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Abstract Human skin samples for microbiome analysis are traditionally collected using a non-invasive swabbing method. Here, we compared the differences in bacterial community structures on scalp hair and scalps with samples collected using non-invasive swabbing and cutting/removal of scalp hair in 12 individuals. Hair-related samples, such as hair shafts and hair swabs, had significantly higher alpha diversity than scalp swab samples, whereas there were no significant differences between hair shafts and hair swabs. The relative abundances of the three major phyla and five major operational taxonomic units were not significantly different between the hair shaft and hair swab samples. The principal coordinate analysis plots based on weighted UniFrac distances were grouped into two clusters: samples from hair-related areas and scalp swabs, and there were significant differences only between samples from hair-related areas and scalp swabs. In addition, a weighted UniFrac analysis revealed that the sampling site-based category was a statistical category but not a hair sampling method-based category. These results suggest that scalp hair bacteria collected using non-invasive swab sampling were comparable to those collected cutting/removal of scalp hair.

Summary: Localization to the endoplasmic reticulum (ER) and subsequent disulfide bond formation are crucial processes governing the biogenesis of secretory pathway proteins in eukaryotes. Hence, comprehending the mechanisms underlying these processes is important. Here, we have engineered firefly luciferase (FLuc) as a tool to detect deficiencies in these processes within mammalian cells. To achieve this, we introduced multiple cysteine substitutions into FLuc and targeted it to the ER. The reporter exhibited FLuc activity in response to defects in protein localization or disulfide bond formation within the ER. Notably, this system exhibited outstanding sensitivity, reproducibility, and convenience in detecting abnormalities in these processes. We applied this system to observe a protein translocation defect induced by an inhibitor of HIV receptor biogenesis. Moreover, utilizing the system, we showed that modulating LMF1 levels dramatically impacted the ER’s redox environment, confirming that LMF1 plays some critical role in the redox control of the ER.

Background: Crab-flavored seafood is a well-known traditional Japanese product that is sold as “imitation crab” worldwide. Although it is a low-cost, low-fat, high-protein food, there are few data on its potential health benefits. Here, we have assessed the effects of crab-flavored seafood consumption on organ weight and serum biomarkers levels in rats. Methods: Sprague–Dawley rats (male; aged 6 weeks) were fed a normal diet (n = 8) or a normal diet with 5% dried crab-flavored seafood (n = 8) for 84 days. Food intake and overall body weight were measured every week; organ weight and blood biochemistry were evaluated at the end of the administration period. Results: After 84 days, there were no significant differences in food intake, overall body weight, or organ weight between the 2 groups; however, the muscle weight of rats fed crab-flavored seafood tended to be higher than that of rats fed the normal diet. Several serum biomarkers did not differ between the 2 groups, but serum high-density lipoprotein, total bilirubin, and indirect bilirubin levels were significantly raised in rats fed crab-flavored seafood. Moreover, blood urea nitrogen was significantly lower, and some liver function parameters tended to be lower in rats fed crab-flavored seafood. Conclusions: Consumption of crab-flavored seafood may be effective for promoting muscle protein synthesis and improving serum biomarkers associated with disorders such as cardiovascular disease and stroke. Thus, crab-flavored seafood may have application as a functional food for the global management of human health.

EISCAT_3D is a project to build a multi-site phased-array incoherent scatter radar system in northern Fenno-Scandinavia. We demonstrate via numerical simulation how useful monochromatic images taken by a multi-point imager network are for auroral research in the EISCAT_3D project. We apply the generalized aurora computed tomography (G-ACT) method to modelled observational data from real instruments, such as the Auroral Large Imaging System (ALIS) and the EISCAT_3D radar. G-ACT is a method for reconstructing the three-dimensional (3D) distribution of auroral emissions and ionospheric electron density (corresponding to the horizontal two-dimensional (2D) distribution of energy spectra of precipitating electrons) from multi-instrument data. It is assumed that the EISCAT_3D radar scans an area of 0.8° in geographic latitude and 3° in longitude at an altitude of 130 km with 10 × 10 beams from the radar core site at Skibotn (69.35° N, 20.37° E). Two neighboring discrete arcs are assumed to appear in the observation region of the EISCAT_3D radar. The reconstruction results from G-ACT are compared with those from the normal ACT as well as the ionospheric electron density from the radar. It is found that G-ACT can interpolate the ionospheric electron density at a much higher spatial resolution than that observed by the EISCAT_3D radar. Furthermore, the multiple arcs reconstructed by G-ACT are more precise than those by ACT. In particular, underestimation of the ionospheric electron density and precipitating electrons' energy fluxes inside the arcs is significantly improved by G-ACT including the EISCAT_3D data. Even when the ACT reconstruction is difficult due to the unsuitable locations of the imager sites relative to the discrete arcs and/or a small number of available images, G-ACT allows us to obtain better reconstruction results.

To assess the risk of food allergies in foods processed under the Japanese food labeling system, estimating exposure to hidden allergens is necessary. We assessed exposure to egg protein in foods processed according to the Japanese food labeling system. First, we estimated the concentration distribution of egg protein by Bayesian methods using data from the literature and the measurement of food products with precautional declarations in the labeling margin. We then estimated the food-intake portion-size distribution under two scenarios: soft drink consumption as an example of single, high-intake consumption, and confections, which are frequently consumed by children, as a realistic example of low-intake consumption. Finally, we estimated the distribution of unexpected intake of egg proteins in the form of single consumption. The mean exposure to egg protein under the high-intake scenario was estimated to be 0.0164 mg for 1–15-year-olds, 0.0171 mg for 4–15-year-olds, 0.0181 mg for 7–15-year-olds, and ≥0.0188 mg for 16-year-olds. The mean exposure to egg protein under the low-intake scenario was estimated to be 0.0018 mg for 1–15-year-olds, 0.0019 mg for 4–15-year-olds, 0.0020 mg for 7–15-year-olds, and ≥0.0022 mg for 16-year-olds. Compared to the reference dose of 2.0 mg proposed by the Joint the Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee, the risk of onset of food allergies due to egg protein contamination from foods without egg labeling is considered to be extremely low under the current Japanese food labeling system.

Abstract This paper describes the instrumentation and the first results of an upper atmospheric observing project conducted in New Zealand. We operate an all-sky aurora camera and a 64-Hz sampling induction magnetometer at Middlemarch, as well as 1-Hz sampling fluxgate magnetometers which have been operative at three stations in New Zealand, Middlemarch, Eyrewell and Te Wharau. Green and red auroras corresponding to the 557.7 nm and 630.0 nm emissions, respectively, were observed on the night of 5 August 2019. Pc1 pulsations were observed in the frequency range of ~ 0.2–1 Hz before and after a small (minimum Dst = − 40 nT) geomagnetic storm during 4–6 October 2020. Before the geomagnetic storm, Pc1 pulsations with several center frequencies were observed regardless of local time. During the recovery phase, an IPDP (interval of pulsations of diminishing period) type of Pc1 and four subsequent intervals of Pc1s were detected. The Ionospheric Alfvén Resonator (IAR) was also identified with spectral resonance structures during this magnetic storm. Lower harmonic modes of the IAR were present throughout the local nighttime, but higher harmonic modes with frequency of 5–15 Hz seemed to disappear at the onset time of substorms. This is the first report of the IAR at such a high frequency range and this is the first IAR observation in the southern hemisphere. Examples of applying cross-phase analysis to observation data of fluxgate magnetometers are also given. Graphical Abstract

Background and objectiveGilteritinib is a novel, highly selective tyrosine kinase inhibitor approved in the USA, Canada, Europe, Brazil, Korea, and Japan for the treatment of FLT3 mutation-positive acute myeloid leukemia. This article describes the clinical pharmacokinetic profile of gilteritinib.MethodsThe pharmacokinetic profile of gilteritinib was assessed from five clinical studies.ResultsDose-proportional pharmacokinetics was observed following once-daily gilteritinib administration (dose range 20-450 mg). Median maximum concentration was reached 2-6 h following single and repeat dosing of gilteritinib; mean elimination half-life was 113 h. Elimination was primarily via feces. Exposure to gilteritinib was comparable under fasted and fed conditions. Gilteritinib is primarily metabolized via cytochrome P450 (CYP) 3A4; coadministration of gilteritinib with itraconazole (a strong P-glycoprotein inhibitor and CYP3A4 inhibitor) or rifampicin (a strong P-glycoprotein inducer and CYP3A inducer) significantly affected the gilteritinib pharmacokinetic profile. No clinically relevant interactions were observed when gilteritinib was coadministered with midazolam (a CYP3A4 substrate) or cephalexin (a multidrug and toxin extrusion 1 substrate). Unbound gilteritinib exposure was similar between subjects with hepatic impairment and normal hepatic function.ConclusionsGilteritinib exhibits a dose-proportional pharmacokinetic profile in healthy subjects and in patients with relapsed/refractory acute myeloid leukemia. Gilteritinib exposure is not significantly affected by food. Moderate-to-strong CYP3A inhibitors demonstrated a significant effect on gilteritinib exposure. Coadministration of gilteritinib with CYP3A4 or multidrug and toxin extrusion 1 substrates did not impact substrate concentrations. Unbound gilteritinib was comparable between subjects with hepatic impairment and normal hepatic function; dose adjustment is not warranted for patients with hepatic impairment.Clinical trial registrationNCT02014558, NCT02456883, NCT02571816.

The north–south (NS) anisotropy of galactic cosmic rays (GCRs) is dominated by a diamagnetic drift flow of GCRs in the interplanetary magnetic field (IMF), allowing us to derive key parameters of cosmic-ray propagation, such as the density gradient and diffusion coefficient. We propose a new method to analyze the rigidity spectrum of GCR anisotropy and reveal a solar cycle variation of the NS anisotropy’s spectrum using ground-based muon detectors in Nagoya, Japan, and Hobart, Australia. The physics-based correction method for the atmospheric temperature effect on muons is used to combine the different-site detectors free from local atmospheric effects. NS channel pairs in the multidirectional muon detectors are formed to enhance sensitivity to the NS anisotropy, and in this process, general graph matching in graph theory is introduced to survey optimized pairs. Moreover, Bayesian estimation with the Gaussian process allows us to unfold the rigidity spectrum without supposing any analytical function for the spectral shape. Thanks to these novel approaches, it has been discovered that the rigidity spectrum of the NS anisotropy is dynamically varying with solar activity every year. It is attributed to a rigidity-dependent variation of the radial density gradient of GCRs based on the nature of the diamagnetic drift in the IMF. The diffusion coefficient and mean free path length of GCRs as functions of the rigidity are also derived from the diffusion–convection flow balance. This analysis expands the estimation limit of the mean free path length into the ≤200 GV rigidity region from the

This paper presents the global analysis of two extended decreases in the galactic cosmic-ray intensity observed by worldwide networks of ground-based detectors in 2012. This analysis is capable of separately deriving the cosmic-ray density (or omnidirectional intensity) and anisotropy, each as a function of time and rigidity. A simple diffusion model along the spiral field line between Earth and a cosmic-ray barrier indicates the long duration of these events, resulting from about 190° eastern extent of a barrier such as an interplanetary shock followed by the sheath region and/or the corotating interaction region (CIR). It is suggested that the coronal mass ejection merging with and compressing the preexisting CIR at its flank can produce such an extended barrier. The derived rigidity spectra of the density and anisotropy both vary in time during each event period. In particular we find that the temporal feature of the “phantom Forbush decrease (FD)” reported in an analyzed period is dependent on rigidity, and looks quite different at different rigidities. From these rigidity spectra of the density and anisotropy, we derive the rigidity spectrum of the average parallel mean free path of pitch angle scattering along the spiral field line and infer the power spectrum of the magnetic fluctuation and its temporal variation. The possible physical cause of the strong rigidity dependence of the phantom FD is also discussed. These results demonstrate the high-energy cosmic rays observed at Earth responding to remote space weather.

Abstract Objective We studied the prognosis and clinicopathological background of lung adenocarcinoma predominance among patients who underwent lobectomy using data from the Japanese Joint Committee of Lung Cancer Registry. Methods Two thousand eight hundred sixty-three cases were extracted. Recurrence free survival (RFS) rates, overall survival (OS) rates and clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status were examined. Results Median follow-up period was 65.5 months. Adenocarcinoma predominance was sub-grouped according to OS and RFS rate. In pathological stage I, 5-year RFS and OS rates were respectively 92.2% and 95.8% in group A (adenocarcinoma-in-situ + minimally invasive adenocarcinoma), 89.3% and 92.1% in group B (lepidic), 79.2% and 89.7% in group C (papillary + acinar + variants) and 69.0% and 79.0% in group D (solid + micropapillary). In pathological stage II + IIIA, they were, 43.6% and 72.4% in B, 39.5% and 66.9% in C and 31.0% and 53.7% in D. Group D showed significant worst outcome both in stage I and II + IIIA. Up stage rate from clinical stage I to pathological stage II + IIIA was 0.0%, 3.7%, 15.9% and 33.3%. The frequency of lymph-vessel, vascular, pleura invasion and positive EGFR mutation were 0.0%, 0.0%, 0.0% and 57.1% in group A, 15.6%, 10.0%, 12.1% and 55.1% in B, 36.6%, 31.8%, 29.7% and 44.9% in C, 50.2%, 57.8%, 38.9% and 21.3% in D. In group D, lymph-vessel, vascular and pleura invasion were most, EGFR mutation was least frequent not only in pathological stage I but also stage II + IIIA. In multivariate analysis, age, pathological stage, vascular invasion, and group D were independent factors affected RFS and OS. Conclusion Limited to lobectomy cases, solid + micropapillary was independent prognostic factor both in early and locally advanced stage. Its malignant degree was related to the frequency of pathological invasive factors and EGFR mutation status.

Abstract Background The present study aimed to examine the correlation between preoperative carcinoembryonic antigen levels in pancreatic juice (PJ‐CEA) and the histological subtype of intraductal papillary mucinous neoplasm (IPMN). Methods We enrolled IPMN patients who underwent endoscopic retrograde pancreatography between March 2002 and March 2018. Clinical factors associated with IPMN histological subtypes of 67 patients who underwent surgery were analyzed. Furthermore, the relationship between CEA immunohistochemistry findings and histological subtypes was investigated. Results Median PJ‐CEA were 15 ng/ml in the gastric type, 150 ng/ml in the intestinal type, and 175 ng/ml in the pancreatobiliary type. Both intestinal and pancreatobiliary types had significantly higher PJ‐CEA than the gastric type (p = 0.001). In the analysis of histological subtype predictors, high PJ‐CEA (≥63 ng/ml) only showed a significant difference in multivariate analyses (95% confidence interval 4.8–70.2; p < 0.001). Immunohistochemistry findings revealed significantly higher CEA expression in the non‐gastric type than in the gastric type (p < 0.001). The non‐gastric type showed a significantly worse prognosis than the gastric type (p = 0.017). Conclusion PJ‐CEA was an independent predictor of IPMN histological subtypes in a preoperative setting. High PJ‐CEA predict the non‐gastric type, while low PJ‐CEA predict the gastric type.

Background: Crab-flavored seafood is a well-known traditional Japanese product that is sold as "imitation crab" worldwide. Although it is a low-cost, low-fat, high-protein food, there are few data on its potential health benefits. Here, we have assessed the effects of crab-flavored seafood consumption on organ weight and serum biomarkers levels in rats. Methods: Sprague–Dawley rats (male; aged 6 weeks) were fed a normal diet (n = 8) or a normal diet with 5% dried crab-flavored seafood (n = 8) for 84 days. Food intake and overall body weight were measured every week; organ weight and blood biochemistry were evaluated at the end of the administration period. Results: After 84 days, there were no significant differences in food intake, overall body weight, or organ weight between the 2 groups; however, the muscle weight of rats fed crab-flavored seafood tended to be higher than that of rats fed the normal diet. Several serum biomarkers did not differ between the 2 groups, but serum high-density lipoprotein, total bilirubin, and indirect bilirubin levels were significantly raised in rats fed crab-flavored seafood. Moreover, blood urea nitrogen was significantly lower, and some liver function parameters tended to be lower in rats fed crab-flavored seafood. Conclusions: Consumption of crab-flavored seafood may be effective for promoting muscle protein synthesis and improving serum biomarkers associated with disorders such as cardiovascular disease and stroke. Thus, crab-flavored seafood may have application as a functional food for the global management of human health. [ABSTRACT FROM AUTHOR]