infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate
can reduce the risk of gastric cancer in persons with a family history of ...gastric cancer in first-degree relatives is unknown.
In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with
infection to receive either eradication therapy (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to
eradication status, assessed during the follow-up period.
A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval CI, 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent
infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom
infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001).
Among persons with
infection who had a family history of gastric cancer in first-degree relatives,
eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 ...dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication. Although fatalities were not observed, SARS-CoV-2-infected ferrets shed virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. At 2 days post-contact, SARS-CoV-2 was detected in all naive direct contact ferrets. Furthermore, a few naive indirect contact ferrets were positive for viral RNA, suggesting airborne transmission. Viral antigens were detected in nasal turbinate, trachea, lungs, and intestine with acute bronchiolitis present in infected lungs. Thus, ferrets represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.
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•SARS-CoV-2-infected ferrets exhibit elevated body temperature and virus replication•SARS-CoV-2 is shed in nasal washes, saliva, urine and feces•SARS-CoV-2 is effectively transmitted to naive ferrets by direct contact•SARS-CoV-2 infection leads acute bronchiolitis in infected ferrets
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spreads, leading to a pandemic infection. Kim et al. show that ferrets are highly susceptible to SARS-CoV-2 infection and effectively transmit the virus by direct or indirect contact, recapitulating human infection and transmission.
The previous outbreaks of SARS-CoV and MERS-CoV have led researchers to study the role of diagnostics in impediment of further spread and transmission. With the recent emergence of the novel ...SARS-CoV-2, the availability of rapid, sensitive, and reliable diagnostic methods is essential for disease control. Hence, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the specific detection of SARS-CoV-2. The primer sets for RT-LAMP assay were designed to target the nucleocapsid gene of the viral RNA, and displayed a detection limit of 10
2
RNA copies close to that of qRT-PCR
.
Notably, the assay has exhibited a rapid detection span of 30 min combined with the colorimetric visualization. This test can detect specifically viral RNAs of the SARS-CoV-2 with no cross-reactivity to related coronaviruses, such as HCoV-229E, HCoV-NL63, HCoV-OC43, and MERS-CoV as well as human infectious influenza viruses (type B, H1N1pdm, H3N2, H5N1, H5N6, H5N8, and H7N9), and other respiratory disease-causing viruses (RSVA, RSVB, ADV, PIV, MPV, and HRV). Furthermore, the developed RT-LAMP assay has been evaluated using specimens collected from COVID-19 patients that exhibited high agreement to the qRT-PCR. Our RT-LAMP assay is simple to perform, less expensive, time-efficient, and can be used in clinical laboratories for preliminary detection of SARS-CoV-2 in suspected patients. In addition to the high sensitivity and specificity, this isothermal amplification conjugated with a single-tube colorimetric detection method may contribute to the public health responses and disease control, especially in the areas with limited laboratory capacities.
Few studies have used a longitudinal approach to describe the immune response to SARS-CoV-2 infection. Here, we perform single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally ...obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment shows distinct changes in cell proportions and characteristics compared to uninfected control, at 2 and 5 days post-infection (dpi). Macrophages are classified into 10 distinct subpopulations with transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, notably at 2 dpi. Moreover, trajectory analysis reveals gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identifies a macrophage subpopulation that has rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we find that M1 or M2 macrophages show distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection.
Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the ...receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.
Patients with early gastric cancers that are limited to gastric mucosa or submucosa usually have an advanced loss of mucosal glandular tissue (glandular atrophy) and are at high risk for subsequent ...(metachronous) development of new gastric cancer. The long-term effects of treatment to eradicate Helicobacter pylori on histologic improvement and the prevention of metachronous gastric cancer remain unclear.
In this prospective, double-blind, placebo-controlled, randomized trial, we assigned 470 patients who had undergone endoscopic resection of early gastric cancer or high-grade adenoma to receive either H. pylori eradication therapy with antibiotics or placebo. Two primary outcomes were the incidence of metachronous gastric cancer detected on endoscopy performed at the 1-year follow-up or later and improvement from baseline in the grade of glandular atrophy in the gastric corpus lesser curvature at the 3-year follow-up.
A total of 396 patients were included in the modified intention-to-treat analysis population (194 in the treatment group and 202 in placebo group). During a median follow-up of 5.9 years, metachronous gastric cancer developed in 14 patients (7.2%) in the treatment group and in 27 patients (13.4%) in the placebo group (hazard ratio in the treatment group, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.03). Among the 327 patients in the subgroup that underwent histologic analysis, improvement from baseline in the atrophy grade at the gastric corpus lesser curvature was observed in 48.4% of the patients in the treatment group and in 15.0% of those in the placebo group (P<0.001). There were no serious adverse events; mild adverse events were more common in the treatment group (42.0% vs. 10.2%, P<0.001).
Patients with early gastric cancer who received H. pylori treatment had lower rates of metachronous gastric cancer and more improvement from baseline in the grade of gastric corpus atrophy than patients who received placebo. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT02407119 .).
The human gut hosts a diverse community of bacteria referred to as the gut microbiome. We investigated the association between the relative abundance of gastric microbiota and gastric cancer (GC) ...risk in a Korean population. The study participants included 268 GC patients and 288 controls. DNA was extracted from gastric biopsies, and 16S rRNA gene analysis was performed. Unconditional logistic regression models were used to observe the associations. Of the participants, those who had the highest level (highest tertile) of relative Helicobacter pylori and Propionibacterium acnes abundances showed a significantly higher risk for GC after adjusting for potential confounding variables (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.17-2.97, p for trend = 0.017 and OR = 4.77, 95% CI = 2.94-7.74, p for trend <0.001, respectively). Subjects who carried Prevotella copri had a significantly higher risk of GC than noncarriers (OR = 2.54, 95% CI = 1.42-4.55, p for trend = 0.002). There was a lower risk of GC in subjects carrying Lactococcus lactis than in noncarriers (OR = 0.21, 95% CI = 0.10-0.44, p for trend <0.001). H. pylori, P. acnes and P. copri are strong risk factors, whereas L. lactis is a protective factor, for GC development in Koreans. Further microbiome studies are warranted to verify the findings of the current study.
Background
While the clinical characteristics and outcomes of asthma‐chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the ...prevalence and features of ACO in patients with severe asthma are unclear.
Objectives
Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry.
Methods
At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non‐ACO groups, and the demographic and clinical characteristics of these two groups were compared.
Results
Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex‐ or current smokers (P < .001) compared with those in the non‐ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non‐ACO group. The ACO group used more inhaled long‐acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006).
Conclusion
Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.
We found that about one‐fourth of patients with severe asthma was diagnosed with ACO by specialists. The most common reason for ACO diagnosis was smoking history. ACO patients were predominantly male, older, and had more smoking history compared with non‐ACO patients. ACO patients had higher blood neutrophil count, but lower lung function. ACO patients used more LAMA, methylxanthine, and systemic corticosteroid and had more frequent exacerbations related to ER visits compared with those with severe asthma only. Abbreviations: ACO, asthma‐COPD overlap; ER, emergency room; FEV1, forced expiratory volume in one second.
Water discharges at hydroelectric dams on the Imjin River, which flows through North and South Korea, generate abrupt water level increases downstream. We assessed infrasound signals from water ...discharges using an infrasound array located ∼32 km from the source and applied infrasound detection in a flash flood alert system. Using infrasound signals, there was a 79% detection rate for 48 water level increase events occurring in the river downstream during a 14‐year period (2008–2021). The detected signals had a low amplitude, long duration, and broad frequency range (0.5–15 Hz). The energy curves of the detected infrasound signals for selected events showed good correlations with the onset times and water level variations in water level records. These results demonstrate that infrasound monitoring can serve as a practical early warning system for impending flash floods resulting from unnoticed water discharges or sudden debris flows in mountainous regions.
Plain Language Summary
Infrasound waves are low‐frequency atmospheric acoustic waves that travel long distances due to low energy loss. Infrasound can be generated from various natural and anthropogenic phenomena. Water dam discharges and waterfalls produce infrasound waves in the atmosphere by converting the potential energy of the massive amount of water to acoustic energy during the collision of water masses at the water pool. We analyzed infrasound signals from water dam discharge events and found that low‐amplitude coherent signals could be detected and recorded as characteristic signals at a remote infrasound sensor array. The infrasound detection parameters can be correlated with water level rise onset times and variations recorded downstream. Similar to earthquake early warning systems, infrasound monitoring can be used to provide prompt alerts of flash floods resulting from unexpected dam discharges or substantial debris flows in mountainous regions, which would enhance civil protection in riverside downstream areas.
Key Points
Water discharges at hydroelectric dams generate low‐amplitude, coherent infrasound waves that can be detected at a remote infrasound array
In a study area, 79% of 48 water level rise events for 14 years can be associated with water discharges at a dam by infrasound detection
Infrasound arrays can be potentially used to provide prompt alerts of flash flooding resulting from unexpected dam discharges
Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10-20%, no effective vaccines are currently ...available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection.
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