A droplet-based electricity generator with high instantaneous power density.

Extensive efforts have been made to harvest energy from water in the form of raindrops1-6, river and ocean waves7,8, tides9 and others10-17. However, achieving a high density of electrical power generation is challenging. Traditional hydraulic power generation mainly uses electromagnetic generators that are heavy, bulky, and become inefficient with low water supply. An alternative, the water-droplet/solid-based triboelectric nanogenerator, has so far generated peak power densities of less than one watt per square metre, owing to the limitations imposed by interfacial effects-as seen in characterizations of the charge generation and transfer that occur at solid-liquid1-4 or liquid-liquid5,18 interfaces. Here we develop a device to harvest energy from impinging water droplets by using an architecture that comprises a polytetrafluoroethylene film on an indium tin oxide substrate plus an aluminium electrode. We show that spreading of an impinged water droplet on the device bridges the originally disconnected components into a closed-loop electrical system, transforming the conventional interfacial effect into a bulk effect, and so enhancing the instantaneous power density by several orders of magnitude over equivalent devices that are limited by interfacial effects.

Converting a probe-based fluorescence system into an easy-to-use adjunct for the detection of parathyroid glands accidentally resected intraoperatively.

PURPOSE: The reported threshold of a near-infrared fluorescence detection probe (FDP) for judging parathyroid glands (PGs) is based on the autofluorescence intensity relative to other non-PG tissues, making it unreliable when not enough reference tissues are measured. We aim to convert FDP into a more convenient tool for identifying accidentally resected PGs by quantitative measurements of autofluorescence in resected tissues. METHODS: It was a prospective study approved by the Institutional Review Board. The research was divided into two stages: (1) In order to calibrate the novel FDP system, autofluorescence intensity of different in / ex vivo tissues was measured and the optimal threshold was obtained using receiver operating characteristic (ROC) curve. (2) To further validate the effectiveness of the new system, detection rates of incidental resected PGs by pathology in the control group and by FDP in the experimental group were compared. RESULTS: Autofluorescence of PGs was significantly higher than that of non-PG tissue (43 patients, Mann-Whitney U test, p < 0.0001). An optimal threshold of sensitivity / specificity (78.8% and 85.1%) for discriminating PGs was obtained. The detection rates of experimental group (20 patients) and control group (33 patients) are 5.0% and 6.1% respectively (one-tailed Fisher's exact test, p = 0.6837), indicating the novel FDP system can achieve a similar proportion of PG detection compared with pathological examinations. CONCLUSIONS: The novel FDP system can be used as an easy-to-use adjunct for detecting PG accidentally resected intraoperatively before the tissues are sent for frozen sections during thyroidectomy surgeries. TRIAL REGISTRATION: Registration number: ChiCTR2200057957.

Autofluorescence detection and co-axial projection for intraoperative localization of parathyroid gland.

BACKGROUND: Near-infrared (NIR) autofluorescence detection is an effective method for identifying parathyroid glands (PGs) in thyroidectomy or parathyroidectomy. Fiber optical probes provide quantitative autofluorescence measurements for PG detection owing to its high sensitivity and high excitation light cut-off efficiency at a fixed detection distance. However, an optical fiber probe lacks the imaging capability and cannot map the autofluorescence distribution on top of normal tissue background. Therefore, there is a need for intraoperative mapping of PGs with high sensitivity and imaging resolution. METHODS: We have developed a fluorescence scanning and projection (FSP) system that combines a scanning probe and a co-axial projector for intraoperative localization and in situ display of PGs. Some of the key performance characteristics, including spatial resolution and sensitivity for detection, spatial resolution for imaging, dynamic time latency, and PG localization capability, are characterized and verified by benchtop experiments. Clinical utility of the system is simulated by a fluorescence-guided PG localization surgery on a tissue-simulating phantom and validated in an ex vivo experiment. RESULTS: The system is able to detect indocyanine green (ICG) solution of 5 pM at a high signal-to-noise ratio (SNR). Additionally, it has a maximal projection error of 0.92 mm, an averaged projection error of 0.5 ± 0.23 mm, and an imaging resolution of 748 µm at a working distance ranging from 35 to 55 cm. The dynamic testing yields a short latency of 153 ± 54 ms, allowing for intraoperative scanning on target tissue during a surgical intervention. The simulated fluorescence-guided PG localization surgery has validated the system's capability to locate PG phantom with operating room ambient light interference. The simulation experiment on the PG phantom yields a position detection bias of 0.36 ± 0.17 mm, and an area intersection over unit (IoU) of 76.6% ± 6.4%. Fluorescence intensity attenuates exponentially with the thickness of covered tissue over the PG phantom, indicating the need to remove surrounding tissue in order to reveal the weak autofluorescence signal from PGs. The ex vivo experiment demonstrates the technical feasibility of the FSP system for intraoperative PG localization with accuracy. CONCLUSION: We have developed a novel probe-based imaging and navigation system with high sensitivity for fluorescence detection, capability for fluorescence image reconstruction, multimodal image fusion and in situ PG display function. Our studies have demonstrated its clinical potential for intraoperative localization and in situ display of PGs in thyroidectomy or parathyroidectomy.

Stimuli-responsive nanobubbles for biomedical applications.

Stimuli-responsive nanobubbles have received increased attention for their application in spatial and temporal resolution of diagnostic techniques and therapies, particularly in multiple imaging methods, and they thus have significant potential for applications in the field of biomedicine. This review presents an overview of the recent advances in the development of stimuli-responsive nanobubbles and their novel applications. Properties of both internal- and external-stimuli responsive nanobubbles are highlighted and discussed considering the potential features required for biomedical applications. Furthermore, the methods used for synthesis and characterization of nanobubbles are outlined. Finally, novel biomedical applications are proposed alongside the advantages and shortcomings inherent to stimuli-responsive nanobubbles.

Low-cost thermal imaging with machine learning for non-invasive diagnosis and therapeutic monitoring of pneumonia.

Rapid screening and early treatment of lung infection are essential for effective control of many epidemics such as Coronavirus Disease 2019 (COVID-19). Recent studies have demonstrated the potential correlation between lung infection and the change of back skin temperature distribution. Based on these findings, we propose to use low-cost, portable and rapid thermal imaging in combination with image-processing algorithms and machine learning analysis for non-invasive and safe detection of pneumonia. The proposed method was tested in 69 subjects (30 normal adults, 11 cases of fever without pneumonia, 19 cases of general pneumonia and 9 cases of COVID-19) where both RGB and thermal images were acquired from the back of each subject. The acquired images were processed automatically in order to extract multiple location and shape features that distinguish normal subjects from pneumonia patients at a high accuracy of 93 % . Furthermore, daily assessment of two pneumonia patients by the proposed method accurately predicted the clinical outcomes, coincident with those of laboratory tests. Our pilot study demonstrated the technical feasibility of portable and intelligent thermal imaging for screening and therapeutic assessment of pneumonia. The method can be potentially implemented in under-resourced regions for more effective control of respiratory epidemics.

Oblique interface shearing (OIS): single-step microdroplet generation and on-demand positioning.

A new process for simultaneous generation and positioning of microdroplets within a single step named oblique interface shearing (OIS) is reported based on the observation that liquid microdroplets generated by vibrating a thin capillary across the air-liquid interface at an oblique angle exhibit notable lateral displacements. An analytical model is established to describe the lateral droplet displacement induced by the Stokes drift effect. The dependency of the lateral displacement on typical operating parameters allows for on-demand droplet positioning while they are produced. The efficacy of the process is validated through delivering microdroplets with the same size to different positions as well as size-dependent positioning of these microdroplets.

Fundus-simulating phantom for calibration of retinal vessel oximetry devices.

Retinal vessel oxygen supply is important for retinal tissue metabolism. Commonly used retinal vessel oximetry devices are based on dual-wavelength spectral measurement of oxyhemoglobin and deoxyhemoglobin. However, there is no traceable standard for reliable calibration of these devices. In this study, we developed a fundus-simulating phantom that closely mimicked the optical properties of human fundus tissues. Microchannels of precisely controlled topological structures were produced by soft lithography to simulate the retinal vasculature. Optical properties of the phantom were adjusted by adding scattering and absorption agents to simulate different concentrations of fundus pigments. The developed phantom was used to calibrate the linear correlation between oxygen saturation (SO2) level and optical density ratio in a dual-wavelength oximetry device. The obtained calibration factors were used to calculate the retinal vessel SO2 in both eyes of five volunteers aged between 24 and 27 years old. The test results showed that the mean arterial and venous SO2 levels after phantom calibration were coincident with those after empirical value calibration, indicating the potential clinical utility of the produced phantom as a calibration standard.

"Magnus nano-bullets" as T1/T2 based dual-modal for in vitro and in vivo MRI visualization.

Tissue specific T1/T2 dual contrast abilities for magnetic resonance imaging (MRI) have great significance in initial detection of cancer lesions. Herein, we developed a novel kind of Magnus nano-bullets (Mn-DTPA-F-MSNs) distinguished by magnetic (Fe3O4-NPs) head combined with mesoporous (SiO2) persist body, respectively. Subsequently, modify mesoporous SiO2 group and finally loaded with Mn2+. These Magnus nano-bullets have relaxivity value (r1 = 5.12 mM-1 s-1) and relaxivity value (r2 = 265.32 mM-1 s-1); they were > 2 folds in comparison to control at 3.0 T. Meanwhile, Magnus nano-bullets also offered significant enhancements for the detection of Glutathione (GSH), a biomarker that has been showed a redox responsive T1-weighted MRI effect in vitro and in vivo evaluations with good biocompatibility. Therefore, our finding endorses that Magnus nano-bullets offer a "smart" and tremendous strategy for greater GSH responsive T1/T2 dual MRI image probes for future biomedical applications.

One-step microencapsulation and spraying of pesticide formulations for improved adhesion and sustained release.

Aim: To reduce the contamination arising from abuse of commercial pesticide formulations, the coaxial electrospray (CES) method was used for one-step microencapsulation and spraying of pesticides. Methods: After optimisation of process parameters, polymeric microcapsules with different structures were fabricated as the carriers of azoxystrobin (AZS). For the resultant microcapsules, the sustained pesticide release was verified in vitro and the adhesion properties were investigated through a normalised rinsing test. Results: The maximum encapsulation efficiency of the fabricated AZS-loaded microcapsules was 99.14%. Compared to commercial AZS aqueous suspension, the microcapsules fabricated by the CES method exhibited improved sustained release performance of AZS, which could be readily controlled by adjusting the shell thicknesses. Moreover, highly enhanced adhesion performance was observed for the AZS-loaded microcapsules directly sprayed in CES process. Conclusions: The CES process is promising to be applied as a one-step microencapsulation and spraying technology for improving pesticide utilisation and reducing environmental pollution.

Design of a portable phantom device to simulate tissue oxygenation and blood perfusion.

We propose a portable phantom system for calibration and validation of medical optical devices in a clinical setting. The phantom system comprises a perfusion module and an exchangeable tissue-simulating phantom that simulates tissue oxygenation and blood perfusion. The perfusion module consists of a peristaltic pump, two liquid storage units, and two pressure suppressors. The tissue-simulating phantom is fabricated by a three-dimensional (3D) printing process with microchannels embedded to simulate blood vessels. Optical scattering and absorption properties of biologic tissue are simulated by mixing graphite powder and titanium dioxide powder with clear photoreactive resin at specific ratios. Tissue oxygen saturation (StO2) and blood perfusion are simulated by circulating the mixture of blood and intralipid at different oxygenation levels and flow rates. A house-made multimodal imaging system that combines multispectral imaging and laser speckle imaging are used for non-invasive detection of phantom oxygenation and perfusion, and the measurements are compared with those of a commercial Moor device as well as numerical simulation. By acquiring multimodal imaging data from one phantom and applying the calibration factors in different settings, we demonstrate the technical feasibility to calibrate optical devices for consistent measurements. By simulating retina tissue vasculature and acquiring functional images at different tissue oxygenation and blood perfusion levels, we demonstrate the clinical potential to simulate tissue anomalies. Our experiments imply the clinical potential of a portable, low-cost, and traceable phantom standard to calibrate and validate medical optical devices for improved performance.

Fabrication of a multilayer tissue-mimicking phantom with tunable optical properties to simulate vascular oxygenation and perfusion for optical imaging technology.

Vast research has been carried out to fabricate tissue-mimicking phantoms, due to their convenient use and ease of storage, to assess and validate the performance of optical imaging devices. However, to the best of our knowledge, there has been little research on the use of multilayer tissue phantoms for optical imaging technology, although their structure is closer to that of real skin tissue. In this work, we design, fabricate, and characterize multilayer tissue-mimicking phantoms, with a morphological mouse ear blood vessel, that contain an epidermis, a dermis, and a hypodermis. Each tissue-mimicking phantom layer is characterized individually to match specific skin tissue layer characteristics. The thickness, optical properties (absorption coefficient and reduced scattering coefficient), oxygenation, and perfusion of skin are the most critical parameters for disease diagnosis and for some medical equipment. These phantoms can be used as calibration artifacts and help to evaluate optical imaging technologies.

Reduction-Triggered Transformation of Disulfide-Containing Micelles at Chemically Tunable Rates.

A dilemma exists between the circulation stability and cargo release/mass diffusion at desired sites when designing delivery nanocarriers and in vivo nanoreactors. Reported herein are disulfide-crosslinked (DCL) micelles exhibiting reduction-triggered switching of crosslinking modules and synchronized hydrophobic-to-hydrophilic transition. Tumor cell targeted DCL micelles undergo cytoplasmic milieu triggered disulfide cleavage and self-immolative decaging reactions at chemically adjustable rates, generating primary amine moieties. Extensive amidation reactions with neighboring ester moieties then occur because of the high local concentration and suppression of the apparent amine pKa  value within the hydrophobic cores, thus leading to the transformation of crosslinking modules and formation of tracelessly crosslinked (TCL) micelles, with hydrophilic cores, inside live cells. We further integrate this design principle with theranostic nanocarriers for selective intracellular drug transport guided by enhanced magnetic resonance (MR) imaging performance.

Simultaneous Measurements of Geometric and Viscoelastic Properties of Hydrogel Microbeads Using Continuous-Flow Microfluidics with Embedded Electrodes.

Geometric and mechanical characterizations of hydrogel materials at the microscale are attracting increasing attention due to their importance in tissue engineering, regenerative medicine, and drug delivery applications. Contemporary approaches for measuring the these properties of hydrogel microbeads suffer from low-throughput, complex system configuration, and measurement inaccuracy. In this work, a continuous-flow device is developed to measure geometric and viscoelastic properties of hydrogel microbeads by flowing the microbeads through a tapered microchannel with an array of interdigitated microelectrodes patterned underneath the channel. The viscoelastic properties are derived from the trajectories of microbeads using a quasi-linear viscoelastic model. The measurement is independent of the applied volumetric flow rate. The results show that the geometric and viscoelastic properties of Ca-alginate hydrogel microbeads can be determined independently and simultaneously. The bulky high-speed optical systems are eliminated, simplifying the system configuration and making it a truly miniaturized device. A throughput of up to 394 microbeads min-1 is achieved. This study may provide a powerful tool for mechanical profiling of hydrogel microbeads to support their wide applications.

Characteristics of Artemether-Loaded Poly(lactic-co-glycolic) Acid Microparticles Fabricated by Coaxial Electrospray: Validation of Enhanced Encapsulation Efficiency and Bioavailability.

Artemether is one of the most effective drugs for the treatment of chloroquine-resistant and Plasmodium falciparum strains of malaria. However, its therapeutic potency is hindered by its poor bioavailability. To overcome this limitation, we have encapsulated artemether in poly(lactic-co-glycolic) acid (PLGA) core-shell microparticles (MPs) using the coaxial electrospray method. With optimized process parameters including liquid flow rates and applied electric voltages, experiments are systematically carried out to generate a stable cone-jet mode to produce artemether-loaded PLGA-MPs with an average size of 2 µm, an encapsulation efficiency of 78 ± 5.6%, and a loading efficiency of 11.7%. The in vitro release study demonstrates the sustained release of artemether from the core-shell structure in comparison with that of plain artemether and that of MPs produced by single-axial electrospray without any relevant cytotoxicity. The in vivo studies are performed to evaluate the pharmacokinetic characteristics of the artemether-loaded PLGA-MPs. Our study implies that artemether can be effectively encapsulated in a protective shell of PLGA for controlled release kinetics and enhanced oral bioavailability.

Multi-scale hyperspectral imaging of cervical neoplasia.

PURPOSE: This preliminary study aimed at investigating the feasibility and effective of multi-scale hyperspectral imaging in detecting cervical neoplasia at both tissue and cellular levels. METHODS: In this paper, we describe a noninvasive diagnosis method with a hyperspectral imager for detection and location of cervical intraepithelial neoplasia (CIN) at multiple scales. At the macroscopic level, the hyperspectral imager was applied to capture the reflectance images of the entire cervix in vivo at a series of wavelengths. At the microscopic level, the hyperspectral imager was coupled with a microscope to collect the transmittance images of the pathological slide. The collected image data were calibrated. A wide-gap second derivative analysis was applied to differentiate CIN from other types of tissue. RESULTS: At both macroscopic and microscopic levels, hyperspectral imaging analysis results were consistent with those of histopathological analysis, indicating the technical feasibility of multi-scale hyperspectral imaging for cervical neoplasia detection with accuracy and efficacy. CONCLUSION: We propose a multi-scale hyperspectral imaging method for noninvasive detection of cervical neoplasia. Comparison of the imaging results with those of gold standard histologic measurements demonstrates that the hyperspectral diagnostic imaging system can distinguish CIN at both tissue and cellular levels.

Targeted Microbubbles for Ultrasound Mediated Short Hairpin RNA Plasmid Transfection to Inhibit Survivin Gene Expression and Induce Apoptosis of Ovarian Cancer A2780/DDP Cells.

Nonviral gene transfer by ultrasound-targeted microbubble destruction (UTMD) is an promising technique for RNA interference (RNAi) therapy. Targeting silence survivin gene may provide an important therapeutic option for patients with ovarian cancer. However, UTMD mediated RNAi therapy typically uses nontargeted microbubbles with suboptimal gene transfection efficiency. In this work, a LHRHa targeted microbubble agent and recombinant expression plasmid of shRNA targeting survivin gene (pshRNA survivin) were constructed for UTMD mediated pshRNA survivin therapy in ovarian cancer A2780/DDP cells that express LHRH receptors. The targeted microbubbles (TMBs) mixed with the pshRNA survivin were added to cultured ovarian cancer cells followed by ultrasound exposure (1 MHz, 0.5 W/cm(2)) for 30 s. After transfection for 48 h, the expression of survivin mRNA and protein were (0.36 ± 0.036) and (0.05 ± 0.02), respectively. The cell proliferation inhibitory rates at 24, 48, and 72 h after treatment are (42.08 ± 3.20)%, (54.60 ± 1.02)%, and (74.25 ± 2.14)%, respectively, and the apoptosis rate was (28.99 ± 2.70)%. The expression of apoptosis related protein caspase-9 and caspase-3 were (0.95 ± 0.09) and (2.6 ± 0.21). In comparison with the other treatment groups, ultrasound mediation of targeted microbubbles yielded higher RNAi efficiency and higher cell apoptosis rate and cell proliferation inhibitory rate (p < 0.05). Our experiment verifies the hypothesis that ultrasound mediation of targeted microbubbles will enhance RNAi efficiency in ovarian cancer cells. This novel method for RNA interference represents a powerful, promising no viral technology that can be used in the tumor gene therapy and research.

Ultrasound-mediated destruction of LHRHa-targeted and paclitaxel-loaded lipid microbubbles for the treatment of intraperitoneal ovarian cancer xenografts.

Ultrasound-targeted microbubble destruction (UTMD) is a promising technique to facilitate the delivery of chemotherapy in cancer treatment. However, the process typically uses nonspecific microbubbles, leading to low tumor-to-normal tissue uptake ratio and adverse side effects. In this study, we synthesized the LHRH receptor-targeted and paclitaxel (PTX)-loaded lipid microbubbles (TPLMBs) for tumor-specific binding and enhanced therapeutic effect at the tumor site. An ovarian cancer xenograft model was established by injecting A2780/DDP cells intraperitoneally in BALB/c nude mice. Microscopic imaging of tumor sections after intraperitoneal injection of TPLMBs showed effective binding of the microbubbles with cancer cells. Ultrasound mediated destruction of the intraperitoneally injected TPLMBs yielded a superior therapeutic outcome in comparison with other treatment options. Immunohistochemical analyses of the dissected tumor tissue further confirmed the increased tumor apoptosis and reduced angiogenesis. Our experiment suggests that ultrasound-mediated intraperitoneal administration of the targeted drug-loaded microbubbles may be a useful method for the treatment of ovarian cancer.

Ultrasound-mediated destruction of LHRHa-targeted and paclitaxel-loaded lipid microbubbles induces proliferation inhibition and apoptosis in ovarian cancer cells.

Although paclitaxel (PTX) is used with platinum as the first line chemotherapy regimen for ovarian cancer, its clinical efficacy is often limited by severe adverse effects. Ultrasound-targeted microbubble destruction (UTMD) technique holds a great promise in minimizing the side effects and maximizing the therapeutic efficacy. However, the technique typically uses nontargeted microbubbles with suboptimal efficiency. We synthesized targeted and PTX-loaded microbubbles (MBs) for UTMD mediated chemotherapy in ovarian cancer cells. PTX-loaded lipid MBs were coated with a luteinizing hormone-releasing hormone analogue (LHRHa) through a biotin-avidin linkage to target the ovarian cancer A2780/DDP cells that express the LHRH receptor. In the cell culture studies, PTX-loaded and LHRHa-targeted MBs (TPLMBs) in combination with ultrasound (300 kHz, 0.5 W/cm(2), 30 s) demonstrated antiproliferative activities of 41.30 ± 3.93%, 67.76 ± 2.45%, and 75.93 ± 2.81% at 24, 48, and 72 h after the treatment, respectively. The cell apoptosis ratio at 24 h after the treatment is 32.6 ± 0.79%, which is significantly higher than other treatment groups such as PTX only and no-targeted PTX-loaded MBs (NPLMBs) with or without ultrasound mediation. Our experiment verifies the hypothesis that ultrasound mediation of ovarian cancer-targeted and drug-loaded MBs will enhance the PTX therapeutic efficiency.

Free-Boundary Microfluidic Platform for Advanced Materials Manufacturing and Applications.

Microfluidics, with its remarkable capacity to manipulate fluids and droplets at the microscale, has emerged as a powerful platform in numerous fields. In contrast to conventional closed microchannel microfluidic systems, free-boundary microfluidic manufacturing (FBMM) processes continuous precursor fluids into jets or droplets in a relatively spacious environment. FBMM is highly regarded for its superior flexibility, stability, economy, usability, and versatility in the manufacturing of advanced materials and architectures. In this review, a comprehensive overview of recent advancements in FBMM is provided, encompassing technical principles, advanced material manufacturing, and their applications. FBMM is categorized based on the foundational mechanisms, primarily comprising hydrodynamics, interface effects, acoustics, and electrohydrodynamic. The processes and mechanisms of fluid manipulation are thoroughly discussed. Additionally, the manufacturing of advanced materials in various dimensions ranging from zero-dimensional to three-dimensional, as well as their diverse applications in material science, biomedical engineering, and engineering are presented. Finally, current progress is summarized and future challenges are prospected. Overall, this review highlights the significant potential of FBMM as a powerful tool for advanced materials manufacturing and its wide-ranging applications.

SCAC: A Semi-Supervised Learning Approach for Cervical Abnormal Cell Detection.

Cervical abnormal cell detection plays a crucial role in the early screening of cervical cancer. In recent years, some deep learning-based methods have been proposed. However, these methods rely heavily on large amounts of annotated images, which are time-consuming and labor-intensive to acquire, thus limiting the detection performance. In this paper, we present a novel Semi-supervised Cervical Abnormal Cell detector (SCAC), which effectively utilizes the abundant unlabeled data. We utilize Transformer as the backbone of SCAC to capture long-range dependencies to mimic the diagnostic process of pathologists. In addition, in SCAC, we design a Unified Strong and Weak Augment strategy (USWA) that unifies two data augmentation pipelines, implementing consistent regularization in semi-supervised learning and enhancing the diversity of the training data. We also develop a Global Attention Feature Pyramid Network (GAFPN), which utilizes the attention mechanism to better extract multi-scale features from cervical cytology images. Notably, we have created an unlabeled cervical cytology image dataset, which can be leveraged by semi-supervised learning to enhance detection accuracy. To the best of our knowledge, this is the first publicly available large unlabeled cervical cytology image dataset. By combining this dataset with two publicly available annotated datasets, we demonstrate that SCAC outperforms other existing methods, achieving state-of-the-art performance. Additionally, comprehensive ablation studies are conducted to validate the effectiveness of USWA and GAFPN. These promising results highlight the capability of SCAC to achieve high diagnostic accuracy and extensive clinical applications.