Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated ...with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.
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•Critical COVID-19 is associated with enhanced eosinophil-mediated inflammation•FcγR signal and complement activation are elevated in critical COVID-19•Immune complexes and MAC are consistently detected in lung tissues from fatal cases•Th2-biased humoral responses are associated with critical COVID-19
Kim et al. find that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. Increased Th2-biased immune responses, accompanying overt complement activation, are seen in the critical group. These findings suggest that enhanced eosinophil-mediated inflammation and dysregulated humoral responses might be drivers of severe COVID-19.
Mesenchymal stem cell (MSC) is a promising tool for the therapy of immune disorders. However, their efficacy and mechanisms in treating allergic skin disorders are less verified. We sought to ...investigate the therapeutic efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) against murine atopic dermatitis (AD) and to explore distinct mechanisms that regulate their efficacy. AD was induced in mice by the topical application of Dermatophagoides farinae. Naïve or activated-hUCB-MSCs were administered to mice, and clinical severity was determined. The subcutaneous administration of nucleotide-binding oligomerization domain 2 (NOD2)-activated hUCB-MSCs exhibited prominent protective effects against AD, and suppressed the infiltration and degranulation of mast cells (MCs). A β-hexosaminidase assay was performed to evaluate the effect of hUCB-MSCs on MC degranulation. NOD2-activated MSCs reduced the MC degranulation via NOD2-cyclooxygenase-2 signaling. In contrast to bone marrow-derived MSCs, hUCB-MSCs exerted a cell-to-cell contact-independent suppressive effect on MC degranulation through the higher production of prostaglandin E2 (PGE2 ). Additionally, transforming growth factor (TGF)-β1 production from hUCB-MSCs in response to interleukin-4 contributed to the attenuation of MC degranulation by downregulating FcεRI expression in MCs. In conclusion, the subcutaneous application of NOD2-activated hUCB-MSCs can efficiently ameliorate AD, and MSC-derived PGE2 and TGF-β1 are required for the inhibition of MC degranulation.
Motivated by recent experimental efforts on three-dimensional semimetals, we investigate the static and dynamic density response of the nodal line semimetal by computing the polarizability for both ...undoped and doped cases. The nodal line semimetal in the absence of doping is characterized by a ring-shape zero energy contour in momentum space, which may be considered as a collection of Dirac points. In the doped case, the Fermi surface has a torus shape and two independent processes of the momentum transfer contribute to the singular features of the polarizability even though we only have a single Fermi surface. In the static limit, there exist two independent singularities in the second derivative of the static polarizability. This results in the highly anisotropic Friedel oscillations which show the angle-dependent algebraic power law and the beat phenomena in the oscillatory electron density near a charged impurity. Furthermore, the dynamical polarizability has two singular lines along = γ p and = γ p sin , where is the angle between the external momentum p and the plane where the nodal ring lies. From the dynamical polarizability, we obtain the plasmon modes in the doped case, which show anisotropic dispersions and angle-dependent plasma frequencies. Qualitative differences between the low and high doping regimes are discussed in light of future experiments.
Genome-wide association studies (GWAS) have enabled the discovery of candidate markers that play significant roles in various complex traits in plants. Recently, with increased interest in the search ...for candidate markers, studies on epistatic interactions between single nucleotide polymorphism (SNP) markers have also increased, thus enabling the identification of more candidate markers along with GWAS on single-variant-additive-effect. Here, we focused on the identification of candidate markers associated with flowering time in soybean (Glycine max). A large population of 2,662 cultivated soybean accessions was genotyped using the 180k Axiom® SoyaSNP array, and the genomic architecture of these accessions was investigated to confirm the population structure. Then, GWAS was conducted to evaluate the association between SNP markers and flowering time. A total of 93 significant SNP markers were detected within 59 significant genes, including E1 and E3, which are the main determinants of flowering time. Based on the GWAS results, multilocus epistatic interactions were examined between the significant and non-significant SNP markers. Two significant and 16 non-significant SNP markers were discovered as candidate markers affecting flowering time via interactions with each other. These 18 candidate SNP markers mapped to 18 candidate genes including E1 and E3, and the 18 candidate genes were involved in six major flowering pathways. Although further biological validation is needed, our results provide additional information on the existing flowering time markers and present another option to marker-assisted breeding programs for regulating flowering time of soybean.
While colorectal cancer is known to occur in the gastrointestinal tract. It is the third most common form of cancer of 27 major types of cancer in South Korea and worldwide. Colorectal polyps are ...known to increase the potential of developing colorectal cancer. Detected polyps need to be resected to reduce the risk of developing cancer. This research improved the performance of polyp classification through the fine-tuning of Network-in-Network (NIN) after applying a pre-trained model of the ImageNet database. Random shuffling is performed 20 times on 1000 colonoscopy images. Each set of data are divided into 800 images of training data and 200 images of test data. An accuracy evaluation is performed on 200 images of test data in 20 experiments. Three compared methods were constructed from AlexNet by transferring the weights trained by three different state-of-the-art databases. A normal AlexNet based method without transfer learning was also compared. The accuracy of the proposed method was higher in statistical significance than the accuracy of four other state-of-the-art methods, and showed an 18.9% improvement over the normal AlexNet based method. The area under the curve was approximately 0.930 ± 0.020, and the recall rate was 0.929 ± 0.029. An automatic algorithm can assist endoscopists in identifying polyps that are adenomatous by considering a high recall rate and accuracy. This system can enable the timely resection of polyps at an early stage.
Background
Bismuth‐based quadruple therapy (BQT) is recommended as the first‐line empirical therapy for Helicobacter pylori eradication as it is not associated with resistance. However, few studies ...have investigated the use of potassium‐competitive acid blockers for BQT.
Aim
To investigate the efficacy and safety profiles of tegoprazan‐based BQT (TBMT) versus lansoprazole‐based BQT (LBMT) for H. pylori eradication.
Methods
We included patients older than 18 with an H. pylori infection without a history of H. pylori eradication who visited four university‐affiliated hospitals between March 2020 and December 2021. H. pylori infection was diagnosed using a rapid urease test or Giemsa staining. Patients were randomly assigned to the TBMT or LBMT group.
Results
217 subjects were randomly allocated to receive either TBMT (n = 108) or LBMT (n = 109) therapy. Intention‐to‐treat (ITT) eradication rates of TBMT and LBMT were 80.0% and 77.4% (95% confidence interval CI: −8.4 to 13.7, p = 0.0124), respectively. Corresponding modified ITT rates were 90.3% and 84.5% (95% CI: −3.6 to 15.2, p = 0.0005), respectively. Per‐protocol (PP) eradication rates of TBMT and LBMT were 90.2% and 82.4% (95% CI: −2.5 to 18.2, p = 0.0003), respectively. There was no significant difference in the rate of adverse events between the TBMT and LBMT groups (39.1% vs. 43.4%, p = 0.5211). TBMT showed higher eradication rates than that of LBMT in ITT, m‐ITT, and PP analysis.
Conclusion
TBMT showed a noninferior eradication rate and similar adverse events to LBMT as a first‐line eradication regimen. Our results suggest that tegoprazan might be substituted for proton pump inhibitors in H. pylori eradication regimens.
This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on ...confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio OR 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0-4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949-0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.
As a paradigm to recover the sparse signal from a small set of linear measurements, compressed sensing (CS) has stimulated a great deal of interest in recent years. In order to apply the CS ...techniques to wireless communication systems, there are a number of things to know and also several issues to be considered. However, it is not easy to grasp simple and easy answers to the issues raised while carrying out research on CS. The main purpose of this paper is to provide essential knowledge and useful tips and tricks that wireless communication researchers need to know when designing CS-based wireless systems. First, we present an overview of the CS technique, including basic setup, sparse recovery algorithm, and performance guarantee. Then, we describe three distinct subproblems of CS, viz., sparse estimation, support identification, and sparse detection, with various wireless communication applications. We also address main issues encountered in the design of CS-based wireless communication systems. These include potentials and limitations of CS techniques, useful tips that one should be aware of, subtle points that one should pay attention to, and some prior knowledge to achieve better performance. Our hope is that this paper will be a useful guide for wireless communication researchers and even non-experts to get the gist of CS techniques.
The risk of complications of nonsurgical hypoparathyroidism in Asia is unclear. We estimated the prevalence and risk of complications in patients with nonsurgical hypoparathyroidism.
We performed a ...retrospective cohort study using a nationwide claims database from 2005 to 2016. Among the entire Korean population, we identified 897 patients diagnosed with nonsurgical hypoparathyroidism during 2005-2015. We selected 210 patients with nonsurgical hypoparathyroidism during 2005-2008 who had no complications at baseline and followed them to 2016. Control subjects (n = 2075) were matched using propensity scores based on age, sex, and comorbid disease with a 1:10 ratio and monitored until 2016.
The age-standardized prevalence of nonsurgical hypoparathyroidism was 0.2 cases per 100,000 persons in 2005. During a mean follow-up period of 9.5 years, patients with nonsurgical hypoparathyroidism had a higher risk of cardiovascular disease, especially arrhythmia (hazard ratio HR, 2.03; 95% confidence interval CI, 1.11-3.70) and heart failure (HR, 2.43; 95% CI, 1.22-4.83). The risk of vertebral fracture was higher in patients than in controls (HR, 2.27; 95% CI, 1.09-4.72). Patients had a significantly increased risk of renal disease (HR, 2.57; 95% CI, 1.56-4.21), seizure (HR, 5.74; 95% CI, 3.34-9.86), depression and bipolar disease (HR, 1.82; 95% CI, 1.30-2.56), and cataract (HR, 1.90; 95% CI, 1.30-2.79) compared with controls.
The prevalence of nonsurgical hypoparathyroidism was very low in Korea but was associated with a higher risk of incident cardiovascular disease and vertebral fracture as well as known complications including renal disease, seizure, and cataract.
In vivo gene editing in post-mitotic neurons of the adult brain may be a useful strategy for treating neurological diseases. Here, we develop CRISPR-Cas9 nanocomplexes and show they were effective in ...the adult mouse brain, with minimal off-target effects. Using this system to target Bace1 suppressed amyloid beta (Aβ)-associated pathologies and cognitive deficits in two mouse models of Alzheimer's disease. These results broaden the potential application of CRISPR-Cas9 systems to neurodegenerative diseases.
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