Evaluating M2BPGi as a Marker for Liver Fibrosis in Patients with Chronic Hepatitis B.

BACKGROUND: The accurate evaluation of liver fibrosis is crucial for the treatment and follow up of chronic hepatitis B (CHB) patients. AIM: We examined the efficiency of serum Mac-2 Binding Protein Glycosylation isomer (M2BPGi) in diagnosing liver fibrosis stages in CHB patients. METHODS: A cross-sectional study was conducted on 177 adult CHB patients visiting the University Medical Center Ho Chi Minh City, Vietnam between October 2019 and December 2021. M2BPGi, ARFI, APRI, and FIB-4 were tested against FibroScan® for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The optimal M2BPGi cut-off values were identified based on the area under the receiver operating characteristic (AUROC) curve. RESULTS: There was a strong agreement between M2BPGi and FibroScan® (r = 0.77, P < 0.001). The optimal M2BPGi cut-off index (C.O.I) for detecting significant fibrosis (F ≥ 2) was 0.79 with an AUROC of 0.77, 67.3% sensitivity, 70% specificity, 60.6% NPV, and 75.3% PPV. Compared with APRI (61%) and FIB-4 (47%), M2BPGi had the greatest sensitivity for diagnosing F ≥ 2. M2BPGi combined with APRI yielded highest diagnosis performance for F ≥ 2 with an AUROC of 0.87. The optimal cut-off index of M2BPGi for diagnosing cirrhosis (F4) was 1.3 with an AUROC of 0.91, 88% sensitivity, 87.4% specificity, 97% NPV, and 61% PPV. The AUROC of M2BPGi for diagnosing F4 was comparable to that of ARFI (0.93). CONCLUSIONS: With cut-off values of 0.79 C.O.I and 1.3 C.O.I, M2BPGi could be an effective method for diagnosing significant fibrosis and cirrhosis in CHB patients, respectively.

Relative Abundance and Detection of Pseudomonas aeruginosa from Chronic Wound Infections Globally.

Pseudomonas aeruginosa is a difficult-to-treat pathogen that is frequently involved with chronic wound infections. Here, we conducted a literature search of world-wide studies published between 2005 and 2022 that described the microbiological profiles of chronic wound infections. For each continent, a hierarchy of pathogens was created to define the organisms that were most frequently isolated in each region. Except for South America, P. aeruginosa was the second most common organism in each major continent, with Staphylococcus aureus being the most abundant pathogen overall. When individual countries were evaluated, P. aeruginosa was the most frequently isolated organism in several Southeast Asia nations including India and Malaysia. P. aeruginosa was less commonly isolated from diabetic foot infections in North America, Europe, and Africa in comparison to other types of chronic wound infections. Additionally, the Levine wound swab technique may be a quick and painless way to isolate P. aeruginosa from wound infections, but the isolation of P. aeruginosa does not seem to be an informative predictor of the patient's clinical course. A multivariate risk assessment that accounts for the regional frequency of P. aeruginosa isolation may be an appropriate way to guide empiric management of chronic wound infections.

Diagnostic Performance of Acoustic Radiation Force Impulse Imaging in Evaluating Liver Fibrosis in Patients with Chronic Hepatitis B Infection: A Cross-Sectional Study.

Background Acoustic radiation force impulse point shear wave elastography (ARFI-pSWE), measuring shear-wave velocity (SWV), has been utilized to examine the liver stiffness caused by different etiologies. However, information on its reliability in staging liver fibrosis in chronic hepatitis B (CHB) patients is scarce. Purpose The aim of the study is to examine the diagnostic performance of ARFI-pSWE and determine the optimal SWV cut-off values to predict significant fibrosis ( F ≥2) and cirrhosis (F4) in CHB patients. Material and Methods All 114 adult CHB patients visiting the University Medical Center, Ho Chi Minh City, Vietnam between February 2019 and March 2021 underwent liver stiffness measurement using ARFI-pSWE and FibroScan. SWV results were tested against FibroScan for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The area under the receiver operating characteristic (AUROC) curve was used to identify the optimal SWV cut-off values. Results There was a strong agreement between ARFI-pSWE and FibroScan ( r = 0.92, p <0.001). The optimal SWV cut-off value for detecting significant fibrosis was 1.37 m/s with an AUROC of 0.975, sensitivity of 83.3%, specificity of 100%, PPV of 100%, and NPV of 81%. The optimal cut-off value for predicting cirrhosis was 1.70 m/s with an AUROC of 0.986, sensitivity of 97%, specificity of 93%, PPV of 95%, and NPV of 96%. Conclusion ARFI-pSWE could be an effective technique for evaluating liver fibrosis in CHB patients. SWV cut-off values of 1.37 and 1.70 m/s could be used to diagnose significant fibrosis and cirrhosis, respectively.

Dedifferentiation of Human Cardiac Myofibroblasts Is Independent of Activation of COX-2/PGE2 Pathway.

The differentiation of cardiac fibroblasts to myofibroblasts is considered to be a critical step in activation and progression of cardiac fibrosis in heart disease. TGF-ß is one of the key cytokines that promotes transition of fibroblasts to myofibroblasts. Dedifferentiation of formed myofibroblasts or reversal of formed myofibroblasts to fibroblasts remains incompletely understood. Prostaglandin E2 (PGE2) has been shown to dedifferentiate human lung myofibroblasts. The role of activation of the COX-2/PGE2 pathway in dedifferentiation of cardiac myofibroblasts remains unknown. Here, we show that phorbol 12-myristate 13-acetate (PMA) but not PGE2 induces dedifferentiation of de novo adult human cardiac myofibroblasts stimulated by TGF-ß1 from human cardiac fibroblasts as evidenced by reduced expression of α-smooth muscle actin (α-SMA). PMA remarkably increased endogenous levels of PGE2 in human cardiac myofibroblasts. Pretreatment of myofibroblasts with NS-398, a selective COX-2 inhibitor, and PF-04418948, a selective PGE2 receptor type 2 (EP2) antagonist, had no effect on expression of α-SMA nor abolished the dedifferentiation induced by PMA. Our results indicated that endogenous and exogenous PGE2 has no effects on dedifferentiation of cardiac myofibroblasts. PMA-induced dedifferentiation of cardiac myofibroblast is independent of activation of COX-2 and PGE2 pathway. The mechanism in PMA-induced reversal of cardiac myofibroblasts needs to be explored further.

Impact of an extreme monsoon on CO2 and CH4 fluxes from mangrove soils of the Ayeyarwady Delta, Myanmar.

Mangrove ecosystems can be both significant sources and sinks of greenhouse gases (GHGs). Understanding variability in flux and the key factors controlling emissions in these ecosystems are therefore important in the context of accounting for GHG emissions. The current study is the first to quantify GHG emissions using static chamber measurements from soils in disused aquaculture ponds, planted mangroves, and mature mangroves from the Ayeyarwady Delta, Myanmar. Soil properties, biomass and estimated net primary productivity were also assessed. Field assessments were conducted at the same sites during the middle of the dry season in February and end of the wet season in October 2019. Rates of soil CO2 efflux were among the highest yet recorded from mangrove ecosystems, with CO2 efflux from the 8 year old site reaching 86.8 ± 17 Mg CO2 ha-1 yr-1 during February, an average of 862% more than all other sites assessed during this period. In October, all sites had significant rates of soil CO2 efflux, with rates ranging from 31.9 ± 4.4 Mg CO2 ha-1 yr-1 in a disused pond to 118.9 ± 24.3 Mg CO2 ha-1 yr-1 in the 8 year old site. High soil CO2 efflux from the 8 year old site in February is most likely attributable to high rates of primary production and belowground carbon allocation. Elevated CO2 efflux from all sites during October was likely associated with the extreme 2019 South Asian monsoon season which lowered soil pore salinity and deposited new alluvium, stimulating both autotrophic and heterotrophic activity. Methane efflux increased significantly (50-400%) during the wet season from all sites with mangrove cover, although was a small overall component of soil GHG effluxes during both measurement periods. Our results highlight the critical importance of assessing GHG flux in-situ in order to quantify variability in carbon dynamics over time.

Conformational Free-Energy Differences of Large Solvated Systems with the Focused Confinement Method.

The focused confinement method (FCM) is a reaction coordinate-free simulation approach for the calculation of conformational free-energy differences in explicit solvent. The method uses reference states for the conformations of interest, partitions the solute into conformationally active and inactive regions, and requires the calculation of desolvation free energies of mixed harmonic-anharmonic states as part of its procedure. The reference states and partitioning affect the speed of convergence of FCM's constituent simulations in opposing manners, but in the thermodynamic limit, they have no effect on calculated conformational free-energy differences. To aid fast convergence of large systems, a general procedure to quickly partition and construct reference states is introduced. With this, two sets of reference states and associated partitionings were constructed for the closed and open conformation of triosephosphate isomerase (TIM). Despite TIM's size, highly converged desolvation free energies were readily obtained from standard free-energy perturbation simulations because the mixed harmonic-anharmonic states are heavily rigidified. FCM-calculated free-energy differences for loop closing matched the experimental value for both reference sets. The insensitivity to reference states and associated partitionings favors reference states that merely reflect main structural differences for which convergence is faster. The calculations demonstrate the accuracy and robustness of FCM for large systems.

Calculation of Conformational Free Energies with the Focused Confinement Method.

We introduce the focused confinement method, a reaction coordinate-free simulation approach for the calculation of conformational free energies. These are obtained in a series of restrained simulations that transform part of the molecule of interest to independent harmonic oscillators resulting in mixed harmonic-anharmonic states. It is shown that the free energy difference between these mixed states can be readily calculated through the construction of chimeric trajectories. By focusing the confinement to the conformationally active region, the method requires fewer restrained simulations than the traditional confinement method, which eases the treatment of large systems. The accuracy and efficiency of the method is demonstrated for implicitly and explicitly solvated systems.

Evaluation of deep convolutional neural networks for glaucoma detection.

PURPOSE: To investigate the performance of deep convolutional neural networks (DCNNs) for glaucoma discrimination using color fundus images STUDY DESIGN: A retrospective study PATIENTS AND METHODS: To investigate the discriminative ability of 3 DCNNs, we used a total of 3312 images consisting of 369 images from glaucoma-confirmed eyes, 256 images from glaucoma-suspected eyes diagnosed by a glaucoma expert, and 2687 images judged to be nonglaucomatous eyes by a glaucoma expert. We also investigated the effects of image size on the discriminative ability and heatmap analysis to determine which parts of the image contribute to the discrimination. Additionally, we used 465 poor-quality images to investigate the effect of poor image quality on the discriminative ability. RESULTS: Three DCNNs showed areas under the curve (AUCs) of 0.9 or more. The AUC of the DCNN using glaucoma-confirmed eyes against nonglaucomatous eyes was higher than that using glaucoma-suspected eyes against nonglaucomatous eyes by approximately 0.1. The image size did not affect the discriminative ability. Heatmap analysis showed that the optic disc area was the most important area for the discrimination of glaucoma. The image quality affected the discriminative ability, and the inclusion of poor-quality images in the analysis reduced the AUC by 0.1 to 0.2. CONCLUSIONS: DCNNs may be a useful tool for detecting glaucoma or glaucoma-suspected eyes by use of fundus color images. Proper preprocessing and collection of qualified images are essential to improving the discriminative ability.