Pediatric Respiratory Virus Infections During the COVID-19 Pandemic in a Region Without Active Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Circulation

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were not prevalent in Yonago and its vicinity during autumn 2020, and the relative frequencies of pathogen-induced respiratory infections during this period are unclear. Methods: We collected 109 nasopharyngeal swabs from 93 pediatric patients who visited Tottori University Hospital between October 1, 2020, and March 31, 2021. These samples were comprehensively tested for 18 pathogens with the FilmArray® respiratory panel test (v2.1) using nested real-time polymerase chain reaction, and the frequency of pathogens detected per month was calculated. In addition, we compared the duration of fever and the blood test results of patients infected with each pathogen or multiple pathogens. Results: Of the 109 samples, 42 were obtained from female patients and 67 from male patients (median age, 3 years; range, 0-15 years). Overall, 62 patients (56.9%) had a fever ≥ 38 °C at the time of examination, and the median duration of fever ≥ 38 °C was 2 days (1-12). During the study period, the highest number of samples (22) were collected in November 2020. Among samples that tested positive, the most common pathogens were rhino/enteroviruses (52 samples; 76.5%), followed by adenoviruses (7 samples; 10.3%), coronavirus NL63 (6 samples; 8.8%), coronavirus OC43, parainfluenza virus type 1, and parainfluenza virus type 2 (1 sample each; 1.5% each). The duration of fever was significantly longer in adenovirus-infected patients than in patients infected with other viruses (P < 0.05). Hemoglobin and sodium levels were also significantly lower among the adenovirus-infected patients. However, these variations were mostly within the normal range. No clinically meaningful differences were found between rhino/enterovirus-infected and non-rhino/enterovirus-infected cases, between coronavirus NL63-infected and non-coronavirus NL63-infected cases, and between cases with multiple- and single-pathogen infections. Conclusion: Rhino/enteroviruses were the most common viruses causing respiratory tract infections in areas without endemic SARS-CoV-2

Gastric Carcinoid with Hypergastrinemia: Report of Three Cases

We report 3 cases of gastric carcinoids with hypergastrinemia. Case 1: A 60-year-old man had a 2 cm carcinoid of the stomach and underwent partial resection. Involvement of the muscularis propria and lymph nodes metastasis were observed microscopically. Follow-up gastroscopy revealed another carcinoid lesion and total gastrectomy was performed. Case 2: A 67-year-old woman with multiple carcinoids of the entire stomach underwent antrectomy. No growth of residual tumors has been detected so far. Case 3: A 61-year-old man had a tumor near the esophagogastric junction and underwent total gastrectomy. Carcinoid component was diffusely intermingled with adenocarcinoma in the tumor and invaded into the subserosa. In all 3 cases, the serum gastrin level was high and atrophic gastritis was microscopically observed. Carcinoid tumor in Case 3 was different from those in Cases 1 and 2 and interestingly, gastric carcinoid with hypergastrinemia showed various types of appearance

UTM and D-NET: NASA and JAXA's Collaborative Research on Integrating Small UAS with Disaster Response Efforts

Natural disasters, such as flooding, wildfire, hurricane, tornadoes, earthquakes and tsunamis, pose challenges in preserving human life and minimizing the damages to a region. During catastrophic events, timely response of disaster relief personnel, an efficient deployment of resources in the recovery effort, and coordinated information sharing amongst different relief agencies can make a substantial difference in responding to those impacted by the disaster. Many relief activities currently utilize both ground personnel and manned airborne assets during different phases of the disaster response. Typically, multiple organizations support relief activities and this often creates logistics coordination challenges between agencies which can result in wasted time or resources. The Japan Aerospace Exploration Agency (JAXA) has been developing an "Integrated aircraft operation system for disaster relief (D-NET)", which assists collection and sharing of disaster information through the integrated operation of aircraft such as helicopters, aircraft, and satellites, for efficient and safe rescue operations by disaster relief aircraft. Due to the advancement in unmanned aircraft systems (UAS) technologies, public safety organizations have started incorporating small UAS (sUAS) as an asset in their disasters response activities. To address the airspace integration challenges of the influx of sUAS in the United States the National Aeronautics and Space Administration (NASA), under the UAS Traffic Management (UTM) project, has been engaged in research to enable large-scale commercial applications of sUAS operating in low altitude airspace. This paper presents the integration of D-NET, which incorporate sUAS in the planning, information sharing, and operation support of disasters response activities, and UTM, which provides airspace management to enable large scale high density operations. The integration of the DNET and UTM systems enables coordination, data sharing, and airspace management to improve the timeliness of the disaster response, enable relief organization to reduce cost and overhead by using UAS assets and still maintain airspace safety during the relief activities

Fermionic solutions of chiral Gross-Neveu and Bogoliubov-de Gennes systems in nonlinear Schr\"odinger hierarchy

The chiral Gross-Neveu model or equivalently the linearized Bogoliubov-de Gennes equation has been mapped to the nonlinear Schr\"odinger (NLS) hierarchy in the Ablowitz-Kaup-Newell-Segur formalism by Correa, Dunne and Plyushchay. We derive the general expression for exact fermionic solutions for all gap functions in the arbitrary order of the NLS hierarchy. We also find that the energy spectrum of the n-th NLS hierarchy generally has n+1 gaps. As an illustration, we present the self-consistent two-complex-kink solution with four real parameters and two fermion bound states. The two kinks can be placed at any position and have phase shifts. When the two kinks are well separated, the fermion bound states are localized around each kink in most parameter region. When two kinks with phase shifts close to each other are placed at distance as short as possible, the both fermion bound states have two peaks at the two kinks, i.e., the delocalization of the bound states occurs.Comment: 7 pages, 1 figure, Phys. Lett. B, in pres

Spectral evolution of GRB 060904A observed with Swift and Suzaku -- Possibility of Inefficient Electron Acceleration

We observed an X-ray afterglow of GRB 060904A with the Swift and Suzaku satellites. We found rapid spectral softening during both the prompt tail phase and the decline phase of an X-ray flare in the BAT and XRT data. The observed spectra were fit by power-law photon indices which rapidly changed from $\Gamma = 1.51^{+0.04}_{-0.03}$ to $\Gamma = 5.30^{+0.69}_{-0.59}$ within a few hundred seconds in the prompt tail. This is one of the steepest X-ray spectra ever observed, making it quite difficult to explain by simple electron acceleration and synchrotron radiation. Then, we applied an alternative spectral fitting using a broken power-law with exponential cutoff (BPEC) model. It is valid to consider the situation that the cutoff energy is equivalent to the synchrotron frequency of the maximum energy electrons in their energy distribution. Since the spectral cutoff appears in the soft X-ray band, we conclude the electron acceleration has been inefficient in the internal shocks of GRB 060904A. These cutoff spectra suddenly disappeared at the transition time from the prompt tail phase to the shallow decay one. After that, typical afterglow spectra with the photon indices of 2.0 are continuously and preciously monitored by both XRT and Suzaku/XIS up to 1 day since the burst trigger time. We could successfully trace the temporal history of two characteristic break energies (peak energy and cutoff energy) and they show the time dependence of $\propto t^{-3} \sim t^{-4}$ while the following afterglow spectra are quite stable. This fact indicates that the emitting material of prompt tail is due to completely different dynamics from the shallow decay component. Therefore we conclude the emission sites of two distinct phenomena obviously differ from each other.Comment: 19 pages, 9 figures, accepted for publication in PASJ (Suzaku 2nd Special Issue

Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts

Idiopathic pulmonary fibrosis is a chronic intractable lung disease, leading to　respiratory failure and death. Although anti-fibrotic agents delay disease progression, they are not considered curative treatments, and alternative modalities have attracted attention. We examined the effect of human γδ T cells on collagen type I in lung fibroblasts. Collagen type I was markedly reduced in a γδ T cell number-dependent manner following treatment with γδ T cells expanded with tetrakis-pivaloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2. Collagen type I levels remained unchanged on addition of γδ T cells to the culture system through a trans-well culture membrane, suggesting that cell–cell contact is essential for reducing its levels in lung fibroblasts. Re-stimulating γδ T cells with (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) reduced collagen type I levels without cell–cell contact, indicating the existence of HMBPP-induced soluble anti-fibrotic factors in γδ T cells. Adding anti-interferon-γ (IFN-γ)-neutralizing mAb restored collagen type I levels, demonstrating that human γδ T cell-derived IFN-γ reduces collagen type I levels. Conversely, interleukin-18 augmented γδ T cell-induced suppression of collagen type I. Therefore, human γδ T cells reduce collagen levels in lung fibroblasts via two distinct mechanisms; adoptive γδ T cell transfer is potentially a new therapeutic candidate

Novel SPEF2 Variant in a Japanese Patient with Primary Ciliary Dyskinesia: A Case Report and Literature Review

Primary ciliary dyskinesia (PCD) is a genetic and congenital disease associated with an abnormal ciliary ultrastructure and function and is estimated to affect 1 in 15,000–20,000 individuals. A PCD diagnosis can be achieved by genotyping. Here, we performed whole-exome analysis for the diagnosis of PCD and described the detailed clinical characteristics of the case. A 39-year-old Japanese woman with sinusitis and bronchiectasis without situs inversus had had upper and lower respiratory symptoms since childhood and had received long-term macrolide therapy without an accurate diagnosis. A moderate deterioration of cilia function was observed by high-speed video microscopy analysis; additionally, the number of cells with moving cilia was fewer than that in patients without PCD. Electron microscopy revealed no apparent structural abnormalities. We performedwhole-exome analysis and identified novel biallelic variants of SPEF2 in the homozygous state (c.1860_1861insCT).We confirmed the absence of SPEF2 protein expression in the cilia of the nasal mucosa using fluorescent immunostaining. Accordingly, she was diagnosed as having PCD with the SPEF2 variant. The present case suggests that the deterioration of cilia function is moderate, the number of respiratory cells with moving cilia might be reduced, and the respiratory condition could be severe in patients with PCD with the SPEF2 variant

Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population

Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS, which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7β-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population.Tomofuji Yoshihiko, Kishikawa Toshihiro, Sonehara Kyuto, et al. Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population. Cell Reports 42, 113324 (2023); https://doi.org/10.1016/j.celrep.2023.113324

Cross-Protective Potential of a Novel Monoclonal Antibody Directed against Antigenic Site B of the Hemagglutinin of Influenza A Viruses

The hemagglutinin (HA) of influenza A viruses has been classified into sixteen distinct subtypes (H1–H16) to date. The HA subtypes of influenza A viruses are principally defined as serotypes determined by neutralization or hemagglutination inhibition tests using polyclonal antisera to the respective HA subtypes, which have little cross-reactivity to the other HA subtypes. Thus, it is generally believed that the neutralizing antibodies are not broadly cross-reactive among HA subtypes. In this study, we generated a novel monoclonal antibody (MAb) specific to HA, designated MAb S139/1, which showed heterosubtypic cross-reactive neutralization and hemagglutination inhibition of influenza A viruses. This MAb was found to have broad reactivity to many other viruses (H1, H2, H3, H5, H9, and H13 subtypes) in enzyme-linked immunosorbent assays. We further found that MAb S139/1 showed neutralization and hemagglutination-inhibition activities against particular strains of H1, H2, H3, and H13 subtypes of influenza A viruses. Mutant viruses that escaped neutralization by MAb S139/1 were selected from the A/Aichi/2/68 (H3N2), A/Adachi/2/57 (H2N2), and A/WSN/33 (H1N1) strains, and sequence analysis of the HA genes of these escape mutants revealed amino acid substitutions at positions 156, 158, and 193 (H3 numbering). A molecular modeling study showed that these amino acids were located on the globular head of the HA and formed a novel conformational epitope adjacent to the receptor-binding domain of HA. Furthermore, passive immunization of mice with MAb S139/1 provided heterosubtypic protection. These results demonstrate that MAb S139/1 binds to a common antigenic site shared among a variety of HA subtypes and neutralizes viral infectivity in vitro and in vivo by affecting viral attachment to cells. The present study supports the notion that cross-reactive antibodies play some roles in heterosubtypic immunity against influenza A virus infection, and underscores the potential therapeutic utility of cross-reactive antibodies against influenza