Comparative Interrupted Time Series Analysis of Medical Expenses in Patients with Intertrochanteric Fracture Who Underwent Internal Fixation and Hemiarthroplasty.

Purpose: The objective of this study was to assess postoperative direct medical expenses and medical utilization of elderly patients who underwent either hemiarthroplasty (HA) or internal fixation (IF) for treatment of a femoral intertrochanteric fracture and to analyze differences according to surgical methods and age groups. Materials and Methods: Data from the 2011 to 2018 Korean National Health Insurance Review & Assessment Service database were used. Risk-set matching was performed for selection of controls representing patients with the same sex, age, and year of surgery. A comparative interrupted time series analysis was performed for evaluation of differences in medical expenses and utilization between the two groups. Results: A total of 10,405 patients who underwent IF surgery and 10,405 control patients who underwent HA surgery were included. Medical expenses were 18% lower in the IF group compared to the HA group during the first year after the fracture (difference-in-difference [DID] estimate ratio 0.82, 95% confidence interval [CI] 0.77-0.87, P<0.001), and 9% lower in the second year (DID estimate ratio 0.91, 95% CI 0.85-0.99, P=0.018). Length of hospital stay was significantly shorter in the IF group compared to the HA group during the first two years after time zero in the age ≥80 group. Conclusion: A noticeable increase in medical expenses was observed for patients who underwent HA for treatment of intertrochanteric fractures compared to those who underwent IF over a two-year period after surgery. Therefore, consideration of such findings is critical when designing healthcare policy support for management of intertrochanteric fractures.

One-year mortality and morbidities of severe fever with thrombocytopenia syndrome compared with other diseases: A nationwide cohort study in South Korea.

BACKGROUND: The long-term mortality and morbidity of patients with severe fever with thrombocytopenia syndrome (SFTS) remain unclear. METHODS: This retrospective cohort study was conducted using the National Health Insurance Service dataset on hospitalized patients with SFTS aged ≥20 years between 2016 and 2021 (n = 1,217). Each SFTS case was matched with three controls hospitalized for non-SFTS-related diseases using propensity score matching. The all-cause mortality of patients with SFTS was evaluated during the one-year follow-up and compared with that of controls. Post-discharge events were investigated to determine the effects of SFTS on post-acute sequelae. RESULTS: Finally, 1,105 patients with SFTS and 3,315 controls were included. Patients with SFTS had a higher risk of death during the one-year follow-up than that of controls (hazard ratio [HR], 2·26; 95% confidence interval [CI], 1·82-2·81). Thirty-day mortality was significantly higher in the SFTS group (HR, 3·99; 95% CI, 3·07-5·19) than in the control group. An increased risk of death after 31-365 days was observed among controls, though this difference was significant only among patients in their 80s (HR, 0·18; 95% CI, 0·06-0·57). For post-discharge events, patients in the SFTS group exhibited a higher risk of readmission (HR, 1·17; 95% CI, 1·04-1·32) and emergency room visit (HR, 2·32; 95% CI, 1·96-2·76) than those in the control group. CONCLUSION: SFTS induces a higher risk of short-term mortality and post-acute sequelae in hospitalized patients during a one-year follow-up than non-SFTS-related diseases. Our results provide guidance for the management of SFTS.

Uncovering COVID-19 transmission tree: identifying traced and untraced infections in an infection network.

Introduction: This paper presents a comprehensive analysis of COVID-19 transmission dynamics using an infection network derived from epidemiological data in South Korea, covering the period from January 3, 2020, to July 11, 2021. The network illustrates infector-infectee relationships and provides invaluable insights for managing and mitigating the spread of the disease. However, significant missing data hinder conventional analysis of such networks from epidemiological surveillance. Methods: To address this challenge, this article suggests a novel approach for categorizing individuals into four distinct groups, based on the classification of their infector or infectee status as either traced or untraced cases among all confirmed cases. The study analyzes the changes in the infection networks among untraced and traced cases across five distinct periods. Results: The four types of cases emphasize the impact of various factors, such as the implementation of public health strategies and the emergence of novel COVID-19 variants, which contribute to the propagation of COVID-19 transmission. One of the key findings is the identification of notable transmission patterns in specific age groups, particularly in those aged 20-29, 40-69, and 0-9, based on the four type classifications. Furthermore, we develop a novel real-time indicator to assess the potential for infectious disease transmission more effectively. By analyzing the lengths of connected components, this indicator facilitates improved predictions and enables policymakers to proactively respond, thereby helping to mitigate the effects of the pandemic on global communities. Conclusion: This study offers a novel approach to categorizing COVID-19 cases, provides insights into transmission patterns, and introduces a real-time indicator for better assessment and management of the disease transmission, thereby supporting more effective public health interventions.

Modeling of the brain-lung axis using organoids in traumatic brain injury: an updated review.

Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there is no direct lung damage, severe brain injury can enhance sympathetic tones on blood vessels and vascular resistance, resulting in neurogenic pulmonary edema. Conversely, lung damage can worsen brain damage by dysregulating immunity. These findings suggest the importance of brain-lung axis interactions in TBI. However, little research has been conducted on the topic. An advanced disease model using stem cell technology may be an alternative for investigating the brain and lungs simultaneously but separately, as they can be potential candidates for improving the clinical outcomes of TBI.In this review, we describe the importance of brain-lung axis interactions in TBI by focusing on the concepts and reproducibility of brain and lung organoids in vitro. We also summarize recent research using pluripotent stem cell-derived brain organoids and their preclinical applications in various brain disease conditions and explore how they mimic the brain-lung axis. Reviewing the current status and discussing the limitations and potential perspectives in organoid research may offer a better understanding of pathophysiological interactions between the brain and lung after TBI.

Predicting the transmission trends of COVID-19: an interpretable machine learning approach based on daily, death, and imported cases.

COVID-19 is caused by the SARS-CoV-2 virus, which has produced variants and increasing concerns about a potential resurgence since the pandemic outbreak in 2019. Predicting infectious disease outbreaks is crucial for effective prevention and control. This study aims to predict the transmission patterns of COVID-19 using machine learning, such as support vector machine, random forest, and XGBoost, using confirmed cases, death cases, and imported cases, respectively. The study categorizes the transmission trends into the three groups: L0 (decrease), L1 (maintain), and L2 (increase). We develop the risk index function to quantify changes in the transmission trends, which is applied to the classification of machine learning. A high accuracy is achieved when estimating the transmission trends for the confirmed cases (91.5-95.5%), death cases (85.6-91.8%), and imported cases (77.7-89.4%). Notably, the confirmed cases exhibit a higher level of accuracy compared to the data on the deaths and imported cases. L2 predictions outperformed L0 and L1 in all cases. Predicting L2 is important because it can lead to new outbreaks. Thus, this robust L2 prediction is crucial for the timely implementation of control policies for the management of transmission dynamics.

Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Comparing the efficacy of combined versus single immune cell adaptive therapy targeting colorectal cancer.

PURPOSE: Colorectal cancer (CRC) is the most frequent cancer with limited therapeutic achievements. Recently, adoptive cellular immunotherapy has been developed as an antitumor therapy. However, its efficacy has not been tested in CRC. This study investigated the ability of an immune cell cocktail of dendritic cells (DCs), T cells, and natural killer (NK) cells to overcome immunological hurdles and improve the therapeutic efficacy of cell therapy for CRC. METHODS: CRC lysate-pulsed monocyte-derived DCs (Mo-DCs), CRC antigen-specifically expanded T cells (CTL), and in vitro-expanded NK cells were cultured from patient peripheral blood mononuclear cells (PBMC). The ability of the combined immune cells to kill autologous tumor cells was investigated by co-culturing the combined immune cells with patient-derived tumor cells. RESULTS: The Mo-DCs produced expressed T cell co-stimulating molecules like CD80, CD86, human leukocyte antigen (HLA)-DR and HLA-ABC, at high levels and were capable of activating naive T cells. The expanded T cells were predominantly CD8 T cells with high levels of CD8 effector memory cells and low levels of regulatory T cells. The NK cells expressed high levels of activating receptors and were capable of killing other cancer cell lines (K562 and HT29). The immune cell cocktail demonstrated a higher ability to kill autologous tumor cells than single types. An in vivo preclinical study confirmed the safety of the combined immune cell adaptive therapy showing no therapy-related death or general toxicity symptoms. CONCLUSION: The results suggested that combined immune cell adaptive therapy could overcome the limited efficacy of cell immunotherapy.

Comparison of the performance of MiSeq and NovaSeq in oral microbiome study.

Objective: Next generation sequencing is commonly used to characterize the microbiome structure. MiSeq is most commonly used to analyze the microbiome due to its relatively long read length. Illumina also introduced the 250 × 2 chip for NovaSeq. The purpose of this study was to compare the performance of MiSeq and NovaSeq in the context of oral microbiome study. Methods: Total read count, read quality score, relative bacterial abundance, community diversity, and correlation between two platforms were analyzed. Phylogenetic trees were analyzed for Streptococcus and periodontopathogens. Results: NovaSeq produced significantly more read counts and assigned more operational taxonomic units (OTUs) compared to MiSeq. Community diversity was similar between MiSeq and NovaSeq. NovaSeq were able to detect more unique OTUs compared to MiSeq. When phylogenetic trees were constructed for Streptococcus and periodontopathogens, both platforms detected OTUs for most of the clades. Conclusion: Taken together, while both MiSeq and NovaSeq platforms effectively characterize the oral microbiome, NovaSeq outperformed MiSeq in terms of read counts and detection of unique OTUs, highlighting its potential as a valuable tool for large scale oral microbiome studies.

Comparative Interrupted Time Series Analysis of Direct Medical Expense and Length of Stay in Elderly Patients with Femoral Neck Fractures Who Underwent Total Hip Arthroplasty and Hemiarthroplasty: A Real World Nationwide Database Study.

Background: The objective of our study was to analyze the postoperative direct medical expenses and hospital lengths of stay (LOS) of elderly patients who had undergone either hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fractures and to determine the indication of THA by comparing those variables between the 2 groups by time. Methods: In this comparative large-sample cohort study, we analyzed data from the 2011 to 2018 Korean National Health Insurance Review and Assessment Service database. The included patients were defined as elderly individuals aged 60 years or older who underwent HA or THA for a femoral neck fracture. A 1:1 risk-set matching was performed on the propensity score, using a nearest-neighbor matching algorithm with a maximum caliper of 0.01 of the hazard components. In comparative interrupted time series analysis, time series were constructed using the time unit of one-quarter before and after 3 years from time zero. For the segmented regression analysis, we utilized a generalized linear model with a gamma distribution and logarithmic link function. Results: A total of 4,246 patients who received THA were matched and included with 4,246 control patients who underwent HA. Although there was no statistically significant difference in direct medical expense and hospital LOS for the first 6 months after surgery, direct medical expenses and hospital LOS in THA were relatively reduced compared to the HA up to 24 months after surgery (p < 0.05). In the subgroup analysis, the THA group's hospital LOS decreased significantly compared to that of the HA group during the 7 to 36 months postoperative period in the 65 ≤ age < 80 age group (p < 0.05). Direct medical expenses of the THA group significantly decreased compared to those of the HA group during the period from 7 to 24 months after surgery in the men group (p < 0.05). Conclusions: When performing THA in elderly patients with femoral neck fractures, the possibility of survival for at least 2 years should be considered from the perspective of medical expense and medical utilization. Additionally, in healthy and active male femoral neck fracture patients under the age of 80 years, THA may be more recommended than HA.

Corrigendum: Detection of COVID-19 epidemic outbreak using machine learning.

[This corrects the article DOI: 10.3389/fpubh.2023.1252357.].

Assessing the role of cold front passage and synoptic patterns on air pollution in the Korean Peninsula.

Various numerical experiments using WRF (Weather Research & Forecasting Model) and CMAQ (Community Multiscale Air Quality Modeling System) were performed to analyze the phenomenon of rapidly high concentration PM2.5 after the passage of a cold front in an area with limited local emissions. The episode period was from January 14 to 23, 2018, and analysis was conducted by dividing it into two stages according to the characteristics of changes in PM2.5 concentrations during the period. Through the analysis of observational data during the episode period, we confirmed meteorological impacts (decrease in temperature, increase in wind speed and relative humidity) and an increase in air pollution (PM10 and PM2.5) attributed to the passage of a cold front. Using CMAQ's IPR (Integrated Process Rate) analysis, the contribution of the horizontal advection process was observed in transporting PM2.5 to Gangneung at higher altitudes, and the PM2.5 concentrations at the surface increased because the vertical advection process was influenced by the terrain. Notably, in Stage 2 (64 µg·m-3), a higher contribution of the vertical advection process compared to Stage 1 (35 µg·m-3) was observed, which is attributed to the differences in synoptic patterns following the passage of the cold front. During Stage 2, following the cold front, atmospheric stability (dominance of high-pressure system) led to air subsidence and the presence of a temperature inversion layer, creating favorable meteorological conditions for the accumulation of air pollutants. This study offers the mechanisms of air pollution over the Korean Peninsula under non-stationary meteorological conditions, particularly in relation to the passage of the cold front (low-pressure system). Notably, the influence of a cold front can vary according to the synoptic patterns that develop following its passage.

Exploring miRNA­target gene profiles associated with drug resistance in patients with breast cancer receiving neoadjuvant chemotherapy.

Exosomal microRNAs (miRNAs) are closely related to drug resistance in patients with breast cancer (BC); however, only a few roles of the exosomal miRNA-target gene networks have been clinically implicated in drug resistance in BC. Therefore, the present study aimed to identify the differential expression of exosomal miRNAs associated with drug resistance and their target mRNAs. In vitro microarray analysis was used to verify differentially expressed miRNAs (DEMs) in drug-resistant BC. Next, tumor-derived exosomes (TDEs) were isolated. Furthermore, it was determined whether the candidate drug-resistant miRNAs were also significant in TDEs, and then putative miRNAs in TDEs were validated in plasma samples from 35 patients with BC (20 patients with BC showing no response and 15 patients with BC showing a complete response). It was confirmed that the combination of five exosomal miRNAs, including miR-125b-5p, miR-146a-5p, miR-484, miR-1246-5p and miR-1260b, was effective for predicting therapeutic response to neoadjuvant chemotherapy, with an area under the curve value of 0.95, sensitivity of 75%, and specificity of 95%. Public datasets were analyzed to identify differentially expressed genes (DEGs) related to drug resistance and it was revealed that BAK1, NOVA1, PTGER4, RTKN2, AGO1, CAP1, and ETS1 were the target genes of exosomal miRNAs. Networks between DEMs and DEGs were highly correlated with mitosis, metabolism, drug transport, and immune responses. Consequently, these targets could be used as predictive markers and therapeutic targets for clinical applications to enhance treatment outcomes for patients with BC.

Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers.

Although Astragalus membranaceus is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of Astragalus membranaceus extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of Astragalus membranaceus (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased cytotoxicity and the sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase 3), and attenuated the expression of B-cell lymphoma 2 (Bcl-2) in LNCaP cells after 24 h of exposure. Consistently, WAM significantly increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive LNCaP cells. WAM decreased the phosphorylation of HSP27 on Ser82 and inhibited the expression of the AR and prostate-specific antigen (PSA), along with reducing the nuclear translocation of p-HSP27 and the AR via the disturbed binding of p-HSP27 with the AR in LNCaP cells. WAM consistently inhibited the expression of the AR and PSA in dihydrotestosterone (DHT)-treated LNCaP cells. WAM also suppressed AR stability, both in the presence and absence of cycloheximide, in LNCaP cells. Taken together, these findings provide evidence that WAM induces apoptosis via the inhibition of HSP27/AR signaling in prostate cancer cells and is a potent anticancer candidate for prostate cancer treatment.

Drug-resistant profiles of extracellular vesicles predict therapeutic response in TNBC patients receiving neoadjuvant chemotherapy.

BACKGROUND: Predicting tumor responses to neoadjuvant chemotherapy (NAC) is critical for evaluating prognosis and designing treatment strategies for patients with breast cancer; however, there are no reliable biomarkers that can effectively assess tumor responses. Therefore, we aimed to evaluate the clinical feasibility of using extracellular vesicles (EVs) to predict tumor response after NAC. METHODS: Drug-resistant triple-negative breast cancer (TNBC) cell lines were successfully established, which developed specific morphologies and rapidly growing features. To detect resistance to chemotherapeutic drugs, EVs were isolated from cultured cells and plasma samples collected post-NAC from 36 patients with breast cancer. RESULTS: Among the differentially expressed gene profiles between parental and drug-resistant cell lines, drug efflux transporters such as MDR1, MRP1, and BCRP were highly expressed in resistant cell lines. Drug efflux transporters have been identified not only in cell lines but also in EVs released from parental cells using immunoaffinity-based EV isolation. The expression of drug resistance markers in EVs was relatively high in patients with residual disease compared to those with a pathological complete response. CONCLUSIONS: The optimal combination of drug-resistant EV markers was significantly efficient in predicting resistance to NAC with 81.82% sensitivity and 92.86% specificity.

No increased risk of osteonecrosis of the jaw in osteoporotic patients with dental implants: a nationwide cohort study.

OBJECTIVES: The occurrence of implant-associated osteonecrosis of the jaw (ONJ) has been reported in osteoporotic patients, particularly in association with bisphosphonate therapy. This study aimed to investigate the risk of implant surgery and implant presence for ONJ occurrence in osteoporotic patients longitudinally. METHODS: Based on Korean National Health Information Database, subjects over the age of 65 who were diagnosed with osteoporosis between July 2014 and December 2016 were included. The implant group included subjects who had undergone dental implant surgery between January 2017 and December 2017, while the control group included those who had no history of dental implants. The primary outcome was the occurrence of ONJ, and the date of final follow-up was December 2020. RESULTS: A total of 332,728 subjects with osteoporosis were included in the analysis: 83,182 in the implant group and 249,546 in the control group. The risk of ONJ among those who had undergone implant surgery (risk of implant surgery-associated ONJ) was not higher than that among those without implant surgery. The risk of ONJ among those with implants (risk of implant presence-associated ONJ) was lower than that among those without implants. Even in subjects with a history of bisphosphonates, steroids, periodontitis, or tooth extraction, those who had undergone implant surgery or had implants did not have a higher ONJ risk than those who had not undergone surgery or did not have implants; rather, they showed a lower risk. CONCLUSIONS: The results may suggest that dental implants are not associated with an increased risk of ONJ. A further study on whether dental implants are associated with lower ONJ risk is needed. CLINICAL RELEVANCE: Dental implants did not increase the risk of ONJ development in osteoporotic patients, even with a history of bisphosphonates. This may suggest that the risk profiles for ONJ occurrence between selective insertion of dental implants and other dentoalveolar surgery associated with infectious conditions are different.

Association between toothbrushing and cardiovascular risk factors: a cross-sectional study using Korean National Health and Nutrition Examination Survey 2015-2017.

BACKGROUND: Previous studies have suggested that frequent toothbrushing is associated with a lower risk of future cardiovascular events. We sought to investigate further the relationship between toothbrushing, cardiovascular risk factors, and lifestyle behaviours. METHODS: We analysed a cross-sectional survey including 13,761 adults aged 30 years or older without a history of cardiovascular diseases from the Korean National Health and Nutritional Examination Survey. Conventional cardiovascular risk factors (blood pressure, lipid profiles, and fasting glucose), and inflammatory markers (high-sensitivity C-reactive protein [hsCRP], and white blood cell counts [WBC]) were investigated in relation to the frequency of toothbrushing. RESULTS: The estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort equations was 13.7%, 9.1%, and 7.3% for participants who reported toothbrushing 0-1, 2, and ≥ 3 times a day, respectively. Both conventional risk factors and inflammatory markers were significantly associated with frequent toothbrushing. However, after adjusting potential confounding factors such as age, sex, comorbidities, and lifestyle behaviours, only inflammatory markers were remained as significant factors. CONCLUSIONS: Oral hygiene behaviours are closely linked to cardiovascular risk factors. This study suggests that reduced systemic inflammatory burden may explain the benefit of improved oral hygiene in terms of cardiovascular risk.

Inhibition of glycolysis and SIRT1/GLUT1 signaling ameliorates the apoptotic effect of Leptosidin in prostate cancer cells.

Since the silent information regulation 2 homolog-1 (sirtuin, SIRT1) and glucose transporter 1 (GLUT1) are known to modulate cancer cell metabolism and proliferation, the role of SIRT1/GLUT1 signaling was investigated in the apoptotic effect of Leptosidin from Coreopsis grandiflora in DU145 and PC3 human prostate cancer (PCa) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis, Western blotting, cBioportal correlation analysis, and co-immunoprecipitation were used in this work. Leptosidin showed cytotoxicity, augmented sub-G1 population, and abrogated the expression of pro-poly (ADP-ribose) polymerase (pro-PARP) and pro-cysteine aspartyl-specific protease (pro-caspase3) in DU145 and PC3 cells. Also, Leptosidin inhibited the expression of SIRT1, GLUT1, pyruvate kinase isozymes M2 (PKM2), Hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA) in DU145 and PC3 cells along with disrupted binding of SIRT1 and GLUT1. Consistently, Leptosidin curtailed lactate, glucose, and ATP in DU145 and PC3 cells. Furthermore, SIRT1 depletion enhanced the decrease of GLUT1, LDHA, and pro-Cas3 by Leptosidin in treated DU145 cells, while pyruvate suppressed the ability of Leptosidin in DU145 cells. These findings suggest that Leptosidin induces apoptosis via inhibition of glycolysis and SIRT1/GLUT1 signaling axis in PCa cells.

Reconstruction and analysis of the transmission network of African swine fever in People's Republic of China, August 2018-September 2019.

Introduction of African swine fever (ASF) to China in mid-2018 and the subsequent transboundary spread across Asia devastated regional swine production, affecting live pig and pork product-related markets worldwide. To explore the spatiotemporal spread of ASF in China, we reconstructed possible ASF transmission networks using nearest neighbour, exponential function, equal probability, and spatiotemporal case-distribution algorithms. From these networks, we estimated the reproduction numbers, serial intervals, and transmission distances of the outbreak. The mean serial interval between paired units was around 29 days for all algorithms, while the mean transmission distance ranged 332 -456 km. The reproduction numbers for each algorithm peaked during the first two weeks and steadily declined through the end of 2018 before hovering around the epidemic threshold value of 1 with sporadic increases during 2019. These results suggest that 1) swine husbandry practices and production systems that lend themselves to long-range transmission drove ASF spread; 2) outbreaks went undetected by the surveillance system. Efforts by China and other affected countries to control ASF within their jurisdictions may be aided by the reconstructed spatiotemporal model. Continued support for strict implementation of biosecurity standards and improvements to ASF surveillance is essential for halting transmission in China and spread across Asia.

A longitudinal molecular and cellular lung atlas of lethal SARS-CoV-2 infection in K18-hACE2 transgenic mice.

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 TGFß 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 TGFß 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).