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Multivariate Model of the Intersubject Variability of the Retinal Nerve Fiber Layer Thickness in Healthy Subjects
摘要： We present and validate a multivariate model that partially compensates for retinal nerve fiber layer (RNFL) intersubject variability. A total of 202 healthy volunteers randomly attributed to a training (TS) and a validation (VS) sample underwent complete ophthalmic examination, including Fourier-domain optical coherence tomography (FD-OCT). We acquired FD-OCT data centered at the optic disc (OD) and the macula. Two-dimensional (2D) projection images were computed and registered, to determine the distance between fovea and OD centers (FD) and their respective angle (FA). Retinal vessels were automatically segmented in the projection images and used to calculate the circumpapillary retinal vessel density (RVD) profile. Using the TS, a multivariate model was calculated for each of 256 sectors of the RNFL, including OD ratio, orientation and area, RVD, FD, FA, age, and refractive error. Model selection was based on Akaike Information Criteria. The compensation effect was determined for 12 clock hour sectors, comparing the coefficients of variation (CoV) of measured and model-compensated RNFL thicknesses. The model then was applied to the VS, and CoV was calculated. The R value for the multivariate model was, on average 0.57 (max = 0.68). Compensation reduced the CoV on average by 18%, both for the TS and VS (up to 23% and 29%), respectively. We have developed and validated a comprehensive multivariate model that may be used to create a narrower range of normative RNFL data, which could improve diagnostic separation between early glaucoma and healthy subjects. This, however, remains to be demonstrated in future studies.
关键词： physiological biomarkers,multivariate model,retinal nerve fiber layer
更新于2025-09-23 15:21:01
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Matrix-assisted laser desorption ionization-time of flight mass spectrometry-based method for accurate discrimination of Staphylococcus schleiferi subspecies
摘要： S. schleiferi is one of the main species isolated from canine otitis externa, pyoderma and from apparently healthy dogs. The species is divided into two subspecies, S. schleiferi schleiferi and S. schleiferi coagulans. MALDI-TOF MS does not distinguish correctly these two subspecies. This study aimed to identify biomarkers that could possibly discriminate Staphylococcus schleiferi subspecies by MALDI-TOF MS. Twelve strains (eight S. schleiferi schleiferi and four S. schleiferi coagulans) were firstly identified. Each isolate was submitted to a protein extraction protocol and used for improved subspecies identification in clinical samples.
关键词： MALDI-TOF MS,Staphylococcus schleiferi,biomarkers
更新于2025-09-23 15:19:57
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Diode Laser Spectroscopy for Creating Effective Measuring Systems and Their Use in Biological and Medical Research
摘要： In this paper, we present the most important principles of diode laser spectroscopy, which allow one to create fundamentally new measuring systems for diverse applications in biology and medicine. Using the diode laser spectroscopy method and its primary hardware implementation the emission of gas molecules from skin of the hand was registered and ammonia skin emission was found to be dominant. The properties of exhaled air from patients in different states were determined with another special measuring complex of diode laser spectroscopy. It was shown that when the functional state of the body changes, the gas composition of molecular substances that are present in the exhaled air is altered indirectly and their levels vary significantly depending on the health of the individual. Our findings suggest that it is possible to study the specific functional properties of the human body to facilitate assessment of the health of an individual to determine whether pathological processes occur in the body at various stages of their severity using diode laser spectroscopy. This paper presents clinical and experimental data on this issue.
关键词： non-invasive diagnostics,diode lasers,gas biomarkers,diode laser spectroscopy
更新于2025-09-23 15:19:57
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Sensitive and Rapid Cancer Diagnosis with Immunoplasmonic Assay Based on Plasmonic Nanoparticles: Toward Fine-Needle Aspiration Cytology
摘要： Fine-needle aspiration cytology is a minimally invasive diagnostic strategy. However, collected specimens have to undergo a series of complex preparation steps, thus limiting the use of fine-needle aspiration cytology as a diagnostic approach for cytopathologists. In this study, we propose a cytology approach, easily adaptable to conventional one, by employing plasmonic biomarkers (gold(red_scattering), silver/gold(blue_scattering), and silver/gold(green_scattering) nanoparticles), each having a well-defined optical feature. Plasmonic nanoparticles, incubated with the suspension cells, are fully visible and differentiable on the cell membranes under the darkfield lateral RGB (Red-Green-Blue) side-illumination microscopy. The post-fabrication of plasmonic nanoparticles by the conjugation of a specific antibody (anti-human epidermal growth factor receptor 2: HER2) directly allows to visualize the selectively recognized antigens of the suspension cells (MDA-MB-453++HER2 and Jurkat-HER2) in co-cultures and individual cultures by using the side-illumination compared to the conventional dark-field visualization protocol. We also incubate two cancer cell lines (trypsinized MDA-MB-231++CD44 and MDA-MB-453++HER2) with anti-CD44 and anti-HER2 functionalized plasmonic nanoparticles, and nano-immunoplasmonic and immunofluorescence assays show a good agreement with each other for the recognition of expressed antigens (CD44 and HER2). Our results demonstrate a remarkable potential of plasmonic nanoparticles for a simple and rapid examination of small population of cells from collected specimens by using nano-immunoplasmonic approach and the side-illumination microscopy.
关键词： Fine-needle aspiration cytology,Plasmonic nanoparticles,Plasmonic biomarkers,Cancer diagnosis,Immunoplasmonic Assay,Side-illumination microscopy
更新于2025-09-23 15:19:57
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[IEEE 2019 IEEE SENSORS - Montreal, QC, Canada (2019.10.27-2019.10.30)] 2019 IEEE SENSORS - Fast response hydrogel-based plasmonic sensor substrate for the detection of ethanol
摘要： Decades of heavy investment in laboratory-based brain imaging and neuroscience have led to foundational insights into how humans sense, perceive, and interact with the external world. However, it is argued that fundamental differences between laboratory-based and naturalistic human behavior may exist. Thus, it remains unclear how well the current knowledge of human brain function translates into the highly dynamic real world. While some demonstrated successes in real-world neurotechnologies are observed, particularly in the area of brain-computer interaction technologies, innovations and developments to date are limited to a small science and technology community. We posit that advancements in real-world neuroimaging tools for use by a broad-based workforce will dramatically enhance neurotechnology applications that have the potential to radically alter human–system interactions across all aspects of everyday life. We discuss the efforts of a joint government-academic-industry team to take an integrative, interdisciplinary, and multi-aspect approach to translate current technologies into devices that are truly ?eldable across a range of environments. Results from initial work, described here, show promise for dramatic advances in the ?eld that will rapidly enhance our ability to assess brain activity in real-world scenarios.
关键词： brain computer interfaces,data acquisition,biomarkers,translational research,brain computer interaction,monitoring,wearable sensors,body sensor networks,electroencephalography,Behavioral science
更新于2025-09-23 15:19:57
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New tools for pathology: a user's review of a highly multiplexed method for <i>in situ</i> analysis of protein and RNA expression in tissue
摘要： Tumor cell heterogeneity and tumor cell - stromal interactions are being explored as determinants of disease progression and treatment resistance in solid tumor and hematologic malignancies. As such, tools simultaneously capable of highly-multiplexed profiling of tissues’ protein and RNA content, as well as interrogation of rare or single cells, are required to precisely characterize constituent tumor cell populations, infiltrating lymphocytes and stromal elements. Access to spatial relationships will enable more precise characterization of tumors, support patient stratification and may help to identify novel drug targets. Multiple platforms are being developed to address these critical unmet needs. The NanoString Digital Spatial Profiling (DSP) platform enables highly multiplexed, spatial assessment of protein and/or RNA targets in tissues by detecting oligonucleotide barcodes conjugated via a photocleavable linker to primary antibodies or nucleic acid probes. While this platform enables high-dimensional spatial interrogation of tissue protein and RNA expression, a detailed understanding of its composition, function and chemistry is advisable to guide experimental design and data interpretation. The purpose of this review is to provide an independent, comprehensive description of the DSP technology including an overview of NanoString’s capture and antibody barcode conjugation chemistries, experimental workflow, data output and analysis methods. The DSP technology will be discussed in the context of other highly multiplexed immunohistochemistry methods, including imaging mass cytometry (IMC) and multiplexed ion beam imaging (MIBI), to inform potential users of the advantages and limitations of each. Additional issues such as pre-analytical variability, sampling and specimen adequacy will be considered with respect to the platforms to inform potential experimental design.
关键词： tissue biomarkers,in situ hybridization,multiplexed immunohistochemistry,NanoString,tumor microenvironment
更新于2025-09-23 15:19:57
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A fully automated pipeline of extracting biomarkers to quantify vascular changes in retina-related diseases
摘要： This paper presents an automated system for extracting retinal vascular biomarkers for early detection of diabetes. The proposed retinal vessel enhancement, segmentation, optic disc (OD) and fovea detection algorithms provide fundamental tools for extracting the vascular network within the pre-defined region of interest. Based on that, the artery/vein classification, vessel width, tortuosity and fractal dimension measurement tools are used to assess a large number of quantitative vascular biomarkers. We evaluate our pipeline module by module against human annotations. The results indicate that our automated system is robust to the localisation of OD and fovea, segmentation of vessels and classification of arteries/veins. The proposed pipeline helps to increase the effectiveness of the biomarkers extraction and analysis for the early diabetes, and therefore, has the large potential of being further incorporated into a computer-aided diagnosis system.
关键词： diabetes,Retinal image analysis,vessel biomarkers,computer-aided diagnosis
更新于2025-09-19 17:15:36
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Recent advances in dual-emission ratiometric fluorescence probes for chemo/biosensing and bioimaging of biomarkers
摘要： A biomarker-based detection improves early diagnosis and subsequent treatment of diseases. Chemo/biosensing and bioimaging play a crucial role in biomarker detection. Ratiometric fluorescence (FL) probes provide built-in self-calibration for the correction of various target-independent factors and attract particular attention for analytical sensing and optical imaging. Based on the potential to provide a precise, quantitative, visual and real-time analysis, ratiometric FL probes are widely employed for chemo/biosensing and bioimaging detection of biomarkers. In this review, we systematically summarize the recent progress on dual-emission ratiometric FL probes. First, two general categories of ratiometric FL probes are introduced, involving ratiometric FL with one reference signal and two reversible signal changes. Then, fabrication methods of ratiometric FL probes are summarized in detail, including nanoparticle- or organic dye-embedded probes with dual-emission FL, fluorescent nanoparticles and organic dyes dual-embedded probes. Analytical applications of ratiometric FL probes are described overall, referring to different biomarker types and detection mechanisms, ratiometric FL chemo/biosensing in external samples and FL visual detection, ratiometric FL bioimaging in cells and tissues of small animals. Current states, probable challenges and future perspectives of ratiometric FL probes for biomarker detection are discussed rationally. This comprehensive review is attractive for numerous scientists from different areas, such as material science, chemistry, biomedicine, engineering, physics, etc. This review covers a wide range of scientific disciplines and benefits further development of functionalized optical materials, luminescent devices and bioimaging technique.
关键词： Biomarkers,Biosensors,Visual detection,Bioimaging,Ratiometric fluorescence
更新于2025-09-19 17:15:36
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Machine learning algorithms enhance the specificity of cancer biomarker detection using SERS-based immunoassays in microfluidic chips
摘要： Specificity is a challenge in liquid biopsy and early diagnosis of various diseases. There are only a few biomarkers that have been approved for use in cancer diagnostics; however, these biomarkers suffer from a lack of high specificity. Moreover, determining the exact type of disorder for patients with positive liquid biopsy tests is difficult, especially when the aberrant expression of one single biomarker can be found in various other disorders. In this study, a SERS-based protein biomarker detection platform in a microfluidic chip and two machine learning algorithms (K-nearest neighbor and classification tree) are used to improve the reproducibility and specificity of the SERS-based liquid biopsy assay. Applying machine learning algorithms to the analysis of the expression level data of 5 protein biomarkers (CA19-9, HE4, MUC4, MMP7, and mesothelin) in pancreatic cancer patients, ovarian cancer patients, pancreatitis patients, and healthy individuals improves the chance of recognition for one specific disorder among the aforementioned diseases with overlapping protein biomarker changes. Our results demonstrate a convenient but highly specific approach for cancer diagnostics using serum samples.
关键词： cancer biomarkers,SERS,specificity,machine learning,microfluidic
更新于2025-09-19 17:15:36
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Optical nanogap antennas as plasmonic biosensors for the detection of miRNA biomarkers
摘要： Nanoplasmonic biosensors based on nanogap antennas structures usually demand complex and expensive fabrication processes in order to achieve a good performance and sensitive detection. We here report the fabrication of large-area nanoplasmonic sensor chips based on nanogap antennas by employing a customized, simple and low-cost colloidal lithography process. By precisely controlling the angle for tilted e-beam metal evaporation, an elliptical mask is produced, which defines the total length of the dipole antenna nanostructures while assuring that the plasmonic response is oriented in the same direction along the sensor chip. Large-area sensor chips of nanogap antennas formed by pairs of gold nanodisks separated by gaps with an average size of 11.6 ± 4.7 nm are obtained. The optical characterization of the nanogap antenna structures in an attenuated total reflection (ATR) configuration shows a bulk refractive index sensitivity of 422 nm/RIU, which is in agreement with FDTD numerical simulations. The biosensing potential of the cm2-sized nanostructured plasmonic sensor chips has been evaluated for the detection of miRNA-210, a relevant biomarker for lung cancer diagnosis, through a DNA/miRNA hybridization assay. A limit of detection (LOD) of 0.78?nM (5.1 ng mL-1) was achieved with no need of further amplification steps, demonstrating the high sensitivity of these plasmonic nanogap antennas for the direct and label-free detection of low molecular weight biomolecules as miRNAs.
关键词： nanoplasmonic biosensors,miRNA biomarkers,colloidal lithography,nanogap antennas,lung cancer diagnosis
更新于2025-09-19 17:13:59