Recommendations for Adult Immunization by the Korean Society of Infectious Diseases, 2023: Minor Revisions to the 3rd Edition.

The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect.

Structural Diversification of Pyrazinone Metabolites via Spontaneous Oxa-Michael Addition in Staphylococcus xylosus.

A family of pyrazinone metabolites (1-11) were characterized from Staphylococcus xylosus ATCC 29971. Six of them were hydroxylated or methoxylated, which were proposed to be produced by the rare noncatalytic oxa-Michael addition reaction with a water or methanol molecule. It was confirmed that isopropyl alcohol can also be the Michael donor of the reaction. 1-7 and the synthetic precursor 2a showed significant inhibition of breast cancer cell migration.

Side- and Sinus-Specific Relationships between Chronic Rhinosinusitis and Ischemic Stroke Using Imaging Analyses.

Recent studies have reported chronic rhinosinusitis (CRS) as an independent risk factor for stroke. However, the association with stroke depending on the affected sinuses has not been explored. This study aimed to elucidate the side- and sinus-specific relationship between CRS and ischemic stroke through imaging analyses. We retrospectively reviewed the medical records of patients who were diagnosed with ischemic stroke at a tertiary center. CRS was defined as having a total score of greater than or equal to 4, according to the Lund-Mackay scoring system, through brain magnetic resonance imaging or computed tomography. We investigated the side- and sinus-specific correlation between CRS and ischemic stroke. Subgroup analyses were performed for different age groups. CRS prevalence in patients with ischemic stroke was 18.4%, which was higher than the previously reported prevalence in the general population. Overall, there was no correlation between the directions of the CRS and ischemic stroke (p > 0.05). When each sinus was analyzed, the frontal (Cramer's V = 0.479, p < 0.001), anterior (Cramer's V = 0.396, p < 0.001)/posterior (Cramer's V = 0.300, p = 0.008) ethmoid, and sphenoid (Cramer's V = 0.383, p = 0.005) sinuses showed a statistically significant correlation with the side of stroke, but the maxillary sinus (Cramer's V = 0.138, p = 0.208) did not. In subgroup analyses, a significant right-side correlation between the two diseases was observed in the older-age subgroup (≥65 years old, Cramer's V = 0.142, p = 0.040). Diabetes mellitus (odds ratio = 1.596, 95% confidence interval = 1.204-2.116) was identified as an independent risk factor for having CRS in patients with ischemic stroke. CRS of the frontal, anterior/posterior ethmoid, and sphenoid sinuses has a directional relationship with ischemic stroke. Our results on which sinuses correlate with stroke advocate for the active surveillance of CRS in patients at high risk of ischemic stroke.

In Vitro Biological Activities of Hesperidin-Related Compounds with Different Solubility.

The biological activities of hesperidin-related compounds, such as hesperetin laurate (HTL), hesperetin (HT), hesperidin (HD), and hesperidin glucoside (HDG), were investigated in vitro. The compounds showed different hydrophobicities, and the octanol-water partition coefficient log P were 7.28 ± 0.06 for HTL, 2.59 ± 0.04 for HT, 2.13 ± 0.03 for HD, and -3.45 ± 0.06 for HDG, respectively. In the DPPH assay and ß-carotene bleaching assay to determine antioxidant capacity, all compounds tested showed antioxidant activity in a concentration-dependent manner, although to varying degrees. HTL and HT showed similarly high activities compared to HD or HDG. HD and HDG did not show a significant difference despite the difference in solubility between the two. Cytotoxicity was high; in the order of hydrophobicity-HTL > HT > HD > HDL in keratinocyte HaCaT cells. All compounds tested showed reducing effects on cellular inflammatory mediators and cytokines induced by UV irradiation. However, HTL and HT effectively reduced nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) levels compared to HD and HDG. The inhibitory effects of hesperidin-related compounds on skin-resident microorganisms were evaluated by measuring minimum inhibitory concentration (MIC). HTL showed the highest inhibitory effects against Staphylococcus aureus, Cutibacterium acnes, Candida albicans, and Malassezia furfur, followed by HT, while HD and HDF showed little effect. In conclusion, the hydrophobicity of hesperidin-related compounds was estimated to be important for biological activity in vitro, as was the presence or absence of the sugar moiety.

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.

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.

Effect of apigetrin in pseudo-SARS-CoV-2-induced inflammatory and pulmonary fibrosis in vitro model.

SARS-CoV-2 has become a global public health problem. Acute respiratory distress syndrome (ARDS) is the leading cause of death due to the SARS-CoV-2 infection. Pulmonary fibrosis (PF) is a severe and frequently reported COVID-19 sequela. In this study, an in vitro model of ARDS and PF caused by SARS-CoV-2 was established in MH-S, THP-1, and MRC-5 cells using pseudo-SARS-CoV-2 (PSCV). Expression of proinflammatory cytokines (IL-6, IL-1ß, and TNF-α) and HIF-1α was increased in PSCV-infected MH-S and THP-1 cells, ARDS model, consistent with other profiling data in SARS-CoV-2-infected patients have been reported. Hypoxia-inducible factor-1 alpha (HIF-1α) siRNA and cobalt chloride were tested using this in vitro model. HIF-1α knockdown reduces inflammation caused by PSCV infection in MH-S and THP-1 cells and lowers elevated levels of CTGF, COLA1, and α-SMA in MRC-5 cells exposed to CPMSCV. Furthermore, apigetrin, a glycoside bioactive dietary flavonoid derived from several plants, including Crataegus pinnatifida, which is reported to be a HIF-1α inhibitor, was tested in this in vitro model. Apigetrin significantly reduced the increased inflammatory cytokine (IL-6, IL-1ß, and TNF-α) expression and secretion by PSCV in MH-S and THP-1 cells. Apigetrin inhibited the binding of the SARS-CoV-2 spike protein RBD to the ACE2 protein. An in vitro model of PF induced by SARS-CoV-2 was produced using a conditioned medium of THP-1 and MH-S cells that were PSCV-infected (CMPSCV) into MRC-5 cells. In a PF model, CMPSCV treatment of THP-1 and MH-S cells increased cell growth, migration, and collagen synthesis in MRC-5 cells. In contrast, apigetrin suppressed the increase in cell growth, migration, and collagen synthesis induced by CMPSCV in THP-1 and MH-S MRC-5 cells. Also, compared to control, fibrosis-related proteins (CTGF, COLA1, α-SMA, and HIF-1α) levels were over two-fold higher in CMPSV-treated MRC-5 cells. Apigetrin decreased protein levels in CMPSCV-treated MRC-5 cells. Thus, our data suggest that hypoxia-inducible factor-1 alpha (HIF-1α) might be a novel target for SARS-CoV-2 sequela therapies and apigetrin, representative of HIF-1alpha inhibitor, exerts anti-inflammatory and PF effects in PSCV-treated MH-S, THP-1, and CMPVSC-treated MRC-5 cells. These findings indicate that HIF-1α inhibition and apigetrin would have a potential value in controlling SARS-CoV-2-related diseases.

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.

Microbial diversity, genomics, and phage-host interactions of cyanobacterial harmful algal blooms.

The occurrence of cyanobacterial harmful algal blooms (cyanoHABs) is related to their physical and chemical environment. However, less is known about their associated microbial interactions and processes. In this study, cyanoHABs were analyzed as a microbial ecosystem, using 1 year of 16S rRNA sequencing and 70 metagenomes collected during the bloom season from Lake Okeechobee (Florida, USA). Biogeographical patterns observed in microbial community composition and function reflected ecological zones distinct in their physical and chemical parameters that resulted in bloom "hotspots" near major lake inflows. Changes in relative abundances of taxa within multiple phyla followed increasing bloom severity. Functional pathways that correlated with increasing bloom severity encoded organic nitrogen and phosphorus utilization, storage of nutrients, exchange of genetic material, phage defense, and protection against oxidative stress, suggesting that microbial interactions may promote cyanoHAB resilience. Cyanobacterial communities were highly diverse, with picocyanobacteria ubiquitous and oftentimes most abundant, especially in the absence of blooms. The identification of novel bloom-forming cyanobacteria and genomic comparisons indicated a functionally diverse cyanobacterial community with differences in its capability to store nitrogen using cyanophycin and to defend against phage using CRISPR and restriction-modification systems. Considering blooms in the context of a microbial ecosystem and their interactions in nature, physiologies and interactions supporting the proliferation and stability of cyanoHABs are proposed, including a role for phage infection of picocyanobacteria. This study displayed the power of "-omics" to reveal important biological processes that could support the effective management and prediction of cyanoHABs. IMPORTANCE: Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them.

Very early vs delayed invasive strategy in high-risk NSTEMI patients without hemodynamic instability: Insight from the KAMIR-NIH.

BACKGROUND: High-risk non-ST-elevation myocardial infarction (NSTEMI) patients' optimal timing for percutaneous coronary intervention (PCI) is debated despite the recommendation for early invasive revascularization. This study aimed to compare outcomes of NSTEMI patients without hemodynamic instability undergoing very early invasive strategy (VEIS, ≤ 12 hours) versus delayed invasive strategy (DIS, >12 hours). METHODS: Excluding urgent indications for PCI including initial systolic blood pressure under 90 mmHg, ventricular arrhythmia, or Killip class IV, 4,733 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). Patients were divided into low and high- global registry of acute coronary events risk score risk score (GRS) groups based on 140. Both groups were then categorized into VEIS and DIS. Clinical outcomes, including all-cause death (ACD), cardiac death (CD), recurrent MI, and cerebrovascular accident at 12 months, were evaluated. RESULTS: Among 4,733 NSTEMI patients, 62% had low GRS, and 38% had high GRS. The proportions of VEIS and DIS were 43% vs. 57% in the low GRS group and 47% vs. 53% in the high GRS group. In the low GRS group, VEIS and DIS demonstrated similar outcomes; however, in the high GRS group, VEIS exhibited worse ACD outcomes compared to DIS (HR = 1.46, P = 0.003). The adverse effect of VEIS was consistent with propensity score matched analysis (HR = 1.34, P = 0.042). CONCLUSION: VEIS yielded worse outcomes than DIS in high-risk NSTEMI patients without hemodynamic instability in real-world practice.

3,3',4,4'-tetrachlorobiphenyl (PCB77) enhances human Kv1.3 channel currents and alters cytokine production.

Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat to the environment and human health. The Kv1.3 and Kv1.5 channels have been implicated in the immunotoxicity and cardiotoxicity of PCBs, respectively. We determined whether 3,3',4,4'-tetrachlorobiphenyl (PCB77), a dioxin-like PCB, alters human Kv1.3 and Kv1.5 currents using the Xenopus oocyte expression system. Exposure to 10 nM PCB77 for 15 min enhanced the Kv1.3 current by approximately 30.6%, whereas PCB77 did not affect the Kv1.5 current at concentrations up to 10 nM. This increase in the Kv1.3 current was associated with slower activation and inactivation kinetics as well as right-shifting of the steady-state activation curve. Pretreatment with PCB77 significantly suppressed tumor necrosis factor-α and interleukin-10 production in lipopolysaccharide-stimulated Raw264.7 macrophages. Overall, these data suggest that acute exposure to trace concentrations of PCB77 impairs immune function, possibly by enhancing Kv1.3 currents.

Sleep Characteristics of an International Sample of Adult Gamers.

Introduction About 65% of adult Americans report playing video games. Despite potential impacts to functioning, there is limited research on the relationship between video game use and sleep, specifically among adults. The present study expands upon the literature by describing demographic, video game, and sleep characteristics of an international adult sample of gamers. Methods The participants were 3,481 adults aged 18 to 74 who responded to an online questionnaire about video game use (i.e., quantity of play, most common game type), general sleep characteristics (i.e., sleep onset latency [SOL]; duration, sleep timing, and sleep quality), and gaming-specific sleep disruptors (i.e., game-related night awakenings and sleep delays). Most identified as cisgender male (79.8%) and white (77%). Results Participants reported an average SOL of 24.63 minutes, and most (64.5%) had a sleep duration from 7 to 9 hours with an overall average of 8.42 hours. Most (58.7%) reported that their sleep quality was fair to very poor . Bed and wake times were generally delayed, with 51% reporting a late evening or early morning bedtime and an average wake time of 8:28 am. A majority (81.2%) indicated that their bedtime was delayed due to game-related activities, but game-related night awakenings were less common. Conclusion Although many report a sufficient amount of sleep, adult gamers tend to report sleep disruptions in other domains, particularly regarding a delayed sleep schedule and poor sleep quality. This may be attributable to game-related bedtime delays or other game-specific factors (e.g., game type) that should be evaluated in the future.

Multicolor Two-Photon Microscopy Imaging of Lipid Droplets and Liver Capsule Macrophages In Vivo.

Lipid droplets (LDs) store energy and supply fatty acids and cholesterol. LDs are a hallmark of chronic nonalcoholic fatty liver disease (NAFLD). Recently, studies have focused on the role of hepatic macrophages in NAFLD. Green fluorescent protein (GFP) is used for labeling the characteristic targets in bioimaging analysis. Cx3cr1-GFP mice are widely used in studying the liver macrophages such as the NAFLD model. Here, we have developed a tool for two-photon microscopic observation to study the interactions between LDs labeled with LD2 and liver capsule macrophages labeled with GFP in vivo. LD2, a small-molecule two-photon excitation fluorescent probe for LDs, exhibits deep-red (700 nm) fluorescence upon excitation at 880 nm, high cell staining ability and photostability, and low cytotoxicity. This probe can clearly observe LDs through two-photon microscopy (TPM) and enables the simultaneous imaging of GFP+ liver capsule macrophages (LCMs) in vivo in the liver capsule of Cx3cr1-GFP mice. In the NAFLD mouse model, Cx3cr1+ LCMs and LDs increased with the progress of fatty liver disease, and spatiotemporal changes in LCMs were observed through intravital 3D TPM images. LD2 will aid in studying the interactions and immunological roles of hepatic macrophages and LDs to better understand NAFLD.

Transferrin-conjugated magnetic nanoparticles for the isolation of brain-derived blood exosomal MicroRNAs: A novel approach for Parkinson's disease diagnosis.

BACKGROUND: Brain-derived exosomes circulate in the bloodstream and other bodily fluids, serving as potential indicators of neurological disease progression. These exosomes present a promising avenue for the early and precise diagnosis of neurodegenerative conditions. Notably, miRNAs found in plasma extracellular vesicles (EVs) offer distinct diagnostic benefits due to their stability, abundance, and resistance to breakdown. RESULTS: In this study, we introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction. Our method successfully isolated EVs from 33 human plasma samples, including those from patients with Parkinson's disease (PD), Multiple Sclerosis (MS), and Dementia. Using quantitative polymerase chain reaction (PCR) analysis, we evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates. Six exosomal miRNA biomarkers (miR-195-5p, miR-495-3p, miR-23b-3P, miR-30c-2-3p, miR-323a-3p, and miR-27a-3p) were consistently linked with all stages of PD. SIGNIFICANCE: The TMNs method provides a practical, cost-efficient way to isolate EVs from biological samples, paving the way for non-invasive neurological diagnoses. Furthermore, the identified miRNA biomarkers in these exosomes may emerge as innovative tools for precise diagnosis in neurological disorders including PD.

Factors and age-related drivers that influence self-rated bad health in police officers: A cross-sectional study.

Objective: Although some previous studies have investigated health in police officers, investigations of related factors have been limited to work-related associations or those affecting certain police officers. To address this gap, this study investigated relationships between sociodemographic factors, work-related factors, health behaviors, health conditions, and self-rated bad health (SRBH) in Korean police officers. Methods: In 2021, we conducted a cross-sectional survey in cooperation with the Korean National Police Agency (KNPA). The respondents were 6,591 police officers aged 21-60 years, all of whom agreed to complete the survey online using the police agency's intranet. After collecting data, we conducted a multiple logistic regression analysis to examine factors that were associated with SRBH, with calculations for adjusted odds ratios (ORs) and 95 % confidence intervals (CIs). The study model included a range of individual socioeconomic characteristics, work-related variables, health behaviors, and health conditions. Results: Although the associated factors varied according to age group, several factors generally related to SRBH, including the lack of exercise, stress, having one or more chronic diseases, and work-related pain. By contrast, neither sex nor sleep duration were associated with SRBH of respondents. Monthly night work, smoking, and alcohol consumption were only associated with SRBH of certain age groups. Conclusions: Several variables clearly related to SRBH of police officers. In this context, health-related associations, especially stress and chronic diseases, tended to differ according to age, including those that should be considered to improve health. These findings have important implications for relevant healthcare programs and interventions.

Comparison of three-dimensional printed resin crowns and preformed stainless steel crowns for primary molar restorations: a randomized controlled trial.

The importance of aesthetics in children has increased over time. Therefore, this multicenter randomized clinical trial aimed to analyze and compare three-dimensional (3D)-printed resin crowns (RCs) as a potential alternative to stainless-steel crowns (SSCs) for restoring primary molars with extensive carious lesions. According to the null hypothesis, no statistically significant difference was observed in restoration failure between RC and SSC groups. A total of 56 primary molars after pulp treatment at two dental hospitals were included. After pulp treatment, the teeth were randomly divided into two groups: SSCs (n = 28) and RCs (n = 28). At 1 week and 3, 6 and 12 months, the Quigley-Hein plaque index (QHI), gingival index (GI), occlusal wear, and survival rate were assessed by examination, radiography and alginate impressions. No significant difference in QHI was observed between the two groups. However, the GI at 12 months and occlusal wear in the RC group were significantly higher than those in the SSC group (p < 0.05). The survival rates were 100% in the SSC group and 82.1% in the RC group (p = 0.047). Cracks and discoloration were also observed in the RCs. Within the limitations of this study, 3D-printed RCs are aesthetically superior to SSCs and clinically easy to repair. However, if clinical effectiveness and safety are improved, RCs could potentially become a viable aesthetic alternative in the future.

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.

Automatic assessment of bowel preparation by an artificial intelligence model and its clinical applicability.

BACKGROUND AND AIM: Reliable bowel preparation assessment is important in colonoscopy. However, current scoring systems are limited by laborious and time-consuming tasks and interobserver variability. We aimed to develop an artificial intelligence (AI) model to assess bowel cleanliness and evaluate its clinical applicability. METHODS: A still image-driven AI model to assess the Boston Bowel Preparation Scale (BBPS) was developed and validated using 2361 colonoscopy images. For evaluating real-world applicability, the model was validated using 113 10-s colonoscopy video clips and 30 full colonoscopy videos to identify "adequate (BBPS 2-3)" or "inadequate (BBPS 0-1)" preparation. The model was tested with an external dataset of 29 colonoscopy videos. The clinical applicability of the model was evaluated using 225 consecutive colonoscopies. Inter-rater variability was analyzed between the AI model and endoscopists. RESULTS: The AI model achieved an accuracy of 94.0% and an area under the receiver operating characteristic curve of 0.939 with the still images. Model testing with an external dataset showed an accuracy of 95.3%, an area under the receiver operating characteristic curve of 0.976, and a sensitivity of 100% for the detection of inadequate preparations. The clinical applicability study showed an overall agreement rate of 85.3% between endoscopists and the AI model, with Fleiss' kappa of 0.686. The agreement rate was lower for the right colon compared with the transverse and left colon, with Fleiss' kappa of 0.563, 0.575, and 0.789, respectively. CONCLUSIONS: The AI model demonstrated accurate bowel preparation assessment and substantial agreement with endoscopists. Further refinement of the AI model is warranted for effective monitoring of qualified colonoscopy in large-scale screening programs.

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.