Early Diagnosis Of Several Diseases Research Articles

Molecularly Imprinted Polymer Interface on Screen-Printed ZnO Nanorod Field Effect Transistors for Serotonin Detection in Clinical Samples.

Ultrasensitive detection of serotonin is crucial for the early diagnosis of several diseases like Parkinson's and Alzheimer's. Most of the existing detection strategies are still not suitable for sensitive point-of-care applications. This study presents direct molecular imprinting of serotonin on the surface of three-dimensional zinc oxide (ZnO) nanorod devices connected in a field effect transistor (FET) configuration to achieve ultrasensitive, real-time, and rapid detection with a convenient and affordable approach, which has significant potential for translation to clinical settings. This strategy has enabled pushing the detection limit to 0.1 fM in a physiological analyte in real time with screen-printed electrodes, thereby resulting in the convenient batch fabrication of sensors for clinical validation. The response of the sensor with the clinical sample has been correlated with that of the gold standard and has been observed to be statistically similar.

Identifying elevated plasma free triiodothyronine levels: age-adapted reference intervals for pediatrics.

Elevated free T3 (FT3) is an important feature for the early diagnosis of several diseases among which Grave's disease or Allan-Hernon-Dudley syndrome. However, there is a lack of age-adapted reference intervals for plasma thyroid hormones in children. We conducted a study to define reference values of peripheral FT3 in children using a commonly used automated immunoassay. All thyroid function test (TFT) results from our lab collected during 9 months were extracted anonymously, and reference intervals establishment followed recommendations validated by International Federation of Clinical Chemistry (IFCC). We defined five reference intervals covering the whole pediatric period. Overall, 26.1% of peripheral FT3 measured in children with normal TSH are out of the adult reference range, and 22.2% are upper it leading to misinterpretation. In a 9-month old patient with severe neurodevelopmental disorders, a pathological elevated FT3 has been securely interpreted using the newly established interval. The study highlights the poor relevance of adult intervals in pediatric cares, as it confirms that plasmatic FT3 is higher during the whole pediatric period. This work reports useful age-adapted reference intervals for free T3 in pediatrics using a widely used electrochemiluminescent Immunoassay (ECLIA) kit.

Proteolytic Biosensors with Functional Nanomaterials: Current Approaches and Future Challenges.

Proteolytic enzymes are one of the important biomarkers that enable the early diagnosis of several diseases, such as cancers. A specific proteolytic enzyme selectively degrades a certain sequence of a polypeptide. Therefore, a particular proteolytic enzyme can be selectively quantified by changing detectable signals causing degradation of the peptide chain. In addition, by combining polypeptides with various functional nanomaterials, proteolytic enzymes can be measured more sensitively and rapidly. In this paper, proteolytic enzymes that can be measured using a polypeptide degradation method are reviewed and recently studied functional nanomaterials-based proteolytic biosensors are discussed. We anticipate that the proteolytic nanobiosensors addressed in this review will provide valuable information on physiological changes from a cellular level for individual and early diagnosis.

The New Era of Salivaomics in Dentistry: Frontiers and Facts in the Early Diagnosis and Prevention of Oral Diseases and Cancer.

Nowadays, with the development of new and highly sensitive, blood is not the only medium of choice for the diagnosis of several diseases and pathological conditions. Saliva is now considered a safe and non-invasive sample to study oral and systemic diseases, showing great diagnostic potential. According to several recent studies, saliva has emerged as an emerging biofluid for the early diagnosis of several diseases, indicated as a mirror of oral and systemic health and a valuable source of clinically relevant information. Indeed, several studies have observed that saliva is useful for detecting and diagnosing malignant tumours, human immunodeficiency virus, heart disease, and autoimmune diseases. The growing realisation that saliva is an inexhaustible source of information has led to the coining of the term ‘Salivaomics’, which includes five “omics” in connection with the main constituents of saliva: genome and epigenome, transcriptomics, metabolomics, lipidomics, proteomics and microbiota. All those may be changed by disease state, so they offer significant advantages in the early diagnosis and prognosis of oral diseases. The aim of the present review isto update and highlight the new frontiers of salivaomics in diagnosing and managing oral disorders, such as periodontitis, premalignant disorders, and oral squamous cell carcinoma (OSCC).

Application of Machine Learning for Accurate Detection of Hemoglobin Concentrations Employing Defected 1D Photonic Crystal

Realizing the significance of precise detection of hemoglobin concentrations towards early diagnosis of several diseases, the present work addresses design and analysis of hemoglobin sensor based on the defective 1D photonic crystal (PhC). The alternating layers of Si and SiO2 are used to design the proposed PhC with a central defect layer infiltrated with hemoglobin concentrations. The well-established transfer matrix method (TMM) is manipulated to study the transmission spectrum of the structure. The strong dependence of defect mode characteristics on the refractive index of the hemoglobin concentrations forms the backbone of this work. Numerous geometrical parameters such as thickness of defect layer, angle of incidence are meticulously optimized to realize high sensitivity. Additionally, the effect of temperature is thoroughly investigated on the sensing performance. It is perceived that at an incident angle of 300 and the defect layer thickness of 550 nm, the proposed structure bestows a maximum sensitivity of 1916.77 nm/RIU. Finally, we developed a machine learning model to predict different concentrations of hemoglobin in blood, where we found that the model output is closely matched with the output obtained through the TMM. Moreover, it is perceived that the developed machine learning model can predict hemoglobin concentrations with high accuracy and linearity.

Microfluidics-Integrated Sensors toward Rapid Detection of Single Nucleotide Variations.

Rapid detection of single nucleotide variations (SNVs) is of critical importance to early diagnosis of several diseases and the prediction of diverse responses to a specific treatment. Based on the information published in the literature, discrimination of SNVs is a developing area of study with great research enthusiasm and is also an area that can benefit from microfluidics-integrated designs. This review provides a brief overview of different microfluidics-based strategies for rapid detection of SNVs and mismatched bases. Sensors based on various microfluidic formats, such as paper-based microfluidic biosensors, droplet-based microfluidic systems, and magnetic bead-based microfluidic biosensors, have been discussed with respect to their specific pros and cons for SNV detection. These systems have shown promise for distributed on-site diagnostics in personalized medicine.

Human-in-the-Loop Predictive Analytics Using Statistical Learning.

The human-in-the-loop cyber-physical system provides numerous solutions for the challenges faced by the doctors or medical practitioners. There is a linear trend of advancement and automation in the medical field for the early diagnosis of several diseases. One of the critical and challenging diseases in the medical field is coma. In the medical research field, currently, the prediction of these diseases is performed only using the data gathered from the devices only; however, the human's input is much essential to accurately understand their health condition to take appropriate decision on time. Therefore, we have proposed a healthcare framework involving the concept of artificial intelligence in the human-in- the-loop cyber-physical system. This model works via a response loop in which the human's intention is concluded by gathering biological signals and context data, and then, the decision is interpreted to a system action that is recognizable to the human in the physical environment, thereby completing the loop. In this paper, we have designed a model for early prognosis of coma using the electroencephalogram dataset. In the proposed approach, we have achieved the best results using a statistical learning algorithm called autoregressive integrated moving average in comparison to artificial neural networks and long short-term memory models. In order to measure the efficiency of our model, we have used the root mean squared error (RMSE), mean absolute error (MAE), and mean squared error (MSE) value to evaluate the linear models as it gives the difference between the measured value and true or correct value. We have achieved the least possible error value for our dataset. To conduct this experiment, we used the dataset available in the phsyionet opensource community.

Early immune responses and prognostic factors in children with COVID-19: a single-center retrospective analysis

BackgroundEarly diagnostic indicators and the identification of possible progression to severe or critical COVID-19 in children are unknown. To investigate the immune characteristics of early SARS-CoV-2 infection in children and possible key prognostic factors for early identification of critical COVID-19, a retrospective study including 121 children with COVID-19 was conducted. Peripheral blood lymphocyte subset counts, T cell-derived cytokine concentrations, inflammatory factor concentrations, and routine blood counts were analyzed statistically at the initial presentation.ResultsThe T lymphocyte subset and natural killer cell counts decreased with increasing disease severity. Group III (critical cases) had a higher Th/Tc ratio than groups I and II (common and severe cases); group I had a higher B cell count than groups II and III. IL-6, IL-10, IFN-γ, SAA, and procalcitonin levels increased with increasing disease severity. Hemoglobin concentration, and RBC and eosinophil counts decreased with increasing disease severity. Groups II and III had significantly lower lymphocyte counts than group I. T, Th, Tc, IL-6, IL-10, RBC, and hemoglobin had relatively high contribution and area under the curve values.ConclusionsDecreased T, Th, Tc, RBC, hemoglobin and increased IL-6 and IL-10 in early SARS-CoV-2 infection in children are valuable indices for early diagnosis of severe disease. The significantly reduced Th and Tc cells and significantly increased IL-6, IL-10, ferritin, procalcitonin, and SAA at this stage in children with critical COVID-19 may be closely associated with the systemic cytokine storm caused by immune dysregulation.

The Luminescence of 1,8-Diazafluoren-9-One/Titanium Dioxide Composite Thin Films for Optical Application.

The investigation of innovative label-free α-amino acids detection methods represents a crucial step for the early diagnosis of several diseases. While 1,8-diazafluoren-9-one (DFO) is known in forensic application because of the fluorescent products by reacting with the amino acids present in the papillary exudate, its application for diagnostic purposes has not been fully investigated. The stabilization of DFO over a transparent substrate allows its complexation with biomolecules for the detection of α-amino acids. In this study, DFO was immobilized into a titanium dioxide (TiO2) matrix for the fluorescence detection of glycine, as a target α-amino acid (a potential marker of the urogenital tract cancers). The DFO/TiO2 composite was characterized by atomic force microscopy, spectroscopic ellipsometry, fluorescence spectroscopy and fluorescence microscopy. The performed fluorescent studies indicate spectacular formation of aggregates at higher concentration. The measurements performed using various fluorescence and microscopic techniques together with the suitable analysis show that the aggregates are able to emit short-lived fluorescence.

Noble Metal-Assisted Surface Plasmon Resonance Immunosensors.

For the early diagnosis of several diseases, various biomarkers have been discovered and utilized through the measurement of concentrations in body fluids such as blood, urine, and saliva. The most representative analytical method for biomarker detection is an immunosensor, which exploits the specific antigen-antibody immunoreaction. Among diverse analytical methods, surface plasmon resonance (SPR)-based immunosensors are emerging as a potential detection platform due to high sensitivity, selectivity, and intuitive features. Particularly, SPR-based immunosensors could detect biomarkers without labeling of a specific detection probe, as typical immunosensors such as enzyme-linked immunosorbent assay (ELISA) use enzymes like horseradish peroxidase (HRP). In this review, SPR-based immunosensors utilizing noble metals such as Au and Ag as SPR-inducing factors for the measurement of different types of protein biomarkers, including viruses, microbes, and extracellular vesicles (EV), are briefly introduced.

Highly sensitive surface-enhanced Raman spectroscopy (SERS) platform using core/double shell (Ag/polymer/Ag) nanohorn for proteolytic biosensor

Sensitive detection platforms have recently gathered more interest due to its ability to make an early diagnosis of several diseases, which increases the chances of successful treatment. Although several highly sensitive platforms have been developed, improvements are needed to reduce their reaction time and cost. In this study, we established a surface-enhanced Raman spectroscopy (SERS)-based ultrasensitive platform by using SERS-active hollow polypyrrole (hPPy) nanohorn and peptide-functionalized gold nanoparticles (AuNPs). To create a SERS-active platform, we deposited silver on the inside and outside of the hPPy nanohorn surface; this resulted in the formation of core/double-shells Ag/polymer/Ag nanostructures. In addition, peptide-functionalized AuNPs functionalized with Raman dye was pre-immobilized on the Ag/hPPy/Ag nanohorn to enhance the signals and skip additional steps for the biomolecular detection. Using this SERS-sensitive novel core/double-shell nanohorn platform, we enhanced the Raman signal and improved the sensitivity of caspase-3, which is associated with several diseases, and achieved a broad detection range from 10 pg/ml to 10 µg/ml. We suggest that the highly sensitive and simple detection of this nanohorn platform can be widely applied for sensitive detection of proteolytic biomarkers and early diagnosis of several diseases.

Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1α-VEGF signaling pathway.

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p < 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p < 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.

Multi-expert analysis and validation of objective vascular tortuosity measurements

The retinal vascular tortuosity is a commonly used parameter for the early diagnosis of several diseases that affects the circulatory system. The manual analysis of fundus images for the tortuosity characterization is a time-consuming and subjective task that presents a high inter-rater variability. Thus, automatic image processing methods allow the efficient computation of objective and stable parameters for the issue. The validation of these methods is crucial to ensure an objective and reliable environment for the retinal experts. This paper describes a multi-expert analysis that measures the clinical performance as well as a validation procedure of the computational tortuosity module of the Sirius framework, a computer-aided diagnosis platform for analyzing retinal images.

An Online Electrochemical System for Continuously Monitoring Uric Acid Change following Rabbit Kidney following Ischemia-reperfusion Injury

In vivo monitoring of uric acid (UA) with high reliability and robustness is of great physiological and pathological importance because UA, as one kind of the most important chemical species in the biological systems, plays a great role in some physiological processes and is used as the biomarkers for early diagnosis of several diseases. In this study, a microfluidic chip-based online electrochemical system (OECS) is developed for the first time for continuously monitoring UA in rabbit kidney. To establish the OECS for UA monitoring, a single-channel microfluidic chip is developed into an electrochemical cell by incorporating a single-walled carbon nanotubes (SWNTs)-modified indium-tin oxide (ITO) electrode as working electrode, an Ag/AgCl wire as reference electrode, and a Pt tube as counter electrode. To completely remove ascorbic acid and thus eliminate its interference toward UA detection in such a single-channel microfluidic chip, ascorbate oxidase (AOx) is crosslinked onto both the etched ITO glass in the upstream channel and the SWNT-modified ITO electrode in the downstream. With the as-prepared microfluidic chip-based electrochemical cell as the detector for selective detection of UA, an online electrochemical system is successfully established by directly coupling the microfluidic chip-based electrochemical detector with in vivo microdialysis. The system exhibits a good linear response, high stability and good in vivo selectivity and is thus able to continuously sense UA change in rabbit kidney following ischemia-reperfusion injury. The study essentially offers a new OECS for in vivo continuous monitoring of UA.

Determination of 4-hydroxy-2-nonenal in serum by high-performance liquid chromatography with fluorescence detection after pre-column derivatization using 4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2, 1,3-benzoxadiazole.

4-Hydroxy-2-nonenal (4HNE) is a major aldehyde generated during lipid peroxidation. The clinical monitoring of 4HNE in biological fluids should be useful for the early diagnosis of several diseases involving lipid peroxidation, such as rheumatoid arthritis, Parkinson's disease and cancer. In this study, an HPLC with fluorescence detection method was developed for the determination of 4HNE in human serum. The proposed method involves the extraction of 4HNE from human serum by sub-zero temperature extraction and fluorescent labeling of 4HNE with 4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2, 1,3-benzoxadiazole. The lower detection limit (signal-to-noise ratio = 3) of the method was 0.06 μm in serum. The proposed method was successfully applied to the measurement of 4HNE in sera obtained from patients with rheumatoid arthritis.

Low Urine Vascular Endothelial Growth Factor Levels Are Associated with Mechanical Ventilation, Bronchopulmonary Dysplasia and Retinopathy of Prematurity

Background: Organ-specific vascular endothelial growth factor (VEGF) expression is decreased during the pathogenesis of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) several weeks before either disease can be diagnosed. Early measurement of organ-specific tissue VEGF levels might allow identification of infants at high risk for these diseases, but is not clinically feasible. Urine VEGF is easily measured and useful in early diagnosis of several diseases. Objectives: Our aims were to assess the correlation of urine VEGF levels measured in the first postnatal month with subsequent BPD or ROP diagnosis and to determine whether various infant characteristics influence urine VEGF levels. Methods: 106 subjects born at <29 weeks' gestation and surviving to 36 weeks' postmenstrual age were selected from an existing database and biorepository. Urine VEGF and total protein were measured in 2-3 samples per subject. Results: Urine VEGF/protein levels increased by 72% per week (p < 0.0001) during the first postnatal month. In multivariable analysis controlling for postnatal age, lower VEGF/protein was associated with higher levels of mechanical respiratory support (p = 0.006), male gender (p = 0.001) and early sepsis (p = 0.003) but not with fraction of inspired oxygen. Lower urine VEGF/protein and mechanical ventilation were each associated with BPD and ROP. In analyses adjusted for respiratory support, lower urine VEGF/protein and ROP remained associated but urine VEGF/protein and BPD did not. Conclusions: Low urine VEGF/protein levels in the first postnatal month are associated with mechanical ventilation, BPD, and ROP.

Plasma miR-601 and miR-760 Are Novel Biomarkers for the Early Detection of Colorectal Cancer

BackgroundColorectal cancer (CRC) is a major cause of death worldwide. Sensitive, non-invasive diagnostic screen methods are urgently needed to improve its survival rates. Stable circulating microRNA offers unique opportunities for the early diagnosis of several diseases, including cancers. Our aim has been to find new plasma miRNAs that can be used as biomarkers for the detection of CRC.Methodology/Principal FindingsAccording to the results of miRNA profiling performed on pooling plasma samples form 10 CRC patients or 10 healthy controls, a panel of miRNAs (hsa-miR-10a, -19a, -22*, -24, -92a, 125a-5p, -141, -150, -188-3p, -192, -210, -221, -224*, -376a, -425*, -495, -572, -601, -720, -760 and hsa-let-7a, -7e) were deregulated in CRC plasma with fold changes >5. After large scale validation by qRT-PCR performed on another 191 independent individuals (90 CRC, 43 advanced adenoma and 58 healthy participants), we found that the levels of plasma miR-601 and miR-760 were significantly decreased in colorectal neoplasia (carcinomas and advanced adenomas) compared with healthy controls. ROC curve analysis showed that plasma miR-601 and miR-760 were of significant diagnostic value for advanced neoplasia. These two miRNAs together yield an AUC of 0.792 with 83.3% sensitivity and 69.1% specificity for separating CRC from normal controls, and yield an AUC of 0.683 with 72.1% sensitivity and 62.1% specificity in discriminating advanced adenomas from normal controls.Conclusions/SignificancePlasma miR-601 and miR-760 can potentially serve as promising non-invasive biomarkers for the early detection of CRC.

Selective determination of ubiquinone in human plasma by HPLC with chemiluminescence reaction based on the redox cycle of quinone

Ubiquinone is an important biologically active compound in the living body. The determination of ubiquinone in human plasma is useful for the investigation of bioavailability of ubiquinone and for early diagnosis of several diseases. Therefore, we developed a high-performance liquid chromatography (HPLC) with chemiluminescence detection method for the analysis of ubiquinone in plasma samples. The method is based on luminol chemiluminescence detection of super oxide anion that is generated by the redox cycle reaction between ubiquinone and dithiothreitol. The HPLC system involved an octyl column with a mobile phase of methanol. Ubiquinone eluted from the column was mixed with dithiothreitol and luminol solutions simultaneously, and generated chemiluminescence was monitored by chemiluminescence detector. The calibration curve for standard ubiquinone solution was linear from 0.09 to 43.2μg/mL (0.45-216ng on column) with the correlation coefficient of 0.999, and the detection limit (S/N = 3) was 26ng/mL (130pg on column). Using the proposed HPLC method, the peak of ubiquinone in human plasma could be clearly detected on the chromatogram without any interference from plasma components.

Circulating MicroRNAs are Promising Novel Biomarkers of Acute Myocardial Infarction

Recent studies have revealed that microRNAs (miRNAs) are involved in the regulation of cardiac development, physiologic, and pathologic processes via post-transcriptional control of gene expression. The stable circulating miRNAs offer unique opportunities for the early diagnosis of several diseases. In this study, we examined the circulating miR-133 and miR-328 levels from patients with acute myocardial infarction (AMI). Twenty-eight control subjects and fifty-one consecutive AMI patients were enrolled. The plasma and whole blood samples from AMI patients were obtained within 24 hours (n=51) and 7 days (n=6) after the onset of AMI symptoms. The circulating miR-133 and miR-328 levels were analyzed using quantitative real-time PCR. The miR-133 levels in plasma from AMI patients exhibited a 4.4-fold increase compared with control subjects (p=0.006). Moreover, the increased miR-133 levels in whole blood were comparable with those in plasma samples. In contrast, the miR-328 levels in plasma and whole blood of AMI patients were markedly increased by 10.9-fold and 16.1-fold, respectively, compared to those in control subjects (p=0.033 and p<0.001). The elevated circulating miR-133 and miR-328 levels were recovered to the control levels at 7 days after AMI. In addition, there was a correlation between circulating miR-133 or miR-328 levels and cardiac troponin I. Furthermore, circulating miR-133 or miR-328 showed no significant changes in AMI patients with tachyarrhythmia (n=24) or bradyarrhythmia (n=26) compared to those in patients without arrhythmias. Receiver operating characteristic curve analysis revealed that the areas under the curve of miR-133 or miR-328 in plasma and whole blood were 0.890, 0.702 and 0.810, 0.872, respectively (all p<0.05). The miR-133 and miR-328 levels in plasma and whole blood in AMI patients were increased compared to those in control subjects. These miRNAs may represent novel biomarkers of AMI.