Current laboratory tests for diagnosis of hepatitis B virus infection.

BACKGROUND: Hepatitis B virus (HBV) has a long history in human infectious diseases. HBV infection can progress chronically, leading to cancer. After introduction of a vaccine, the overall incidence rate of HBV infection has decreased, although it remains a health problem in many countries. PURPOSE: The aim of this review was to summarise current diagnostic efforts for HBV infection and future HBV diagnosis perspectives. METHODS: We reviewed and summarised current laboratory diagnosis related with HBV infection in clinical practice. RESULTS: There have been various serologic- and molecular-based methods to diagnose acute or chronic HBV infection. Since intrahepatic covalently closed circular DNAs (cccDNAs) function as robust HBV replication templates, cure of chronic HBV infection is limited. Recently, new biomarkers such as hepatitis B virus core-related antigen (HBcrAg) and HBV RNA have emerged that appear to reflect intrahepatic cccDNA status. These new biomarkers should be validated before clinical usage. CONCLUSION: An effective diagnostic approach and current updated knowledge of treatment response monitoring are important for HBV infection management. Brand new ultrasensitive and accurate immunologic methods may pave the way to manage HBV infection in parallel with immunotherapy era.

Fabrication of Piezo-Resistance Composites Containing Thermoplastic Polyurethane/Hybrid Filler Using 3D Printing.

In this study, 3D-printable flexible piezoresistive composites containing various amounts of cilia-like hybrid fillers were developed. In the hybrid fillers, micro-scale Cu particles with a 0D structure may allow them to easily disperse into the flexible TPU matrix. Furthermore, nanoscale multi-walled carbon nanotubes (MWCNTs) with a high aspect ratio, present on the surface of the Cu particles, form an electrical network when the polymer matrix is strained, thus providing good piezoresistive performance as well as good flowability of the composite materials. With an optimal hybrid filler content (17.5 vol.%), the 3D-printed piezoresistive composite exhibits a gauge factor of 6.04, strain range of over 20%, and durability of over 100 cycles. These results highlight the potential applications of piezoresistive pressure sensors for health monitoring, touch sensors, and electronic skin.

The characteristics of transferrin variants by carbohydrate-deficient transferrin tests using capillary zone electrophoresis.

BACKGROUND: Transferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate-deficient transferrin (CDT) test using capillary zone electrophoresis. METHODS: We retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed. RESULTS: Seventy-seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8 years, and the male-to-female ratio was 3.5:1. The most common variants were the BC variants (n = 37), followed by the CD variants (n = 27), unclear patterns (n = 7), BD variants (n = 3), CC variants (n = 2), misclassification (n = 1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n = 22, 28.6%), followed by the toxic effects of substances (n = 17, 22.1%), and mental and behavioral disorders attributable to alcohol (n = 11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n = 880, 37.1%), a personal history of suicide attempts (n = 634, 26.7%), and mental and behavioral disorders due to alcohol (n = 336, 14.2%). CONCLUSION: We analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice.

Comparison of three rapid influenza diagnostic tests with digital readout systems and one conventional rapid influenza diagnostic test.

BACKGROUND: Rapid influenza diagnostic tests (RIDTs) show variable sensitivities in clinical settings. We aimed to compare three digital RIDTs and one conventional RIDT. METHODS: We assessed 218 nasopharyngeal swabs from patients between neonates and 90 years old in 2016. Three digital RIDTs were BUDDI, Sofia Influenza A+B Fluorescence Immunoassay, Veritor System Flu A+B assay. One conventional test was the SD Bioline Influenza Ag A/B/A(H1N1/2009). All test results were compared with those from the Anyplex Flu A/B Typing Real-time Detection real-time PCR. The four RIDTs were tested with diluted solutions from the National Institute for Biological Standards and Control (NIBSC) to compare lower detection limit. Cross-reactivity of four RIDTs within other respiratory viruses was identified. RESULTS: For influenza A, BUDDI, Sofia, Veritor, and Bioline showed 87.7%, 94.5%, 87.7%, and 72.6% sensitivity, and 100%, 97.7%, 96.5%, and 100% specificity. For influenza B, BUDDI, Sofia, Veritor, and Bioline showed 81.7%, 91.7%, 81.7%, and 78.3% sensitivity, and 100%, 95.3%, 100%, and 100% specificity, respectively. Each RIDT could detect diluted NIBSC solution, according to the level of dilution and specific influenza subtypes. Cross-reactivity of four RIDTs with other respiratory viruses was not noted. CONCLUSIONS: Sofia showed the highest sensitivity for influenza A and B detection. BUDDI and Veritor showed higher detection sensitivity than a conventional RIDT for influenza A detection, but similar results for influenza B detection. Further study is needed to compare the test performance of RIDTs according to specific, prevalent influenza subtypes.

A New Bacterial Growth Graph Pattern Analysis to Improve Positive Predictive Value of Continuous Monitoring Blood Culture System.

False positive signals (FPSs) of continuous monitoring blood culture system (CMBCS) cause delayed reporting time and increased laboratory cost. This study aimed to analyze growth graphs digitally in order to identify specific patterns of FPSs and true positive signals (TPSs) and to find the method for improving positive predictive value (PPV) of FPS and TPS. 606 positive signal samples from the BACTEC FX (BD, USA) CMBCS with more than one hour of monitoring data after positive signal were selected, and were classified into FPS and TPS groups using the subculture results. The pattern of bacterial growth graph was analyzed in two steps: the signal stage recorded using the monitoring data until positive signal and the post-signal stage recorded using one additional hour of monitoring data gained after the positive signal. The growth graph before the positive signal consists of three periods; initial decline period, stable period, and steeping period. Signal stage analyzed initial decline period and stable period, and classified the graphs as standard, increasing, decreasing, irregular, or defective pattern, respectively. Then, all patterns were re-assigned as confirmed or suspicious pattern in the post-signal stage. Standard, increasing, and decreasing patterns with both initial decline period and stable period are typical patterns; irregular patterns lacking a smooth stable period and defective patterns without an initial decline period are false positive patterns. The false positive patterns have 77.2% of PPV for FPS. The confirmed patterns, showing a gradually increasing fluorescence level even after positive signal, have 97.0% of PPV for TPS.

A Heparin-Mimicking Block Copolymer Both Stabilizes and Increases the Activity of Fibroblast Growth Factor 2 (FGF2).

Fibroblast growth factor 2 (FGF2) is a protein involved in cellular functions in applications such as wound healing and tissue regeneration. Stabilization of this protein is important for its use as a therapeutic since the native protein is unstable during storage and delivery. Additionally, the ability to increase the activity of FGF2 is important for its application, particularly in chronic wound healing and the treatment of various ischemic conditions. Here we report a heparin mimicking block copolymer, poly(styrenesulfonate-co-poly(ethylene glycol) methyl ether methacrylate)-b-vinyl sulfonate) (p(SS-co-PEGMA)-b-VS, that contains a segment that enhances the stability of FGF2 and one that binds to the FGF2 receptor. The FGF2 conjugate retained activity after exposure to refrigeration (4 °C) and room temperature (23 °C) for 7 days, while unmodified FGF2 was inactive after these standard storage conditions. A cell study performed with a cell line lacking native heparan sulfate proteoglycans indicated that the conjugated block copolymer facilitated binding of FGF2 to its receptor similar to the addition of heparin to FGF2. A receptor-based enzyme-linked immunosorbant assay (ELISA) confirmed the results. The conjugate also increased the migration of endothelial cells by 80% compared to FGF2 alone. Additionally, the FGF2-p(SS-co-PEGMA)-b-VS stimulated endothelial cell sprouting 250% better than FGF2 at low concentration. These data verify that this rationally designed protein-block copolymer conjugate enhances receptor binding, cellular processes such as migration and tube-like formation, and stability, and suggest that it may be useful for applications in biomaterials, tissue regeneration, and wound healing.

Development of stapled helical peptides to perturb the Cdt1-Mcm6 interaction.

Six all-hydrocarbon-stapled Cdt1 MBD-derived peptides have been designed and synthesized to perturb the Cdt1-Mcm6 interaction, which is involved in DNA replication. Inconsistency between the helicity of the obtained peptidomimetics and their binding affinity has been observed. The helicity of 13-amino acid stapled peptides increased, while their binding to Mcm6 was decreased. On the other hand, the 30-amino acid stapled peptides exhibited decreased helicity but increased binding affinity.

Evaluation of a Rapid Immunochromatographic Treponemal Antibody Test Comparing the Treponema Pallidum Particle Agglutination Assay.

BACKGROUND: In addition to conventional tests, several methods for detection of treponema-specific antibodies in clinical settings have been recently introduced. We aim to comparatively evaluate a rapid immunochromatographic test (ICT) for Treponema pallidum specific antibody (SD Bioline Syphilis 3.0) and the T. pallidum particle agglutination (TPPA) assay. METHODS: In all, 132 serum samples from 78 syphilis patients and 54 syphilis-negative controls were analyzed. SD Bioline Syphilis 3.0 test (Standard Diagnostic, Inc., Yongin, Korea) was evaluated and compared to Serodia TPPA assay (Fujirebio, Inc., Tokyo, Japan). All discrepant results between the two assays were repeatedly tested and evaluated by the fluorescent treponemal antibody-absorption (FTA-ABS) assay. Test reproducibility and 95% limit of detection of SD Bioline Syphilis 3.0 were determined across three different lots for seven consecutive days in triplicate. Interference due to autoantibodies and pregnancy was also tested. RESULTS: Percent agreement between SD Bioline Syphilis 3.0 and TPPA assays was 99.2%. Sensitivity and specificity were 100%, respectively. In TPPA assay, test-to-test, day-to-day, and lot-to-lot variations were not identified until 1:320 titer (eightfold dilutions). There was no interference due to the presence of antinuclear antibodies or samples or pregnancy. CONCLUSIONS: Percent agreement of SD Syphilis 3.0 and TPPA was very good. Sensitivity and specificity were appropriate for T. pallidum antibody detection. Thus, a rapid ICT could be suitable for syphilis antibody detection.

False-positive results for rapid diagnostic tests for malaria in patients with rheumatoid factor.

Four different rapid diagnostic tests (RDTs) for malaria were evaluated by testing 82 healthy control patients, 89 Plasmodium vivax-infected patients, and 92 rheumatoid factor (RF)-positive nonmalaria patients. The false-positive rate ranged from 2.2% to 13% in RF-positive patients. High RF levels are associated with malaria RDT false positivity.

Evaluation of D-dimer and prothrombin time in alcohol related liver cirrhosis with comparison of machine learning analyses.

OBJECTIVES: Liver cirrhosis (LC) can be caused by obesity, alcohol consumption, viral infection, and autoimmune disease. Early diagnosis and management of LC is important for patient quality of life. Non-invasive diagnostic methods are useful for predicting the current status and mortality risk of LC. The purpose of this study is to identify relevant diagnostic factors measured in routine laboratory test of alcohol-related liver cirrhosis (ALC) patients. METHODS: This study analyzed data from 127 patients with ALC, including their laboratory test results and clinical information, including coagulation parameters, hematologic parameters, and biochemical parameters. These data were used to compare the performance of the prediction models from three machine learning algorithms including K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF). RESULTS: Higher Model for End-stage Liver Disease (MELD) score were associated with prothrombin time (PT) and D-dimer. Logistic and multiple linear regression analyses revealed significant factors predicting mortality in the MELD group. Machine learning approaches were used to predict death in ALC patients using some laboratory parameters associated with mortality. The prediction model based on SVM exhibited better prediction performance than others. CONCLUSION: PT and D-dimer were the factors that were most strongly associated with 90-day mortality, and machine learning methods can create prediction models with good predictive power.

Whole-Exome Sequencing and Analysis of the T Cell Receptor ß and γ Repertoires in Rheumatoid Arthritis.

This study investigated the potential genetic variants of rheumatoid arthritis (RA) using whole-exome sequencing (WES) and evaluated the disease course using T cell receptor (TCR) repertoire analysis. Fourteen patients with RA and five healthy controls (HCs) were enrolled. For the RA patient group, only treatment-naïve patients were recruited, and data were collected at baseline as well as at 6 and 12 months following the initiation of the disease-modifying antirheumatic drug (DMARD) treatment. Laboratory data and disease parameters were also collected. Genetic variants were detected using WES, and the diversity of the TCR repertoire was assessed using the Shannon-Wiener diversity index. While some variants were detected by WES, their clinical significance should be confirmed by further studies. The diversity of the TCR repertoire in the RA group was lower than that in the HCs; however, after DMARD treatment, it increased significantly. The diversity was negatively correlated with the laboratory findings and disease measures with statistical significance. Variants with a potential for RA pathogenesis were identified, and the clinical significance of the TCR repertoire was evaluated in Korean patients with RA. Further studies are required to confirm the findings of the present study.

Evaluation of Analytical Performances and Comparison of 3 NT-proBNP Assays for Diagnosing Heart Failure.

CONTEXT.­: The N-terminal prohormone of the brain natriuretic peptide (NT-proBNP) is a major diagnostic biomarker for heart failure. OBJECTIVE.­: To compare the analytical and clinical performance of 3 NT-proBNP immunoassays: the Atellica IM NT-proBNP assay (Siemens Healthcare Diagnostics), the Alere NT-proBNP assay (Abbott Laboratories), and the Elecsys proBNP II assay (Roche Diagnostics). DESIGN.­: For the Atellica IM NT-proBNP assay, analytical performance, including precision, linearity, and carryover, was fully evaluated. Method comparisons among the 3 assays were performed using the Passing-Bablok regression and the κ agreement test. To evaluate the clinical performance of the assays, 160 patient samples were used from patients with (n = 81) or without (n = 79) heart failure. RESULTS.­: The analytical performance of the Atellica IM NT-proBNP assay was acceptable according to the manufacturer's claims. The Atellica IM NT-proBNP assay showed a positive bias compared with the Elecsys proBNP II assay. The Cohen κ values among the 3 assays were satisfactory (>0.80) and comparable. There were no significant differences in areas under the curve. However, for the diagnosis of heart failure, the Elecsys proBNP II showed a higher specificity and positive likelihood ratio than the other assays. CONCLUSIONS.­: All 3 NT-proBNP assays showed acceptable concordance, and their clinical performance was comparable. However, the Elecsys proBNP II might be a more discriminating NT-proBNP assay to diagnose heart failure.

Roles and correlations of TIM-3 and LAG-3 with cytokines and chemokines in alcoholic liver disease.

BACKGROUND: Dysregulation of immune checkpoint regulators has been reported in alcoholic liver disease (ALD). This study was designed to assess the serum levels of cytokines and chemokines associated with ALD and uncover the possible disease correlations with the soluble TIM-3 and LAG-3. METHODS: The soluble TIM-3 and LAG-3 levels were measured by enzyme-linked immunoassay, and 14 cytokines and chemokines were measured using Luminex-based multiplex assay in 111 male ALD patients and 45 healthy controls (HCs). RESULTS: Our results showed that soluble TIM-3 was significantly increased (p < 0.001) while soluble LAG-3 was significantly decreased (p < 0.001) in ALD group compared to HCs. Among the 14 cytokines and chemokines assessed, granulocyte-colony stimulating factor (G-CSF) (p = 0.003) and interferon γ-induced protein (IP)-10 (p < 0.001) were significantly increased, while interleukin (IL)-4 (p = 0.005) and IL-12 (p40) (p = 0.001) were significantly decreased in the ALD group. Kaplan-Meier analysis showed that overall survival decreased in higher TIM-3 level individuals. CONCLUSIONS: Our results showed that TIM-3, LAG-3, and IP-10 appear to be important for clinical diagnosis of ALD and ALD severity and may represent potential therapeutic targets in ALD.

Performance Comparison of Procalcitonin, Delta Neutrophil Index, C-Reactive Protein, and Serum Amyloid A Levels in Patients with Hematologic Diseases.

(1) Background: We compared the diagnostic and prognostic performance of serum amyloid A (SAA), procalcitonin (PCT), delta neutrophil index (DNI), and C-reactive protein (CRP) in patients with hematologic diseases; (2) Methods: We retrospectively collected the remaining serum samples from patients with hematologic diseases, analyzed their clinical data, and measured the levels of PCT, DNI, CRP, and SAA. Performances for infection diagnosis were evaluated using a receiver operating characteristic curve analysis, and 90-day mortality was analyzed using Kaplan-Meier estimation; (3) Results: The levels of all markers were significantly higher in the infected group (N = 27) than those in the uninfected group (N = 100) (p < 0.0001 for all markers). The areas under the curve for diagnosing infection for PCT, DNI, CRP, and SAA were 0.770, 0.817, 0.870, and 0.904, respectively. Increased PCT levels were associated with higher mortality (p = 0.0250); this association was not observed with other examined markers; (4) Conclusions: CRP and SAA exhibited greater discriminative power for infection than PCT. However, only PCT levels were positively associated with 90-day mortality. Herein, we evaluated the diagnostic performance of the four markers. Additional studies are needed to confirm the findings of the present study and validate the potential of these markers in clinical practice.

Bavachin and Corylifol A Improve Muscle Atrophy by Enhancing Mitochondria Quality Control in Type 2 Diabetic Mice.

Type 2 diabetes reduces muscle mass and function. Chronic inflammation and mitochondrial dysfunction play critical roles in muscle atrophy pathogenesis. Here, we investigated the effects of bavachin and corylifol A from Psoralea corylifolia L. seeds on muscle atrophy in dexamethasone-treated mice and in db/db mice. Bavachin and corylifol A enhanced muscle strength and muscle mass in dexamethasone-treated mice. In diabetic mice, they enhanced muscle strength and cross-sectional areas. Bavachin and corylifol A suppressed inflammatory cytokine (interleukin-6 and tumor necrosis factor-α) expression levels by downregulating nuclear factor-κB phosphorylation. They decreased the muscle atrophic factor (myostatin, atrogin-1, and muscle RING finger-1) expression levels. They activated the AKT synthetic signaling pathway and induced a switch from fast-type glycolytic fibers (type 2B) to slow-type oxidative fibers (types I and 2A). They increased mitochondrial biogenesis and dynamic factor (optic atrophy-1, mitofusin-1/2, fission, mitochondrial 1, and dynamin 1-like) expression levels via the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1-alpha signaling pathway. They also improved mitochondrial quality by upregulating the mitophagy factor (p62, parkin, PTEN-induced kinase-1, and BCL2-interacting protein-3) expression levels. Therefore, bavachin and corylifol A exert potential therapeutic effects on muscle atrophy by suppressing inflammation and improving mitochondrial function.

Engineered molecular stacking crystallinity of bar-coated TIPS-pentacene/polystyrene films for organic thin-film transistors.

Solution-based blended polymer materials are promising for electronic applications in many fields. However, determining a controllable method to achieve electronically active organic films through the practical liquid deposition process is very challenging. In this study, we suggest employing hybrid binary organic mixture inks (an insulating polymer polystyrene (PS)) and an organic semiconductor (6,13-bis(triisopropylsilylethnyl)pentacene (TIPS-pentacene)) to manage and enhance the characteristics of TIPS-pentacene organic layers using a bar-coating method. Binary mixtures with PS molecules can provide various microstructures, crystal orientations, and molecular stacking of the active TIPS-pentacene organic layers under the proper fabrication parameters during bar-coating. Varying the molecular weight of the PS mixture, weight percentage of the TIPS-pentacene, and deposition parameters, such as the bar-coating speed, direction, and contact angles between the crystal orientation of TIPS-pentacene and Au electrodes, is crucial to guarantee high-electronic properties. The electrodes with TIPS-pentacene/PS (MW = 4000) binary films at a 40 wt% TIPS-pentacene ratio demonstrate the outstanding room-temperature field-effect mobility of 1.215 cm2 V-1 s-1, four times higher than that of pure TIPS-pentacene transistors (100 wt%). The performance improvement of the TIPS-pentacene layers is highly attributed to the ideal spherulite structure and thick molecular stacking properties, which can guarantee favorable charge transport paths through organic films. These findings demonstrate a promising strategy for blending organic applications to improve the performance of organic electronic devices using practical fabrication processes.

Reference ranges for HE4 and CA125 in a large Asian population by automated assays and diagnostic performances for ovarian cancer.

Human epididymis protein 4 (HE4) is a new biomarker for the detection of ovarian cancer. We evaluated the analytical performance of a novel automated HE4 assay and established reference ranges of HE4 and CA125. We also compared the diagnostic performance of both biomarkers for ovarian cancer. Precision performances and linearity of the HE4 assay were assessed. Serum samples from 2,182 healthy and 72 pregnant women were also assayed for HE4 and CA125, and the 95%, 97.5% and 99% reference limits for both markers were calculated. Additionally, sera from 66 ovarian cancer and 257 benign gynecologic disease patients were tested to validate reference ranges and diagnostic performances. The total precision of the HE4 assay was <5% coefficient of variation for most of the levels evaluated. The linearity range of this assay was from 15.0 to 1100.0 pmol/L. The 97.5% upper reference limits for HE4 and CA125 were 33.2 pmol/L (95% confidence interval [CI], 32.2-34.0) and 38.3 U/mL (95% CI, 35.1-41.5), respectively. Using these values as cutoff points, the sensitivity and specificity of HE4 for differentiating ovarian cancer from benign gynecologic diseases and healthy individuals were 90.9% and 94.1%, and those of CA125 were 72.7% and 94.4%. The receiver operating characteristic-area under the curve values of HE4 and CA125 for discriminating ovarian cancer from age-matched control were 0.94 and 0.86, respectively, and they were statistically different (p = 0.0095). The new automated HE4 assay showed good analytical and diagnostic performances. The reference limits established in our study could be used as cutoff levels to facilitate more accurate diagnosis of ovarian cancer in Asian population.

A synchronized multipoint vision-based system for displacement measurement of civil infrastructures.

This study presents an advanced multipoint vision-based system for dynamic displacement measurement of civil infrastructures. The proposed system consists of commercial camcorders, frame grabbers, low-cost PCs, and a wireless LAN access point. The images of target panels attached to a structure are captured by camcorders and streamed into the PC via frame grabbers. Then the displacements of targets are calculated using image processing techniques with premeasured calibration parameters. This system can simultaneously support two camcorders at the subsystem level for dynamic real-time displacement measurement. The data of each subsystem including system time are wirelessly transferred from the subsystem PCs to master PC and vice versa. Furthermore, synchronization process is implemented to ensure the time synchronization between the master PC and subsystem PCs. Several shaking table tests were conducted to verify the effectiveness of the proposed system, and the results showed very good agreement with those from a conventional sensor with an error of less than 2%.

A vision-based dynamic rotational angle measurement system for large civil structures.

In this paper, we propose a vision-based rotational angle measurement system for large-scale civil structures. Despite the fact that during the last decade several rotation angle measurement systems were introduced, they however often required complex and expensive equipment. Therefore, alternative effective solutions with high resolution are in great demand. The proposed system consists of commercial PCs, commercial camcorders, low-cost frame grabbers, and a wireless LAN router. The calculation of rotation angle is obtained by using image processing techniques with pre-measured calibration parameters. Several laboratory tests were conducted to verify the performance of the proposed system. Compared with the commercial rotation angle measurement, the results of the system showed very good agreement with an error of less than 1.0% in all test cases. Furthermore, several tests were conducted on the five-story modal testing tower with a hybrid mass damper to experimentally verify the feasibility of the proposed system.