We considered the generation of gravitational waves by the binary system associated with a wormhole. In the Newtonian limit, the gravitational potential of a wormhole requires the effective mass of ...the wormhole taking into account radial tension effects. This definition allows us to derive gravitational wave production in homogeneous and heterogeneous binary systems. Therefore, we studied gravitational waves generation by orbiting wormhole–wormhole and wormhole–black hole binary systems before coalescence. Cases involving negative mass require more careful handling. We also calculated the energy loss to gravitational radiation by a particle orbiting around the wormhole and by a particle moving straight through the wormhole mouth, respectively.
Regenerative medicine is targeted to improve, restore or replace damaged tissues or organs using a combination of cells, materials and growth factors. Both tissue engineering and developmental ...biology currently deal with the process of tissue self-assembly and extracellular matrix (ECM) deposition. In this investigation, additive manufacturing (AM) with a multihead deposition system (MHDS) was used to fabricate three-dimensional (3D) cell-printed scaffolds using layer-by-layer (LBL) deposition of polycaprolactone (PCL) and chondrocyte cell-encapsulated alginate hydrogel. Appropriate cell dispensing conditions and optimum alginate concentrations for maintaining cell viability were determined. In vitro cell-based biochemical assays were performed to determine glycosaminoglycans (GAGs), DNA and total collagen contents from different PCL-alginate gel constructs. PCL-alginate gels containing transforming growth factor-β (TGFβ) showed higher ECM formation. The 3D cell-printed scaffolds of PCL-alginate gel were implanted in the dorsal subcutaneous spaces of female nude mice. Histochemical Alcian blue and haematoxylin and eosin (H&E) staining and immunohistochemical (type II collagen) analyses of the retrieved implants after 4 weeks revealed enhanced cartilage tissue and type II collagen fibril formation in the PCL-alginate gel (+TGFβ) hybrid scaffold. In conclusion, we present an innovative cell-printed scaffold for cartilage regeneration fabricated by an advanced bioprinting technology.
Patients with mitral stenosis and atrial fibrillation (AF) require anticoagulation for stroke prevention. Thus far, all studies on direct oral anticoagulants (DOACs) have excluded patients with ...moderate to severe mitral stenosis.
The aim of this study was to validate the efficacy of DOACs in patients with mitral stenosis.
The study population was enrolled from the Health Insurance Review and Assessment Service (HIRA) database in the Republic of Korea, and it included patients who were diagnosed with mitral stenosis and AF and either were prescribed DOACs for off-label use or received conventional treatment with warfarin. The primary efficacy endpoint was ischemic strokes or systemic embolisms, and the safety outcome was intracranial hemorrhage.
A total of 2,230 patients (mean age 69.7 ± 10.5 years; 682 30.6% males) were included in the present study. Thromboembolic events occurred at a rate of 2.22%/year in the DOAC group, and 4.19%/year in the warfarin group (adjusted hazard ratio for DOAC: 0.28; 95% confidence interval: 0.18 to 0.45). Intracranial hemorrhage occurred in 0.49% of the DOAC group and 0.93% of the warfarin group (adjusted hazard ratio for DOAC: 0.53; 95% confidence interval: 0.22 to 1.26).
In patients with AF accompanied with mitral stenosis, DOAC use is promising and hypothesis generating in preventing thromboembolism. Our results need to be replicated in a randomized trial.
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Epidermal growth factor receptor (EGFR) is frequently overexpressed in triple-negative breast cancer and is emerging as a therapeutic target. EGFR gene copy number alteration and mutation are highly ...variable and scientists have been challenged to define their prognostic significance in triple-negative breast cancer. We examined EGFR protein expression, EGFR gene copy number alteration and mutation of exon 18 to 21 in 151 cases of triple-negative breast cancer and correlated these findings with clinical outcomes. In addition, intratumoral agreement of EGFR protein overexpression and gene copy number alteration was evaluated. EGFR overexpression was found in 97 of 151 cases (64%) and high EGFR gene copy number was detected in 50 cases (33%), including 3 gene amplification (2%) and 47 high polysomy (31%). Five EGFR mutations were detected in 4 of 151 cases (3%) and included G719A in exon 18 (n=1), V786M in exon 20 (n=1), and L858R in exon 21 (n=3). One case had two mutations (G719A and L858R). High EGFR copy number, but not EGFR mutation, correlated with EGFR protein overexpression. Intratumoral heterogeneity of EGFR protein overexpression and EGFR copy number alteration was not significant. In survival analyses, high EGFR copy number was found to be an independent prognostic factor for poor disease-free survival in patients with triple-negative breast cancer. Our findings showed that EGFR mutation was a rare event, but high EGFR copy number was relatively frequent and correlated with EGFR overexpression in triple-negative breast cancer. Moreover, high EGFR copy number was associated with poor clinical outcome in triple-negative breast cancer, suggesting that evaluation of EGFR copy number may be useful for predicting outcomes in patients with triple-negative breast cancer and for selecting patients for anti-EGFR-targeted therapy.
The intratumoral heterogeneity (ITH) and the evolution of genomic architectures associated with the development of distant metastases are not well understood in colorectal cancers.
We performed ...multiregion biopsies of primary and liver metastatic regions from five colorectal cancers with whole-exome sequencing and copy number profiling.
In addition to a substantial level of genetic ITH, multiregion genetic profiling identifies the subclonal mutational architecture, leading to the region-based or spatial categorization of somatic mutations and the inference of intratumoral evolutionary history of cancers. The universal mutations (those observed in all the regional biopsies) are enriched in known cancer genes such as APC and TP53 with distinct mutational spectra compared with biopsy- or region-specific mutations, suggesting that major operative mutational mechanisms and their selective pressures are not constant across the metastatic progression. The phylogenies inferred from genomic data show branching evolutionary patterns where some primary biopsies are often segregated with metastastic lesions. Our analyses also revealed that copy number changes such as the chromosomal gains of c-MYC and chromothripsis can be region specific and the potential source of genetic ITH.
Our data show that the genetic ITH is prevalent in colorectal cancer serving as a potential driving force to generate metastasis-initiating clones and also as a means to infer the intratumoral evolutionary history of cancers. The paucity of recurrent metastasis-clonal events suggests that colorectal cancer distant metastases may not follow a uniform course of genomic evolution, which should be considered in the genetic diagnosis and the selection of therapeutic targets for the advanced colorectal cancer.
Reconfigurable intelligent surfaces (RIS) are expected to bring about a revolutionary transformation in vehicular networks, thus paving the way for a future characterized by connected and automated ...vehicles (CAV). An RIS is a planar structure comprising many passive elements that can dynamically manipulate electromagnetic waves to enhance wireless communication by reflecting, refracting, and focusing signals in a programmable manner. RIS exhibits substantial potential for improving vehicle-to-everything (V2X) communication through various means, including coverage enhancement, interference mitigation, improving signal strength, and providing additional layers of privacy and security. This article presents a comprehensive survey that explores the emerging opportunities arising from the integration of RIS into vehicular networks. To examine the convergence of RIS and V2X communications, the survey adopted a holistic approach, thus highlighting the potential benefits and challenges of this combination. In this study, we examined several applications of RIS-aided V2X communication. Subsequently, we delve into the fundamental emerging technologies that are expected to empower vehicular networks, encompassing mobile edge computing (MEC), non-orthogonal multiple access (NOMA), millimeter-wave communication (mmWave), Artificial Intelligence (AI), and visible light communication (VLC). Finally, to stimulate further research in this domain, we emphasize noteworthy research challenges and potential avenues for future exploration.
In this paper, a cosmological model with an isotropic form of the Morris–Thorne type wormhole was derived in a similar way to the McVittie solution to the black hole in the expanding universe. By ...solving Einstein's field equation with plausible matter distribution, we found the exact solution of the wormhole embedded in Friedmann–Lemaître–Robertson–Walker universe. We also found the apparent cosmological horizons from the redefined metric and analyzed the geometric natures, including causal and dynamic structures. The Hawking temperature for thermal radiation was obtained by the WKB approximation using the Hamilton–Jacobi equation and Hamilton's equation, near the apparent cosmological horizon.
Introduction
Novel ablation catheters equipped with mini‐electrodes (ME) offer high resolution mapping for target tissue. This study aimed to evaluate the mapping performance and efficacy of ME ...catheters in radiofrequency ablation (RFA) of paroxysmal supraventricular tachycardias (PSVTs).
Methods
We prospectively enrolled 136 patients undergoing RFA of PSVT including 76 patients with atrioventricular nodal reentrant tachycardia (AVNRT) and 60 patients with atrioventricular reentrant tachycardia (AVRT) or Wolff−Parkinson−White (WPW) syndrome. Patients were randomized to the ME group (ablation using ME catheters) or the control group (ablation using conventional catheters). The number of ablation attempt and cumulative ablation time to ablation endpoints, which was defined as an emergence of junctional rhythm in AVNRT or accessory pathway (AP) block in AVRT/WPW syndromes were compared.
Results
During ablation procedures, discrete slow pathway or AP electrograms were found in 27 (39.7%) patients in the ME group and 13 (19.1%) patients in the control group. The primary study outcomes were significantly lower in the ME group (ablation attempt number: 2.0 1–4 vs. 3.0 2–7 in the ME and control group, p = .032; ablation time: 23.5 5.0–111.5 vs. 64.5 16.0–185.0 s, p = .013). According to the PSVT diagnosis, ablation time to junctional rhythm was significantly shorter in the ME group in AVNRT. In AVRT/WPW syndrome, both ablation attempt number and ablation time to AP block were nonsignificantly lower in the ME group.
Conclusion
The novel ME catheter was advantageous for identifying pathway potentials and reducing initial ablation attempt number and ablation time to reach acute ablation endpoint for PSVTs (ClinicalTrials.gov number, NCT04215640).
The design and implementation of a high-efficiency nonisolated single-stage on-board battery charger (OBC) for electric vehicles are presented. Reviewing the conventional topologies, a suitable ...circuit structure is determined to charge a battery in a wide spectrum of input and output conditions. Additionally, a suitable strategy for a highly efficient OBC is presented through the analysis of selected topology. A detailed theoretical analysis, operating strategy, and experimental results on a 3.7-kW prototype are presented in order to evaluate the performance of the proposed system.
This paper proposes a novel integrated low-voltage dc-dc converter (LDC) and onboard battery charger (OBC) for electric vehicles (xEVs) that share heatsinks, terminals, sensing circuits, and circuit ...components between both parts. The proposed OBC-LDC integrated power unit (OLPU) can be simplified by modifying the internal connections of the vehicle, thus eliminating the cost of high-power cables. In addition, the OLPU decreases the number of circuit components and increases the total power density by combining or sharing heatsinks, terminals, sensing circuits, and circuit components. Further, the proposed circuit satisfies the performance characteristics of conventional OBCs and LDCs and can be operated as such. Moreover, a simultaneous charging method for both a high-voltage battery and a low-voltage battery is suggested through an additional operational mode that results from the integration. This paper also specifically describes the operating characteristics and the design method in each mode. Design considerations, including possible problems with the integrated circuit structure, are presented, and an additional compensation circuit is suggested to solve these problems. The prototype is built, and experiments are carried out to verify the performance and validity of the proposed power unit.
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