises concerns about electromagnetic interference (EMI) with cardiac implantable electronic devices (CIEDs). The mechanisms of interaction within this frequency range have been only partially addressed by both the scientific and regulatory communities. Methods: A physical twin of a pacemaker/implantable defibrillator (PM/ICD) was developed to experimentally assess voltages induced at the input stage by low-to-mid-frequency magnetic fields. The setup simulates the two sensing modalities programmable in PMs/ICDs and allows for the analysis of different implant configurations, lead geometries, and positions within a human body phantom. Results: Characterization of the physical twin demonstrated its capability to reliably measure induced voltages in the range of 5 mV to 1.5 V. Its application enabled the identification of factors beyond the implant’s induction area that contribute to the induced voltage, such as the electrode-tissue interface and body-induced currents. Conclusions: This physical twin represents a valuable tool for experimentally validating the mechanisms of EMI in CIEDs, providing insights beyond current standards. The data obtained can serve as a reference for the validation of numerical models and patient-specific digital twins. Moreover, it offers valuable information to guide future updates and revisions of international electromagnetic compatibility standards for CIEDs. Full article

With the evolution of magnetic devices toward structural innovation and high reliability, the traditional design methods, such as size optimization and shape optimization, are limited by preset structural forms, making it challenging to generate novel structures and topologies. Topology-optimized design methods can achieve an optimal distribution of constituent materials of magnetic devices by optimizing the objective performance subject to certain constraints, and can provide greater freedom for designers. Based on the above background, this paper firstly investigates the principles of deterministic topology optimization methods, and introduces the latest specific applications in magnetic devices. It also demonstrates the advantages of topology optimization technology in enhancing operating performance, fostering structural innovation, and improving material utilization in magnetic devices. To manage uncertainties in design and manufacturing processes of magnetic devices, this paper analyzes uncertainty topology optimization methods, respectively, reliability and robustness-based topology optimization algorithms. To facilitate manufacturing, this paper summarizes the filter strategy for the new structure obtained by topology optimization. Finally, the problems faced by the topology optimization method in the field of magnetic devices are discussed, and a future development direction is projected. Full article

Papapetrou showed that the covariant derivative of a Killing vector field satisfies Maxwell’s equations in vacuum. Papapetrou’s result is extended, in this article, and it is shown that the covariant derivative of a Killing vector field satisfies Maxwell’s equations in non-vacuum backgrounds as well if one allows electromagnetic currents of purely geometric origin. It is then postulated that every Killing vector field gives rise to a physical electromagnetic field and, in a non-vacuum background, a physical electromagnetic current—hereafter called Killing electromagnetic field and Killing electromagnetic current, respectively. It is shown that the Killing electromagnetic field of the flat FLRW (Friedmann–Lema$\hat{\mathrm{i}}$tre–Robertson–Walker) universe comprises a Killing magnetic field and a rotational Killing electric field; an upper bound on the Killing magnetic field is derived, and it is found that the upper bound is consistent with the current observational bounds on the cosmic magnetic field. Next, the time-like Killing vector of the Schwarzschild spacetime is shown to give rise to a radial Killing electric field. It is also shown that in the weak field regime—and far from the matter distribution—the back reaction of the radial Killing electric field changes the Schwarzschild metric to the Reissner–Nordström metric, establishing a partial converse of Wald’s result. Drawing upon Rainich’s work on Rainich–Riemann manifolds, the etiological question of how a physical electromagnetic field can arise out of geometry is discussed; it is also argued that detection of the Killing electric field of flat FLRW spacetime may be within the current experimental reach. Finally, this article discusses the relevance of Killing electromagnetic currents and the aforementioned transmutation of Schwarzschild spacetime to Reissner–Nordstrom spacetime, to Misner and Wheeler’s program of realizing “charge without charge”. Full article

Background/Objectives: Assessment of the hemodynamic status of the brain in patients with cerebrovascular diseases is crucial for providing valuable clinical information. Various magnetic resonance perfusion sequences are used in studies, and one of the current challenges is comparing methods utilizing exogenous and endogenous contrast. This meta-analysis aimed to evaluate the correlation between arterial spin labeling (ASL)-derived perfusion parameters and those obtained by dynamic susceptibility contrast (DSC) perfusion in stroke and steno-occlusive diseases. Methods: A systematic review and meta-analysis were conducted, including 14 studies that reported correlation coefficients between perfusion MRI sequences in the assessment of stroke or steno-occlusive diseases. The correlation between ASL-derived cerebral blood flow (ASL-CBF) and DSC-derived cerebral blood flow (DSC-CBF) was analyzed, considering different magnetic field strengths (1.5 T and 3.0 T), sequence types, and brain regions. Additionally, real and normalized data were compared. Results: A moderate positive correlation was found between ASL-CBF and DSC-CBF (R = 0.464). Subgroup analysis demonstrated that ASL-CBF and DSC-CBF correlated at 3.0 T (R = 0.401) and 1.5 T (R = 0.700). No significant differences were observed in correlation coefficients based on sequence type or brain region. Normalized data demonstrated a higher correlation coefficient compared to real data (Rreal = 0.393, Rnorm = 0.496). Additionally, the correlation coefficient between ASL-CBF and DSC-derived mean transit time (DSC-MTT) for all included studies was R = −0.422. Conclusions: ASL-derived perfusion parameters demonstrate moderate-to-high agreement with DSC perfusion parameters in stroke and steno-occlusive patients. These findings support the potential utility of ASL as a non-invasive alternative to DSC perfusion imaging in clinical and research settings. Full article

Background: Glioblastoma (GBM) resists current therapies due to its rapid proliferation, diffuse invasion, and heterogeneous cell populations. We previously showed that a single cold atmospheric plasma discharge tube (DT) reduces GBM viability via broad-spectrum electromagnetic (EM) emissions. Here, we tested whether two DTs arranged in a helmet configuration could generate overlapping EM fields to amplify the anti-tumor effects without thermal injury. Methods: The physical outputs of the single- and dual-DT setups were characterized by infrared thermography, broadband EM field probes, and oscilloscope analysis. Human U87-MG cells were exposed under the single or dual configurations. The viability was quantified with WST-8 assays mapped across 96-well plates; the intracellular reactive oxygen species (ROS), membrane integrity, apoptosis, and mitochondrial potential were assessed by multiparametric flow cytometry. Our additivity models compared the predicted versus observed dual-DT cytotoxicity. Results: The dual-DT operation produced constructive EM interference, elevating electric and magnetic field amplitudes over a broader area than either tube alone, while temperatures remained <39 °C. The single-DT exposure lowered the cell viability by ~40%; the dual-DT treatment reduced the viability by ~60%, exceeding the additive predictions. The regions of greatest cytotoxicity co-localized with the zones of highest EM field overlap. The dual-DT exposure doubled the intracellular ROS compared with single-DT and Annexin V positivity, confirming oxidative stress-driven cell death. The out-of-phase operation of the discharge tubes enabled the localized control of the treatment regions, which can guide future treatment planning. Conclusions: Two synchronously operated plasma discharge tubes synergistically enhanced GBM cell killing through non-thermal mechanisms that coupled intensified overlapping EM fields with elevated oxidative stress. This positions modular multi-DT arrays as a potential non-invasive adjunct or alternative to existing electric-field-based therapies for glioblastoma. Full article

Background: The main mechanism of optic nerve damage in patients with pituitary adenoma (PA) is the pressure of optic chiasm. The retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL)+, and GCL++ thickness measurement by optical coherence tomography (OCT), visual function evaluation, and magnetic resonance imaging (MRI) can be used to predict visual function recovery. In our study, we investigated the associations between visual acuity (VA), visual field (VF), RNFL, GCL changes, and the findings of MRI in patients with PA. Methods: This study was conducted in the Departments of Ophthalmology and Neurosurgery of the Lithuanian University of Health Sciences Hospital. A total of 25 patients diagnosed with PA were included in the study group, and 27 healthy subjects were included in the control group. The thickness of the RNFL and ganglion cell layer (GCL+, GCL++) and optic nerve disc diameter was analysed with OCT. Moreover, an MRI was performed for patients with PA. Results: The RNFL thickness around the optic disk measured preoperatively was reduced significantly in the temporal quadrant in PA patients compared with the control group (median (min; max); mean rank: 73.5 (52; 109); 58.39 vs. 69.5 (16; 168); 46.14; p = 0.038). We found that it was reduced significantly only in the inferior quadrant of the macro-PA group compared to the micro-PA group (median (min; max); mean rank: 99.5 (61; 115); 21.07 vs. 106.5 (90; 121); 32.15), p = 0.008, respectively). The RNFL thickness was reduced significantly only in the inferior quadrant of the non-active PA group compared to the active PA group (median (min; max); mean rank: 118.5 (49; 144); 17.42 vs. 130.5 (77; 156); 28.05), p = 0.028, respectively). RNFL thickness was reduced significantly only in the temporal quadrant in the PA with suprasellar extension group compared to the PA without suprasellar extension group (median (min; max); mean rank: 67.5 (16; 99); 21.66 vs. 72 (58; 168); 30.39), p = 0.036, respectively). Furthermore, GCL++ thickness was reduced significantly in total and in superior and inferior sectors of the PA with suprasellar extension group compared to the PA without suprasellar extension group (median (min; max); mean rank: 98.5 (57; 113); 21.8; 101 (61; 121); 21.48 and 102.5 (59; 116); 21.71 vs. 103.5 (95; 115); 30.2; 106.5 (90; 115); 30.61 and 104.5 (95; 113); 30.32), p = 0.043; p = 0.028 and p = 0.038, respectively). In the control group, significant positive correlations were found between optic disc area and the total RNFL thickness (r = 0.440, p < 0.001). In the PA group, significant correlations were observed between optic rim area and total RNFL thickness (r = 0.493, p < 0.001) and all quadrants, with the strongest in the nasal quadrant (r = 0.503, p < 0.001). A moderate to strong negative correlation was found between visual field (VF) defects and RNFL thickness, with the strongest correlation observed in the superior quadrant. Conclusions: OCT offers a detailed insight into the microscopic structural and functional changes throughout the entire visual pathway in patients with PA. Our findings demonstrate a significant negative correlation between RNFL thickness and visual field defects, highlighting the clinical relevance of OCT measurements in visual function assessment. Moreover, the results suggest that optic rim area may be a more reliable indicator of RNFL thickness variations than optic disc area in patients with PA. Full article

The Forbush effects (FEs) in cosmic rays associated with interplanetary disturbances caused by the disappearance of solar filaments (DSFs) outside active regions (ARs) are considered. In total, 481 FEs were detected for 1995–2023 using the database of Forbush Effects and Interplanetary Disturbances (FEID). The behavior of the cosmic ray density was calculated using the Global Survey Method (GSM). The distributions of the FE numbers depending on their duration and magnitude, as well as on the characteristics of the interplanetary and near-Earth medium, were obtained. It is found that the average duration of such FEs (33.4 ± 0.5 h) is almost the same as for events associated with CMEs from ARs, but the average magnitude is much smaller (0.83 ± 0.03%). It is also shown that coronal mass ejections (CMEs) caused by DSFs are often low-speed interplanetary disturbances (with an average maximum SW speed of 423.2 ± 3.5 km/s), the velocities of which are close to the speed of the background solar wind (SW). During FEs associated with CMEs after DSFs outside ARs, on average, unsettled geomagnetic activity is observed. Magnetic storms were recorded only in 19% of events. Lower values of FE magnitude and geomagnetic activity are associated with weakened magnetic fields and low speeds of such interplanetary disturbances. Full article