In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. ...Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.
In South Korea, a November 2021 outbreak caused by severe acute respiratory syndrome coronavirus 2 Omicron variant originated from 1 person with an imported case and spread to households, ...kindergartens, workplaces, restaurants, and hospitals, resulting in 11 clusters within 3 weeks. An epidemiologic curve indicated rapid community transmission of the Omicron variant.
As the coronavirus disease 2019 (COVID‐19) pandemic continues, reinfection is likely to become increasingly common. However, confirming COVID‐19 reinfection is difficult because it requires ...whole‐genome sequencing of both infections to identify the degrees of genetic differences. Since the first reported case of reinfection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in the Republic of Korea in April 2020, four additional cases were classified as suspected reinfection cases. We performed whole‐genome sequencing of viral RNA extracted from swabs obtained at the initial infection and reinfection stages of these four suspected cases. The interval between initial infection and reinfection of all four suspected cases was more than 3 months. All four patients were young (10–29 years), and they displayed mild symptoms or were asymptomatic during the initial infection and reinfection episodes. The analysis of genome sequences combined with the epidemiological results revealed that only two of the four cases were confirmed as reinfection, and both were reinfected with the Epsilon variant. Due to the prolonged COVID‐19 pandemic, the possibility of reinfections with SARS‐CoV‐2 variants is increasing, as reported in our study. Therefore, continuous monitoring of cases is necessary.
Highlights
We investigated four suspected SARS‐CoV‐2 reinfection cases in Korea.
We performed whole genome sequencing of initial and reinfection samples.
Two of the four suspected cases were confirmed as reinfection cases.
The Epsilon variant was detected in the reinfected patients.
Objective
Increased protein phosphatase magnesium‐dependent 1A (PPM1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential ...mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclear. This study was undertaken to investigate the relationship of PPM1A to osteoclast differentiation by generating conditional gene‐knockout (PPM1Afl/fl;LysM‐Cre) mice and evaluating their bone phenotype.
Methods
The bone phenotypes of LysM‐Cre mice (n = 6) and PPM1Afl/fl;LysM‐Cre mice (n = 6) were assessed by micro–computed tomography. Osteoclast differentiation was induced by culturing bone marrow–derived macrophages in the presence of RANKL and macrophage colony‐stimulating factor (M‐CSF), and was evaluated by counting tartrate‐resistant acid phosphatase–positive multinucleated cells. Levels of messenger RNA for PPM1A, RANK, and osteoclast‐specific genes were examined by real‐time quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Surface RANK expression was analyzed by fluorescence flow cytometry.
Results
The PPM1Afl/fl;LysM‐Cre mice displayed reduced bone mass (P < 0.001) and increased osteoclast differentiation (P < 0.001) and osteoclast‐specific gene expression (P < 0.05) compared with their LysM‐Cre littermates. Mechanistically, reduced PPM1A function in osteoclast precursors in PPM1Afl/fl;LysM‐Cre mice induced osteoclast lineage commitment by up‐regulating RANK expression (P < 0.01) via p38 MAPK activation in response to M‐CSF. PPM1A expression in macrophages was decreased by Toll‐like receptor 4 activation (P < 0.05). The Ankylosing Spondylitis Disease Activity Score was negatively correlated with the expression of PPM1A in peripheral blood mononuclear cells from patients with axial spondyloarthritis (SpA) (γ = −0.7072, P < 0.0001).
Conclusion
The loss of PPM1A function in osteoclast precursors driven by inflammatory signals contributes to osteoclast lineage commitment and differentiation by elevating RANK expression, reflecting a potential role of PPM1A in dynamic bone metabolism in axial SpA.
Information theory provides an interdisciplinary method to understand important phenomena in many research fields ranging from astrophysical and laboratory fluids/plasmas to biological systems. In ...particular, information geometric theory enables us to envision the evolution of non-equilibrium processes in terms of a (dimensionless) distance by quantifying how information unfolds over time as a probability density function (PDF) evolves in time. Here, we discuss some recent developments in information geometric theory focusing on time-dependent dynamic aspects of non-equilibrium processes (e.g., time-varying mean value, time-varying variance, or temperature, etc.) and their thermodynamic and physical/biological implications. We compare different distances between two given PDFs and highlight the importance of a path-dependent distance for a time-dependent PDF. We then discuss the role of the information rate Γ=dLdt and relative entropy in non-equilibrium thermodynamic relations (entropy production rate, heat flux, dissipated work, non-equilibrium free energy, etc.), and various inequalities among them. Here, L is the information length representing the total number of statistically distinguishable states a PDF evolves through over time. We explore the implications of a geodesic solution in information geometry for self-organization and control.
Background
After the detection of the first case of coronavirus disease 2019 (COVID‐19) in South Korea on January 20, 2019, it has triggered three major outbreaks. To decrease the disease burden of ...COVID‐19, social distancing and active mask wearing were encouraged, reducing the number of patients with influenza‐like illness and altering the detection rate of influenza and respiratory viruses in the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS). We examined the changes in respiratory viruses due to COVID‐19 in South Korea and virological causes of the high detection rate of human rhinovirus (hRV) in 2020.
Methods
We collected 52 684 oropharyngeal or nasopharyngeal swab samples from patients with influenza‐like illness in cooperation with KINRESS from 2016 to 2020. Influenza virus and other respiratory viruses were confirmed using real‐time RT‐PCR. The weekly detection rate was used to compare virus detection patterns.
Results
Non‐enveloped virus (hRV, human bocavirus, and human adenovirus) detection rates during the COVID‐19 pandemic were maintained. The detection rate of hRV significantly increased in 2020 compared with that in 2019 and was negatively correlated with number of COVID‐19‐confirmed cases in 2020. The distribution of strains and genetic characteristics in hRV did not differ between 2019 and 2020.
Conclusions
The COVID‐19 pandemic impacted the respiratory virus detection rate. The extremely low detection rate of enveloped viruses resulted from efforts to prevent the spread of COVID‐19 in South Korea. The high detection rate of hRV may be related to resistance against environmental conditions as a non‐enveloped virus and the long period of viral shedding from patients.
The recent discovery of diffuse dwarf galaxies that are deficient in dark matter appears to challenge the current paradigm of structure formation in our universe. We describe numerical experiments to ...determine if so-called dark matter deficient galaxies (DMDGs) could be produced when two gas-rich, dwarf-sized galaxies collide with a high relative velocity of ∼300 km s−1. Using idealized high-resolution simulations with both mesh-based and particle-based gravito-hydrodynamics codes, we find that DMDGs can form as high-velocity galaxy collisions and separate dark matter from the warm disk gas, which subsequently is compressed by shock and tidal interaction to form stars. Then using the large simulated universe IllustrisTNG, we discover a number of high-velocity galaxy collision events in which DMDGs are expected to form. However, we did not find evidence that these types of collisions actually produced DMDGs in the TNG100-1 run. We argue that the resolution of the numerical experiment is critical to realizing the "collision-induced" DMDG formation scenario. Our results demonstrate one of many routes in which galaxies could form with unconventional dark matter fractions.
The continuous emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike (S) protein mutations pose serious threats to current coronavirus disease ...2019 (COVID-19) therapies. A comprehensive understanding of the structural stability of SARS-CoV-2 variants is vital for the development of effective therapeutic strategies as it can offer valuable insights into their potential impact on viral infectivity. S protein mediates a virus’ attachment to host cells by binding to angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD), and mutations in this protein can affect its stability and binding affinity. We analyzed S protein structural stability in various Omicron subvariants computationally. Notably, the S protein sequences analyzed in this work were obtained directly from our own sample collection. We evaluated the binding free energy between S protein and ACE2 in several complex forms. Additionally, we measured distances between the RBD of each chain in S protein to analyze conformational changes. Unlike most of the prior studies, we analyzed full-length S protein–ACE2 complexes instead of only RBD–ACE2 complexes. Omicron subvariants including BA.1, BA.2, BA.2.12.1, BA.4/BA.5, BA.2.75, BA.2.75_K147E, BA.4.6 and BA.4.6_N658S showed enhanced stability compared to wild type, potentially due to distinct S protein mutations. Among them, BA.2.75 and BA.4.6_N658S exhibited the highest and lowest level of stability, respectively.
ObjectiveWe explored clinical implications of the new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) by assessing its prevalence and associated cardiovascular disease ...(CVD) risk.DesignFrom nationwide health screening data, we identified 9 775 066 adults aged 20–79 who underwent health examination in 2009. Participants were categorised into four mutually exclusive groups: (1) MASLD; (2) MASLD with increased alcohol intake (MetALD); (3) MASLD with other combined aetiology (the three collectively referred to as MASLD/related steatotic liver disease (SLD)); and (4) no MASLD/related SLD. SLD was determined by fatty liver index ≥30. The primary outcome was CVD event, defined as a composite of myocardial infarction, ischaemic stroke, heart failure or cardiovascular death.ResultsThe prevalence of MASLD, MetALD and MASLD with other combined aetiology was 27.5%, 4.4% and 1.5%, respectively. A total of 8 808 494 participants without prior CVD were followed up for a median of 12.3 years, during which 272 863 CVD events occurred. The cumulative incidence and multivariable-adjusted risk of CVD were higher in participants with MASLD/related SLD than in those without (HR 1.38 (95% CI 1.37 to 1.39)). Multivariable-adjusted HR (95% CI) of CVD events was 1.39 (1.38 to 1.40) for MASLD, 1.28 (1.26 to 1.30) for MetALD and 1.30 (1.26 to 1.34) for MASLD with other combined aetiology compared to the absence of any of these conditions. CVD risk was also higher in participants with metabolic dysfunction-associated fatty liver disease or non-alcoholic fatty liver disease than in those without the respective condition.ConclusionOver one-third of Korean adults have MASLD/related SLD and bear a high CVD risk.
Cell‐laden structures are widely applied for a variety of tissue engineering applications, including tissue restoration. Cell‐to‐cell interactions in bioprinted structures are important for ...successful tissue restoration, because cell–cell signaling pathways can regulate tissue development and stem cell fate. However, the low degree of cell–cell interaction in conventional cell‐laden bioprinted structures is challenging for the therapeutic application of this modality. Herein, a microfluidic device with cell‐laden methacrylated gelatin (GelMa) bioink and alginate as a matrix hydrogel is used to fabricate a functional hybrid structure laden with cell‐aggregated microbeads. This approach effectively increases the degree of cell‐to‐cell interaction to a level comparable to cell spheroids. The hybrid structure is obtained using a one‐step process without the exhausting procedure. It consists of cell bead fabrication and an extrusion process for the cell‐bead laden structure. Different flow rates are appropriately selected to develop cell‐laden struts with homogeneously distributed cell beads for each hydrogel in the process. The hybrid struts exhibit significantly higher cellular activities than those of conventional alginate/GelMa struts, which are bioprinted using similar cell densities and bioink formulations. Furthermore, hybrid struts with adipose stem cells are implanted into mice, resulting in significantly higher myogenesis in comparison to normally bioprinted struts.
A microfluidic device with cell‐laden methacrylated gelatin bioink and alginate as a matrix hydrogel is used to fabricate a functional hybrid structure laden with cell‐aggregated microbeads. The hybrid structure with adipose stem cells results in significantly higher myogenesis in comparison to normally bioprinted struts.
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