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Summary: Background: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus’s impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research. Methods: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue. Findings: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor–ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFβ signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes. Interpretation: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFβ signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19. Funding: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020M3A9I2109027, 2021R1A2C2004501).

Abstract Background As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Abstract Background Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic. Methods We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern. Results A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses. Conclusion One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.

Background/Objectives: Patients with chronic rhinosinusitis (CRS) accompanied by asthma often show poor prognoses and require continuous management. This study aimed to assess the prognostic value of eosinophil counts in nasal polyp tissue for selecting individuals who would benefit from ongoing management in CRS patients with asthma. Methods: Patients with asthma who underwent endoscopic sinus surgery for CRS with nasal polyps were included in the study. Eosinophil counts in nasal polyp tissues were quantified, and retrospective data were collected from laboratory and clinical findings, including endoscopic examinations, CT scans, and Japan Endoscopic Sinus Surgery Rating and Evaluation Committee (JESREC) scores. Disease control status was evaluated through endoscopic examination 6 months post-surgery. Results: A total of 42 patients were divided into two groups based on their disease management status 6 months post-operation: the well-control group (24 patients, 57.14%) and the poor-control group (18 patients, 42.86%). Demographics and laboratory findings did not show significant differences between the groups. However, the JESREC score (p = 0.04) and tissue eosinophil count (p = 0.02) were significantly different. Multivariate analysis identified tissue eosinophil count as the only risk factor associated with prognosis, with a cut-off value of 90/HPF. Conclusions: In CRS patients with asthma, high tissue eosinophil counts in nasal polyps were associated with poor disease control, which is the most potent predictor of prognosis. The assessment of eosinophil counts in nasal polyp tissue could aid in identifying patients who would benefit from continuous management and tailored interventions for improved outcomes. [ABSTRACT FROM AUTHOR]

In this study, a multivariate piecewise interpolation model is introduced to represent melt viscosity based on temperature and shear rate. The model does not require a predefined functional form for the entire data range, instead finding a suitable line between adjacent measured viscosity data points to obtain viscosity as a function of shear rate and temperature. To assess the effect of viscosity representation on polymer melt flow, a two-dimensional (2D) flow past a cylinder problem and a three-dimensional (3D) single screw extruder problem are numerically solved using different viscosity models. The pressure drop (Δ P) from the shift-factor model deviates by more than 10% at an average velocity ( U av ) of 1 m/s due to overestimation of viscosity in the high shear rate region. The dimensionless thicknesses of the thermal boundary layer near the channel wall ( δ T / H ) at wall temperature ( T w ) of 210 °C are also misevaluated by more than 4% using both the shift-factor model and the Klein model, reflecting their poor viscosity evaluation. It is noteworthy that in all viscosity models, a high T w leads to the formation of a thin thermal boundary layer, which adversely affects the heat transfer. In single screw extruder applications, viscosity misevaluation in high shear rate regions causes issues in pure drag flow cases, while misevaluation in low shear rate regions causes issues in pure back-pressure flow cases. These analyses highlight the accuracy and versatility of our multivariate piecewise interpolation model compared to existing viscosity models. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.

Human papillomavirus (HPV)–related multiphenotypic sinonasal carcinoma (HMSC) is a recently described neoplasm entity that presents only in the sinonasal tract. Histologically, it displays features of both a surface-derived carcinoma and a salivary gland carcinoma, and is associated with high-risk HPV, specifically HPV type 33. Whereas majority of the cases display high-grade histologic features, HMSC paradoxically behaves in a relatively indolent fashion. It is important and meaningful to distinguish HMSC from other histopathologic mimickers as the clinical features and management are distinctive. A 64-year-old woman presented having intermittent left-side epistaxis and progressive nasal obstruction. A well-defined, solitary, friable mass with an irregular surface that easily bled upon contact was found in the posterior part of the left nasal cavity. Endoscopic excision of the tumor which was originated from left nasal septum was done and the tumor was confirmed as HMSC. After surgery, definitive radiotherapy was performed in 28 fractions. HMSC is a histopathological type that has been rarely reported so that we report this case with literature review. [ABSTRACT FROM AUTHOR]

This study numerically explores the influence of thixotropy on flow and mixing in a staggered-herringbone micromixer (SHM), employing a structure-kinetics model to simulate the microstructure formation and breakup in thixotropic fluids. This study represents the first of its kind to incorporate a thixotropic fluid model into microfluidic mixing in channels with patterned grooves. Specifically, we examine the effects of the destruction factor ( k d ) and the thixotropy number (Th) on microstructure, flow, and mixing in the SHM, covering extensive ranges (0.01 ≤ k d ≤ 10 and 0.01 ≤ Th ≤ 100). Higher values of k d and Th , particularly for k d > 1 and Th > 1 , lead to larger spatial variations of the structure parameter (λ) and viscosity (η), with a notable decrease in λ near the groove tops, leading to the lowest viscosity in these areas. Conversely, at the groove bottoms, where shear deformation is minimal, there is less reduction in λ , leading to increased viscosity and higher flow resistance. The viscosity variations inside the grooves impede lateral flows, adversely affecting mixing in the higher k d and Th regimes. Therefore, an in-depth understanding of the complex thixotropic behaviors, as influenced by k d and Th near the grooves, is essential for achieving effective mixing in the SHM when using thixotropic fluids. Our results suggest that lowering the channel height, for a given groove depth, slightly improves the mixing of thixotropic fluids. Further enhanced mixing is achieved by combining a reduced channel height with double-sided groove patterns. [ABSTRACT FROM AUTHOR]

Background and Objective: There is a paucity of literature comparing unilateral instrumented transforaminal lumbar interbody fusion (UITLIF) with bilateral instrumented TLIF (BITLIF) regarding radiological alignment, including the coronal balance, even though UITLIF might have asymmetric characteristics in the coronal plane. This retrospective study aimed to compare the clinical and long-term radiological outcomes of 1-level UITLIF and BITLIF in lumbar degenerative diseases (LDD) including lumbar spinal stenosis with or without spondylolisthesis (degenerative or spondylolytic). Materials and Methods: Patients who underwent 1-level UITLIF with two rectangular polyetheretherketone (PEEK) cages or BITLIF between November 2009 and June 2016 by four surgeons with ≥5 years of follow-up at a single hospital were included. We compared the clinical and radiological outcomes between the UITLIF and BITLIF. Results: In total, 63 and 111 patients who underwent UITLIF and BITLIF, respectively, were enrolled. The median follow-up was 85.55 months (range: 60–130). The UITLIF group had a significantly shorter operation time (185.0 [170.0–210.0] vs. 225.0 [200.0–265.0], p < 0.001) and lower estimated blood loss (300.0 [250.0–500.0] vs. 550.0 [400.0–800.0], p < 0.001) than the BITLIF group. Regarding the clinical outcomes, there were no significant differences in the intermittent claudication score (p = 0.495) and Kirkaldy–Willis criteria (p = 0.707) at 1 year postoperatively. The interval changes in the local coronal Cobb angle at the index level, L1-S1 lordotic angle, and coronal off-balance from the immediate postoperative radiograph to the last follow-up were not significantly different (p = 0.687, p = 0.701, and p = 0.367, respectively). Conclusions: UITLIF with two rectangular PEEK cages may provide comparable clinical outcomes and radiological longevity including coronal alignment to BITLIF in 1-level LDD. In addition, UITLIF has advantages over BITLIF in terms of operative time and blood loss. [ABSTRACT FROM AUTHOR]