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In chickens, primordial germ cells (PGCs) are effective targets for advanced genome editing, including gene knock-in. Although a long-term culture system has been established for chicken PGCs, it is necessary to select a gene-editing tool that is efficient and precise for editing the PGC genome while maintaining its ability to contribute to the reproductive system. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and CRISPR-mediated precise integration into the target chromosome (CRIS-PITCh) methods are superior as the donor vector is easier to construct, has high genome editing efficiency, and does not select target cells, compared to the homologous recombination method, which has been conventionally used to generate knock-in chickens. In this study, we engineered knock-in chicken PGCs by integrating a fluorescent protein gene cassette as a fusion protein into the chicken vasa homolog ( CVH ) locus of chicken PGCs using the CRIS-PITCh method. The knock-in PGCs expressed the fluorescent protein in vitro and in vivo , facilitating the tracking of PGCs. Furthermore, we characterized the efficiency of engineering double knock-in cell lines. Knock-in cell clones were obtained by limiting dilution, and the efficiency of engineering double knock-in cell lines was confirmed by genotyping. We found that 82% of the analyzed clones were successfully knocked-in into both alleles. We suggest that the production of model chicken from the knock-in PGCs can contribute to various studies, such as the elucidation of the fate of germ cells and sex determination in chicken., (2022, Japan Poultry Science Association.)

Extended shelf life (ESL) processing (i.e., heat treatment at 130°C for 2 s) is usually not used for producing set yogurt because of the fragility of the curd structure. We investigated the effects of homogenization conducted at higher pressure than the conventional conditions (10 MPa for the first stage and 5 MPa for the second stage) on the curd structure of set yogurt, with a focus on the fat globule size. Each yogurt mix was adjusted at the range of fat globule sizes from 0.45 μm to 1.1 μm by a homogenizer and then heated at 95°C for 5 min (conventional heat treatment), 120°C for 2 s, ESL processing, or 140°C for 2 s. The yogurt mixes were fermented by a common yogurt starter, and the curd texture of the obtained yogurts was evaluated. We observed that the curd hardness and curd firmness of the yogurt were each negatively correlated with the fat globule size regardless of the heat-treatment temperature. Compared with the curd obtained with conventional heat treatment, the ESL-processed curd was extremely fragile, but significantly smooth. With ESL processing, a curd hardness >40 g, which is a sufficient strength for commercial transport systems, was obtained by making the fat particle size <0.6 µm, using 2-stage homogenization pressure: 35 MPa for the first stage and 5 MPa for the second stage. A microscopy analysis indicated that the smaller fat globules reinforce the network structure. The yogurt made by ESL processing and that created with 35 + 5 MPa homogenization had significant sensory evaluation scores. Our results indicate that the combination of ESL processing and 35 + 5 MPa homogenization is a novel and useful method for manufacturing set yogurt., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Early rehabilitation allows patients to better perform the activities of daily living after hospital discharge. A specialized physical therapist has been assigned as part of the early rehabilitation, but the effectiveness of the program remains unclear. We investigated how early rehabilitation provided by a specialized physical therapist affects ADL in patients with sepsis., Methods: This was a retrospective cohort study. This study's subjects were sepsis patients who entered the advanced emergency critical care center of Shinshu University Hospital between April 2014 and March 2020. Electronic medical records were reviewed to obtain information on demographic characteristics, severity score, primary source of infection, therapeutic medication, the number of days after hospital admittance until rehabilitation begins, length of hospital stay, discharge to home, and an assessment of daily living activities for each patient. The patients were divided into two groups based on whether they were treated before or after a specialized physical therapist had been hired by the advanced emergency critical care center., Results: Assigning a physical therapist to a patient significantly shortened the number of days until rehabilitation began. In a multivariable model, the strongest predictors of return to independent living after hospital discharge were (1) assigning a specialized physical therapist (odds ratio = 2.40; 95% confidence interval = 1.09-5.79; P = 0.050) and (2) the number of days until rehabilitation started (odds ratio = 0.24; 95% confidence interval = 0.08-0.76; P = 0.014)., Conclusions: Assigning a specialized physical therapist to sepsis patients at an advanced emergency critical care center significantly shortened the number of days until a patient can begin rehabilitation after hospital admittance and improved activities of daily living after hospital discharge., Trial Registration: Trial registration [University Hospital Medical Information Network Clinical Trials Registry, number UMIN000040570 (2020/5/28).]., Competing Interests: The authors have declared that no competing interests exist.

The Mucorales fungal genus Rhizopus is used for the industrial production of organic acids, enzymes and fermented foods. The metabolic engineering efficiency of Rhizopus could be improved using gene manipulation; however, exogenous DNA rarely integrates into the host genome. Consequently, a genetic tool for Mucorales fungi needs to be developed. Recently, programmable nucleases that generate DNA double-strand breaks (DSBs) at specific genomic loci have been used for genome editing in various organisms. In this study, we examined gene disruption in Rhizopus oryzae using transcription activator-like effector nucleases (TALENs), with and without exonuclease overexpression. TALENs with an overexpressing exonuclease induced DSBs, followed by target site deletions. Although DSBs are repaired mainly by nonhomologous end joining in most organisms, our results suggested that in R. oryzae microhomology-mediated end joining was the major DSB repair system. Our gene manipulation method using TALENs coupled with exonuclease overexpression contributes to basic scientific knowledge and the metabolic engineering of Rhizopus., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

The dimorphic yeast Yarrowia lipolytica has an ability to assimilate n-alkanes as carbon and energy sources. In this study, the roles of orthologs of Saccharomyces cerevisiae SEC14 family gene SFH2, which we named SFH21, SFH22, SFH23 and SFH24, of Y. lipolytica were investigated. The transcript levels of SFH21, SFH22 and SFH23, determined by RNA-seq analysis, qRT-PCR analysis and northern blot analysis, were found to increase in the presence of n-alkanes. The deletion mutant of SFH21, but not that of SFH22, SFH23 or SFH24, showed defects in growth in the media containing n-alkanes and in filamentous growth on the solid media containing n-alkanes. Additional deletions of SFH22 and SFH23 significantly exaggerated the defect in filamentous growth of the deletion mutant of SFH21, and expression of SFH22 or SFH24 using the SFH21 promoter partially suppressed the growth defect of the deletion mutant of SFH21 on n-alkanes. These results suggest that SFH2 orthologs are involved in the utilization of n-alkanes and filamentous growth in response to n-alkanes in Y. lipolytica., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Lymphoma has been reported to worsen the prognosis of COVID-19 partly because it disturbs the normal production of antibodies. We treated a man with mantle cell lymphoma treated with rituximab, who developed severe COVID-19 with viral shedding that lasted for 78 days. He stayed in the intensive care unit for 28 days and did not respond to any treatment against COVID-19. His increased oxygen demand at rest eventually resolved despite the absence of anti-SARS-CoV-2-IgG. This case illustrates that recovery from COVID-19 can occur without antibody production, and that even patients with an inability to produce antibodies can recover from severe COVID-19. It also illustrates that lymphoma patients who develop severe COVID-19 while on rituximab therapy can recover from a prolonged viral shedding state if the acute lung injury can be overcome., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study is to evaluate the risk of medial tibial cortical perforation in unicompartmental knee arthroplasty (UKA) due to peg positions on the tibial tray of the Persona Partial Knee (PPK)., Methods: Preoperative CT images of 60 patients and 60 osteoarthritic knees (30 male and 30 female patients) were used. A tibial multiplanar reconstruction (MPR) image was reconstructed in preoperative planning software, and the implant was placed in a virtual osteotomy plane. In addition to PPK, Zimmer Unicompartmental Knee (ZUK) and TRIBRID (TBD) were used for evaluation. The horizontal distances from the medial tibial cortex to the anterior and posterior pegs (APCD/PPCD, respectively) were measured under neutral, 3-degree varus, 3-degree valgus and 2 mm distal positions. The differences between implants under the same positions and between positions using the same implants were compared. The percentage of total cases with APCD/PPCD of less than 3 mm and the perforation risk rate were calculated., Results: The APCD of PPK was significantly shorter at all positions except for the varus position of TBD. The PPCD of PPK was significantly shorter at all positions compared to ZUK and TBD. There were no cases with an APCD of less than 3 mm. Except for varus positions, the perforation risk rate of PPCD was significantly higher for PPK than the other two implants., Conclusion: The posterior pegs of the PPK are located more medially than the other two implants, which may result in perforation of the medial tibial cortex during implantation. Surgeons should consider the risk involved in the type of implant used., (© 2020. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

The identification of molecular targets of bioactive food components is important to understand the mechanistic aspect of their physiological functions. Here, we have developed a screening system that enables us to determine the activation of G protein-coupled receptors (GPCRs) by food components and have identified GPR55 as a target for curcumin. Curcumin activated GPR55 and induced serum-response element- and serum-response factor-mediated transcription, which were inhibited by Rho kinase and GPR55 antagonists. Both the methoxy group and the heptadienone moiety of curcumin were required for GPR55 activation. The F190 5.47 residue of GPR55 was important for the interaction with curcumin. The curcumin-induced secretion of glucagon-like peptide-1 in GLUTag cells was inhibited by a GPR55 antagonist. These results indicate that expression screening is a useful system to identify GPCRs as targets of food components and strongly suggest that curcumin activates GPR55 as an agonist, which is involved in the physiological function of curcumin., (© 2022. The Author(s).)

By combining video laryngoscopy and fiberoptic bronchoscopy, awake intubation can be performed more safely., Competing Interests: Nothing to declare., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Objective: To evaluate the visibility of colorectal lesions using a novel image processing algorithm, texture and color enhancement imaging (TXI), that allows the acquisition of brighter images with enhanced color and surface structure., Methods: During August-September 2019, patients referred for endoscopic treatment were prospectively recruited. Electronic data acquired while observing colorectal lesions using white light imaging (WLI) were obtained and recorded: WLI, TXI mode1 (with color enhancement), and TXI mode2 (without color enhancement) videos were constructed. The lesions were also recorded using narrow-band imaging (NBI) from the same perspective as WLI. Four video clips (WLI, TXI mode1, TXI mode2, and NBI) were made per lesion. Thereafter, video files for evaluations were prepared by randomly arranging all video clips. Finally, visualization scores were evaluated by four endoscopists, and the WLI, TXI mode1, TXI mode2, and NBI results were compared., Results: Overall, 22 patients with 68 lesions were recruited; the video file for evaluation subsequently comprised 272 randomly arranged video clips. Mean visualization scores using WLI, TXI mode1, TXI mode2, and NBI were 70.0 (±20.1), 80.5 (±18.6), 75.6 (±18.1), and 69.0 (±20.6), respectively. Mean visualization scores for flat lesions using WLI, TXI mode1, TXI mode2, and NBI were 64.1 (±21.2), 76.5 (±20.18), 71.8 (±19.4), and 64.2 (±22.0), respectively. Visualization scores using TXI mode1 were significantly better than those using WLI, TXI mode2, or NBI., Conclusions: TXI enables improved visualization of colorectal lesions, even flat lesions, than WLI and NBI. TXI may allow better detection of colorectal lesions, although further prospective studies are required., Competing Interests: Kazuki Sumiyama is a Deputy Editor‐in‐Chief of DEN Open. The rest of the authors do not have any conflict of interest., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

In coronavirus disease 2019 (COVID-19), thrombus formation is related to the pathogenesis of acute respiratory distress syndrome (ARDS) and the progression of clinical symptoms. Severe damage to vascular endothelial cells and the associated cytokine storm after SARS-CoV-2 infection cause thrombogenesis and contribute to the development of more severe and unique thromboses compared to other infectious diseases. Thromboses occur more often in critically ill patients. In addition to pulmonary thromboembolism (PE) and deep vein thrombosis, acute myocardial infarction, peripheral arterial thrombosis, and aortic thrombosis have also been reported. In PE, thrombi develop in both pulmonary arteries and alveolar capillaries. These, together with intraalveolar fibrin deposition, interfere with effective gaseous exchange in the lungs and exacerbate the clinical symptoms of ARDS in patients with COVID-19. Pharmacological thromboprophylaxis is recommended for all hospitalized patients to prevent both thrombosis and aggravation of ARDS, and other organ failures. Although the pediatric population is mostly asymptomatic or develops mild disease after SARS-CoV-2 infection, a new inflammatory disorder affecting the cardiovascular system, multisystem inflammatory syndrome in children (MIS-C), has been reported. Similar to Kawasaki disease, acute myocarditis, coronary vasculitis, and aneurysms are typically seen in MISC, although these two are now considered distinct entities. A similar acute myocarditis is also observed in young male adults, in which a hyperinflammatory state after SARS-CoV-2 infection seems to be involved. Several side effects following vaccination against COVID-19 have been reported, including vaccine-induced immune thrombotic thrombocytopenia and acute myocarditis. Although these could be serious and life-threatening, the cases are very rare, thus, the benefits of immunization still outweigh the risks., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Our previous research showed that uric acid lowering therapy (ULT) for gout and hyperuricemia is being prescribed for pediatric patients even though these drugs have not been approved for use in children. However, the actual clinical situation has not been clearly elucidated. In this paper, we provide an in-depth look at the details of actual clinical practice., Methods: This retrospective cross-sectional study accessed health insurance data for 696,277 children from April 2016 through March 2017 to identify pediatric patients with gout or asymptomatic hyperuricemia, calculate the proportion of patients prescribed ULTs, and analyze population characteristics. Adherence and mean dose for febuxostat and allopurinol, the most commonly prescribed drugs, were also analyzed., Results: Among children with gout or asymptomatic hyperuricemia, we found that 35.1% (97/276) were prescribed ULT. This proportion increased with age, especially among males. By comorbidity, ULT was prescribed to 47.9% (46/96) of patients with kidney disease, 41.3% (26/63) for cardiovascular disease, 40.0% (6/15) for Down syndrome, and 27.1% (32/118) for metabolic syndrome. In patients with kidney disease, febuxostat was prescribed more than twice as frequently as allopurinol (28 vs. 12). Median values for the medication possession ratio (MPR) of febuxostat and allopurinol were 70.1 and 76.7%, respectively, and prescriptions were continued for a relatively long period for both drugs. Both drugs were prescribed at about half the adult dose for patients 6-11 years old and about the same as the adult dose for patients 12-18 years old., Conclusions: This study showed that the continuous management of serum uric acid is being explored using off-label use of ULT in pediatric patients with gout or asymptomatic hyperuricemia in Japan. Drug selection is based on patient characteristics such as sex, age, and comorbidities, and pediatric dosage is based on usage experience in adults. To develop appropriate pediatric ULT, clinical trials are needed on the efficacy and safety of ULT in the pediatric population., Trial Registration: UMIN000036029 ., (© 2021. The Author(s).)

The relationship between spinal posture and quality of life has garnered considerable attention with the increase in older community-dwelling residents. However, details of this association remain insufficient. A recent Japanese population cohort epidemiological locomotion survey (the Obuse study) revealed that the C2-C7 cervical sagittal vertical axis (CSVA) began to increase in males from their 60s, but not in females. This study aimed to clarify the pathology of these cervical spondylotic changes. A total of 411 participants (202 male and 209 female) aged between 50 and 89 years were selected by random sampling from a cooperating town's resident registry. All participants underwent lateral X-ray photography in a standing position for the measurement of several sagittal spinal alignment parameters, including CSVA, C2-C7 cervical lordosis (CL), T1 slope (T1S), and sagittal vertical axis (SVA). The presence of cervical spondylotic changes was also recorded. Associations of cervical sagittal spinal alignment with cervical spondylosis and between cervical and total sagittal spinal alignment were examined. The prevalence of cervical spondylosis was significantly higher in males (81%) than in females (70%) ( p = 0.01). CL was significantly smaller in cervical spondylosis subjects when adjusted by age (3.4 degrees less; p = 0.01). T1S minus CL displayed a moderate positive correlation with CSVA in both males and females (r = 0.49 and 0.48, respectively, both p < 0.01). In males only, CSVA and CL showed weak positive correlations with SVA (r = 0.31 and 0.22, respectively, both p < 0.01) independently of age. Cervical spinal misalignment was more clearly associated with diminished SF-8 TM scores in females than in males. In community-dwelling elderly residents, cervical sagittal spinal alignment change accompanying cervical spondylosis manifested as hypofunction to compensate for whole-spine imbalance.

Background: Blood group O of ABO blood group system is considered as a risk factor for various bleeding events, but the relationship with endoscopic treatment-associated bleeding has yet to be investigated. This study aimed to evaluate whether blood group O is associated with delayed bleeding after colorectal endoscopic resection., Methods: This was a retrospective observational study based on medical records at four university hospitals in Japan. We reviewed the records for consecutive patients who underwent colorectal endoscopic resection from January 2014 through December 2017. The primary outcome was the incidence of delayed bleeding, defined as hematochezia or melena, requiring endoscopy, transfusion, or any hemostatic intervention up to 28 days after endoscopic resection. Multivariate logistic regression analysis was performed to adjust the impact of blood group O on the delayed bleeding., Results: Among 10,253 consecutive patients who underwent colorectal endoscopic resection during the study period, 8625 patients met the criteria. In total, delayed bleeding occurred in 255 patients (2.96%). The O group had significantly more bleeding events compared with the non-O group (A, B, and AB) (relative risk, 1.62 [95% confidence interval, 1.24-2.10]; P < 0.001). In multivariate logistic regression analysis, blood group O remained an independent risk factor for the bleeding (adjusted odds ratio, 1.60 [95% confidence interval, 1.18-2.17]; P = 0.002)., Conclusions: Blood group O was associated with an increased risk of delayed bleeding in patients undergoing colorectal endoscopic resection. Preoperative screening for ABO blood group could improve risk assessments., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Sulfoquynovosylacyl propanediol (SQAP; 1) has been developed as a radiosensitizer (anti-cancer agent) for solid tumors, but it was easily cleaved in vivo and had a problem of short residence time. We synthesized a novel compound of a SQAP derivative (3-octadecanoxypropyl 6-deoxy-6-sulfo-α-d-glucopyranoside: ODSG; 2) to solve these problems not easily cleaved by lipase. ODSG (2) cytotoxicity was investigated in vitro, resulting in low toxicity like SQAP (1)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: In patients with gout, treating to target serum uric acid levels (sUA) of ≤6.0 mg/dL is universally recommended to prevent gout flare. However, there is no consensus on asymptomatic hyperuricaemia. Using Japanese health insurance claims data, we explored potential benefits of sUA control for preventing gout flare in subjects with asymptomatic hyperuricaemia., Methods: This retrospective cohort study analysed the JMDC Claims Database from April 2012 through June 2019. Subjects with sUA ≥8.0 mg/dL were identified, and disease status (prescriptions for urate-lowering therapy (ULT), occurrence of gout flare, sUA) was investigated for 1 year. Time to first onset and incidence rate of gout flare were determined by disease status subgroups for 2 years or more. The relationship between gout flare and sUA control was assessed using multivariable analysis., Results: The analysis population was 19 261 subjects who met eligibility criteria. We found fewer occurrences of gout flare, for both gout and asymptomatic hyperuricaemia, in patients who achieved sUA ≤6.0 mg/dL with ULT than in patients whose sUA remained >6.0 mg/dL or who were not receiving ULT. In particular, analysis by a Cox proportional-hazard model for time to first gout flare indicated that the HR was lowest, at 0.45 (95% CI 0.27 to 0.76), in subjects with asymptomatic hyperuricaemia on ULT (5.0

We evaluated the influences of the priming process (washing with saline), saline circulation conditions, and saline incubation on the in vitro elution of substances from three types of polysulfone (PSu) membrane dialyzers sterilized using gamma irradiation [NV-15X (Toray Industries, Inc.)], autoclaving [RENAK-PS1.6 (Kawasumi Laboratories, Inc.)], or in-line steam [FX-140J (Fresenius Medical Care)] methods as well as a non-PSu cellulose triacetate (CTA) membrane dialyzer [FB-150U(NIPRO)]. The effect of priming was evaluated by circulating 1000 mL of saline through the dialyzers at a rate of 100 mL/min and measuring the elution level of the substances by determining their ultraviolet (UV) absorption at 220 nm using spectrophotometry. All the tested dialyzers showed that the elution of the substances decreased as per the order of sample collection. Primed dialyzers were used in the subsequent experiments. Circulating saline through the primed membrane dialyzers at a flow rate of 100 mL/min caused time-dependent elution of substances from all the tested dialyzers; increasing the flow rate to 200 mL/min did not have a significant effect on the time-dependence or elution amount at each time point (0-8 h). The elution was also evaluated after incubating the membrane dialyzers with saline for 24 h. A co-submitted article (Sato et al., 2021) detailed the preparation of the identical experimental circuits, as well as the influences of saline washing, saline circulation conditions, and saline incubation on the elution of the hydrophilic agent polyvinylpyrrolidone (PVP) from each dialyzer using the Müller method, which can enable specific detection of PVP (Müller, 1968). The relative elution levels of PVP among the dialyzers and the experimental conditions were different from those of substances determined using UV (220 nm) absorption. Our data might be used for further development of experiments for identifying non-PVP substances eluted from dialyzers by providing information regarding the conditions of the elutions and types of dialyzers from which they are eluted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that have or could be perceived to have influenced the work reported in this article., (© 2021 The Author(s).)

We developed a computer-aided detection (CADe) system to detect and localize colorectal lesions by modifying You-Only-Look-Once version 3 (YOLO v3) and evaluated its performance in two different settings. The test dataset was obtained from 20 randomly selected patients who underwent endoscopic resection for 69 colorectal lesions at the Jikei University Hospital between June 2017 and February 2018. First, we evaluated the diagnostic performances using still images randomly and automatically extracted from video recordings of the entire endoscopic procedure at intervals of 5 s, without eliminating poor quality images. Second, the latency of lesion detection by the CADe system from the initial appearance of lesions was investigated by reviewing the videos. A total of 6531 images, including 662 images with a lesion, were studied in the image-based analysis. The AUC, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.983, 94.6%, 95.2%, 68.8%, 99.4%, and 95.1%, respectively. The median time for detecting colorectal lesions measured in the lesion-based analysis was 0.67 s. In conclusion, we proved that the originally developed CADe system based on YOLO v3 could accurately and instantaneously detect colorectal lesions using the test dataset obtained from videos, mitigating operator selection biases.

In hemodialysis (HD), the patient's blood is purified via circulation in an extracorporeal circuit containing a dialyzer. In the manufacturing process of polysulfone (PSu) membrane dialyzers, the membranes are hydrophilized via the addition of the hydrophilic agent polyvinylpyrrolidone (PVP) to increase their hydraulic permeability. The elution of PVP from the membrane reduces the membrane's hydraulic permeability, and the eluted PVP could cause adverse effects in the human body. Therefore, it is important to identify the factors that induce PVP elution from PSu dialyzer membranes to improve the efficiency and safety of HD. In the present study, experimental circuits connecting each of the three types of PSu membrane dialyzers that had been sterilized, using gamma irradiation, autoclaving, or in-line steam methods, were prepared. After the dialyzers were primed, saline was circulated in the circuits at a flow rate of 100 mL/min or 200 mL/min. At 0, 2, 4, 6, and 8 h after circulation was initiated, the amount of PVP eluted from the PSu membranes in vitro was determined. In this experimental setting, longer the circulation duration, greater the amount of PVP eluted from the PSu membranes of the tested dialyzers; however, the flow rate did not influence the in vitro elution of PVP. Furthermore, the immersion of the dialyzer membranes in saline for 24 h strongly facilitated the in vitro elution of PVP. In sum, these results suggest that the duration of PSu membrane incubation in saline is a determinant of the level of PVP elution from the PSu membrane dialyzers., Competing Interests: The authors declare no competing financial and non-financial interests., (© 2021 The Author(s).)

Filamentous fungi maintain hyphal growth to continually internalize membrane proteins related to cell wall synthesis, transporting them to the hyphal tips. Endocytosis mediates protein internalization via target recognition by the adaptor protein 2 complex (AP-2 complex). The AP-2 complex specifically promotes the internalization of proteins important for hyphal growth, and loss of AP-2 complex function results in abnormal hyphal growth. In this study, deletion mutants of the genes encoding the subunits of the AP-2 complex (α, β2, μ2, or σ2) in the filamentous fungus Aspergillus nidulans resulted in the formation of conidiophores with abnormal morphology, fewer conidia, and activated the cell wall integrity pathway. We also investigated the localization of ChsB, which plays pivotal roles in hyphal growth in A. nidulans, in the Δμ2 strain. Quantitative analysis suggested that the AP-2 complex is involved in ChsB internalization at subapical collar regions. The absence of the AP-2 complex reduced ChsB localization at the hyphal tips. Our findings suggest that the AP-2 complex contributes to cell wall integrity by properly localizing ChsB to the hyphal tips., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Low back pain (LBP) is one of the main etiologies of disability in daily life. In the face of LBP increases in super-aged societies, there are serious concerns of escalating medical costs and deteriorations in the social economy. It is therefore important to identify the factors associated with LBP for prompt preventative and therapeutic measures. This study investigated the prevalence of LBP and the impact of subject-specific factors on LBP development in Japanese community-dwelling older adults. We established eight groups based on age (50's, 60's, 70's, and 80's) and gender after random sampling from a resident registry. A total of 411 participants (201 male and 210 female) were enrolled for a whole-spine lateral radiographic examination and dual-energy X-ray absorptiometry. All subjects were evaluated for the presence and degree of LBP. We analyzed the impact of clinical factors on LBP using multivariate analysis. Fifty-three (12.9%) participants (23 (11.4%) male and 30 (14.3%) female) were found to have LBP. The prevalence of LBP tended to increase with age, and similar results were found between genders. In univariate analysis, the subject-related factors of the sagittal vertebral axis, pelvic incidence minus lumbar lordosis (PI-LL) mismatch, and aging had significant associations with LBP. PI-LL mismatch was a significant independent factor in multivariate analysis. In conclusion, this study identified LBP prevalence and subject-specific factors on a general population basis. Multivariate analysis revealed PI-LL mismatch as an independent factor associated with LBP in the healthy community-dwelling elderly.

Background: Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) is widely used as a patient-based evaluation tool for lumbar spine disease in Japan. However, there are currently few established JOABPEQ reference values for the general population. This study proposes population-based reference values for JOABPEQ using a randomly sampled Japanese cohort., Methods: Registered citizens of 50-89 years old were targeted for this survey. We established 8 groups based on age (50's, 60's, 70's, and 80's) and gender (male and female) after random sampling from the basic resident registry of Obuse town in 2014. A total of 414 participants (202 males and 212 females) were enrolled for calculations of average JOABPEQ scores for each age and gender group. We also evaluated for correlations between JOABPEQ domain scores and visual analogue scale (VAS) scores for low back pain., Results: Median reference JOABPEQ scores stratified by age and gender were determined in this study. Lumbar function, walking ability, and social life function deteriorated significantly with age in both genders, with remarkable declines for the social life function domain. VAS scores for low back pain were not significantly correlated with JOABPEQ item scores., Conclusions: This first resident cohort of Japanese individuals determined median JOABPEQ scores by age and gender, which might serve as reference values for future studies., Competing Interests: Declaration of competing interest The authors have no disclosure of funding received for this work., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Abstract: Recently, activities of daily living (ADL) were identified as a prognostic factor among elderly patients with heart disease; however, a specific association between ADL and prognosis after cardiac and aortic surgery is not well established. We aimed to clarify the impact of ADL capacity at discharge on prognosis in elderly patients after cardiac and aortic surgery.This retrospective cohort study included 171 elderly patients who underwent open operation for cardiovascular disease in a single center (median age: 74 years; men: 70%). We used the Barthel Index (BI) as an indicator for ADL. Patients were classified into 2 groups according to the BI at discharge, indicating a high (BI ≥ 85) or low (BI < 85) ADL status. All-cause mortality and unplanned readmission events were observed after discharge.Thirteen all-cause mortality and 44 all-cause unplanned readmission events occurred during the median follow-up of 365 days. Using Kaplan-Meier analysis, a low ADL status was determined to be significantly associated with all-cause mortality and unplanned readmission. In the multivariable Cox proportional hazard models, a low ADL status was an independent predictor of all-cause mortality and unplanned readmission after adjusting for age, sex, length of hospital stay, and other variables (including preoperative status, surgical parameter, and postoperative course).A low ADL status at discharge predicted all-cause mortality and unplanned readmission in elderly patients after cardiac and aortic surgery. A comprehensive approach from the time of admission to postdischarge to improve ADL capacity in elderly patients undergoing cardiac and aortic surgery may improve patient outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The combination of pembrolizumab and axitinib has recently been approved as a first-line treatment for previously untreated metastatic renal cell carcinoma. However, immune-related adverse events are not well known., Case Presentation: A 65-year-old male was diagnosed with renal cell carcinoma with metastases to the brain and lungs. The patient had a medical history of stasis dermatitis. During the combined treatment of pembrolizumab and axitinib, blisters appeared on the lower extremities. Skin biopsy revealed septal panniculitis, pustules, and perivascular lymphocytic and neutrophilic infiltration of the skin, and the patient was diagnosed with immune-related dermatitis. The dermatitis improved with oral prednisolone treatment., Conclusion: A case of immune-related dermatitis during combinatorial treatment with pembrolizumab and axitinib for renal cell carcinoma has been reported. Preexisting stasis dermatitis may have affected the onset and deterioration of immune-related dermatitis., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

The small GTPases RalA and RalB are members of the Ras family and activated downstream of Ras. Ral proteins are found in GTP-bound active and GDP-bound inactive forms. The activation process is executed by guanine nucleotide exchange factors, while inactivation is mediated by GTPase-activating proteins (GAPs). RalGAPs are complexes that consist of a catalytic α1 or α2 subunit together with a common β subunit. Several reports implicate the importance of Ral in pancreatic ductal adenocarcinoma (PDAC). However, there are few reports on the relationship between levels of RalGAP expression and malignancy in PDAC. We generated RalGAPβ-deficient PDAC cells by CRISPR-Cas9 genome editing to investigate how increased Ral activity affects malignant phenotypes of PDAC cells. RalGAPβ-deficient PDAC cells exhibited several-fold higher Ral activity relative to control cells. They had a high migratory and invasive capacity. The RalGAPβ-deficient cells grew more rapidly than control cells when injected subcutaneously into nude mice. When injected into the spleen, the RalGAPβ-deficient cells formed larger splenic tumors with more liver metastases, and unlike controls, they disseminated into the abdominal cavity. These results indicate that RalGAPβ deficiency in PDAC cells contributes to high activities of RalA and RalB, leading to enhanced cell migration and invasion in vitro, and tumor growth and metastasis in vivo., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: We have developed the computer-aided detection (CADe) system using an original deep learning algorithm based on a convolutional neural network for assisting endoscopists in detecting colorectal lesions during colonoscopy. The aim of this study was to clarify whether adenoma miss rate (AMR) could be reduced with CADe assistance during screening and surveillance colonoscopy., Methods: This study was a multicenter randomized controlled trial. Patients aged 40 to 80 years who were referred for colorectal screening or surveillance at four sites in Japan were randomly assigned at a 1:1 ratio to either the "standard colonoscopy (SC)-first group" or the "CADe-first group" to undergo a back-to-back tandem procedure. Tandem colonoscopies were performed on the same day for each participant by the same endoscopist in a preassigned order. All polyps detected in each pass were histopathologically diagnosed after biopsy or resection., Results: A total of 358 patients were enrolled and 179 patients were assigned to the SC-first group or CADe-first group. The AMR of the CADe-first group was significantly lower than that of the SC-first group (13.8% vs. 36.7%, P < 0.0001). Similar results were observed for the polyp miss rate (14.2% vs. 40.6%, P < 0.0001) and sessile serrated lesion miss rate (13.0% vs. 38.5%, P = 0.03). The adenoma detection rate of CADe-assisted colonoscopy was 64.5%, which was significantly higher than that of standard colonoscopy (53.6%; P = 0.036)., Conclusion: Our study results first showed a reduction in the AMR when assisting with CADe based on deep learning in a multicenter randomized controlled trial., (© 2021. Japanese Society of Gastroenterology.)

Waterfowls, such as ducks, are natural hosts of avian influenza virus (AIV) and can genetically limit the pathogenicity. On the other hand, some AIV strains cause severe pathogenicity in chickens. It is suggested that differences in the pathogenicity of AIV infection between waterfowls and chickens are related to the expression of retinoic acid-inducible gene I ( RIG-I ), a pattern recognition receptor that chickens evolutionally lack. Here, we knocked-in the duck RIG-I bearing the T2A peptide sequence at the 3' region of the Mx , an interferon-stimulated gene (ISG), in chicken embryo fibroblast cells (DF-1) using the precise integration into target chromosome (PITCh) system to control the duck RIG-I expression in chickens. The expression patterns of the duck RIG-I were then analyzed using qPCR. The knocked-in DF-1 cells expressed RIG-I via the stimulation of IFN-β and poly(I:C) in a dose-dependent manner. Moreover, poly(I:C) stimulation in the knocked-in DF-1 cells upregulated RIG-I-like receptor (RLR) family signaling pathway-related genes IFN-β, OASL, and IRF7 . The IFN-β-dependent expression of RIG-I and upregulation of IFN-β in the poly(I:C) stimulation demonstrated a positive-feedback loop via RIG-I, usually evident in ducks. Overall, this novel strategy established RIG-I-dependent immune response in chickens without overexpression of RIG-I and disruption of the host genes., (© 2021 Published by Elsevier B.V.)

Background: This study aimed to clarify how SARS-CoV-2 RNAemia is related to COVID-19 critical condition development and mortality in comparison with other predictive markers and scoring systems., Methods: This is a retrospective cohort study conducted at Yokohama Municipal Citizen's Hospital and National Institute of Infectious Diseases. We recruited adult patients with COVID-19 admitted between March 2020 and January 2021. We compared RNAemia with clinical status on admission including scoring systems such as the 4C Mortality, CURB-65, and A-DROP, as well as the Ct value of the nasopharyngeal PCR, in predicting COVID-19 mortality and critical condition development., Results: Of the 92 recruited patients (median age, 58; interquartile range, 45-71 years), 14 (14.9%) had RNAemia. These patients had an older age (median, 68 years vs. 55.5 years; p = 0.011), higher values of lactated dehydrogenase (median, 381 U/L vs. 256.5 U/L, p < 0.001), C-reactive protein (median, 10.9 mg/dL vs. 3.8 mg/dL; p < 0.001), D-dimer (median, 2.07 μg/mL vs. 1.28 μg/mL; p = 0.015), lower values of lymphocyte (median, 802/μL vs. 1007/μL, p = 0.025) and Ct of the nasopharyngeal PCR assay (median, 20.59 vs. 25.54; p = 0.021) than those without RNAemia. Univariate analysis showed RNAemia was associated with mortality (odds ratio [OR], 18.75; 95% confidence interval [CI], 3.92-89.76; area under the receiver operating characteristic curve [AUC], 0.7851; p = 0.002) and critical condition (OR, 72.00; 95% CI, 12.98-399.29; AUC, 0.8198; p < 0.001). Plus, multivariate analysis also revealed the association of RNAemia with critical condition (adjusted OR, 125.71; 95% CI, 11.47-1377.32; p < 0.001)., Conclusion: On-admission SARS-CoV-2 RNAemia is a potent predictive marker of COVID-19 critical condition and mortality. The adjusted OR for critical condition was as high as 125.71., Competing Interests: The authors have declared that no competing interests exist.

HLA-A, -C, -B, and -DRB1 genotypes were analyzed in 178 Japanese COVID-19 patients to investigate the association of HLA with severe COVID-19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA-DRB1*09:01 and severe COVID-19 (odds ratio [OR], 3.62; 95% CI, 1.57-8.35; p = 0.00251 [permutation p value = 0.0418]) when age, sex, and other common HLA alleles at the DRB1 locus were adjusted. The DRB1*09:01 allele was more significantly associated with risk for severe COVID-19 compared to preexisting medical conditions such as hypertension, diabetes, and cardiovascular diseases. These results indicate a potential role for HLA in predisposition to severe COVID-19., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pleural soft tissue density nodules with osteal protrusions are often detected at their characteristic site, the anterior portion of the rib tubercle. Herein, we report a pathologically proven case of this lesion. A 65-year-old man underwent surgery for primary lung cancer in the right middle lobe. Preoperative computed tomography showed a 10-mm pleural soft tissue density nodule with osteal protrusion anterior to the tubercle of the right sixth rib, and this lesion was concomitantly resected. Intraoperative findings showed that this pleural lesion originated from the parietal pleura and was pathologically diagnosed as a benign fibrous tissue. We can avoid unnecessary invasive examinations such as biopsies by recognizing these benign fibrous lesions., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Esophageal ectopic sebaceous glands are very rare lesions. A series of 5 cases in a single report has been the maximum number described in the English literature to date. We conducted a clinicopathologic study of 8 cases of esophageal ectopic sebaceous glands. The median patient age at the time of diagnosis was 60 years (range, 50-71 years), and 7 of the 8 patients were male. A focal lesion was observed in 7 cases, whereas 1 case exhibited multiple lesions throughout the esophagus. Four patients had previously undergone upper gastrointestinal endoscopy; in 3 patients, the focal lesion had not been detected. After diagnosis, 3 cases showed spontaneous regression at least once. Immunohistochemically, sebocytes of all 8 cases were negative for the estrogen receptor (ER) and the progesterone receptor (PgR), whereas sebocytes of 5 cases were positive for the androgen receptor (AR). Basal/parabasal cells were positive for AR, ER, and PgR in 5, 7, and 4 cases, respectively. GATA3 was expressed in the sebocytes and basal/parabasal cells of 6 out of 7 available cases, whereas all of 7 available cases were negative for mammaglobin and GCDFP15. Our report provides the basic clinicopathologic characteristics of esophageal ectopic sebaceous glands by the largest case series reported in English literature to date. Furthermore, the chronological changes, particularly spontaneous regression, and immunohistochemical expression of hormone receptors and GATA3 are compatible with lesions resulting from congenital misplacement under hormonal regulation. Therefore, they seem to be congenital misplacements detectable as a result of hormonal stimulated growth.

Chronic blood trauma caused by the shear stresses generated by mechanical circulatory support (MCS) systems is one of the major concerns to be considered during the development of ventricular assist devices. Large multimers with high-molecular-weight von Willebrand factor (VWF) are extended by the fluid forces in a shear flow and are cleaved by ADAMTS13. Since the mechanical revolving motions in artificial MCSs induce cleavage in large VWF multimers, nonsurgical bleeding associated with the MCS is likely to occur after mechanical hemodynamic support. In this study, the shear stress (~ 600 Pa) and exposure time related to hemolysis and VWF degradation were investigated using a newly designed mechanical shuttle shear flow tester. The device consisted of a pair of cylinders facing the test section of a small-sized pipe; both the cylinders were connected to composite mechanical heads with a sliding-sleeve structure for axial separation during the withdrawing motion. The influence of exposure time, in terms of the number of stress cycles, on hemolysis and VWF degradation was confirmed using fresh goat blood, and the differences in the rates of dissipation of the multimers were established. The plasma-free hemoglobin levels showed a logarithmic increase corresponding to the number of cycles, and the dissipation of large VWF multimers occurred within a few seconds under high shear stress flow conditions.

Koji molds, such as Aspergillus oryzae and Aspergillus sojae, are used in the food industry in East Asia and have been explored for the large-scale production of extracellular hydrolases. We previously found that the deletion of a gene encoding a putative GT2 glycosyltransferase increased production of extracellular hydrolases in A. sojae. The gene was named rseA (regulator of the secretory enzyme A). We predicted that intracellular signaling pathways were involved in the increased production of hydrolases in the ΔrseA mutant of A. sojae. However, little has been reported on molecular biological knowledge about A. sojae. Hence, Aspergillus nidulans, a typical model organism used in molecular biology, was employed for the functional characterization of rseA in this study. Deletion of the rseA ortholog in A. nidulans induced increased extracellular production of hydrolases under the solid-state cultivation condition, similar to that in A. sojae. The involvement of the cell wall integrity pathway and the high osmolarity glycerol pathway in ΔrseA was further investigated. The results indicated that the HOG pathway played an important role in the increased extracellular production of hydrolases caused by the deletion of the rseA gene. rseA ortholog in A. nidulans was identical to cpsA, which was reported to function as a regulator of mycotoxin production, morphogenesis, and cell wall biosynthesis. However, this is the first study reporting that rseA/cpsA regulates extracellular hydrolase production in A. nidulans., (Copyright © 2021 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to verify the effects of a new remnant augmentation technique with anatomical double-bundle anterior cruciate ligament (ACL) reconstruction for postoperative clinical scores, anterior stability and frequency of complications compared to remnant removal and cases with remnant defects., Methods: The 105 patients who underwent anatomical double-bundle ACL reconstruction were divided into three groups. If the remnant was a Crain I-III type, remnant-preserving bone tunnel creation was attempted. After the creation of the bone tunnel, good continuity was maintained in 34 patients (preserved group). Due to lost continuity, the remnant was resected in 26 patients (resected group). No identifiable remnant continuity remained (Crain IV) in 45 patients (absent group). The Lysholm knee score, Tegner activity scale, International Knee Documentation Committee (IKDC) subjective score, anterior stability measured using the KT-1000 arthrometer at 2 years postoperatively, and frequency of complications were compared among the three groups. Univariate and multiple linear regression analysis were performed to clarify the factors affecting postoperative anterior stability., Results: The Lysholm knee score, Tegner activity scale, IKDC subjective score, and frequency of complications were not significantly different among the groups. The mean side-to-side difference of anterior stability was significantly better in the preserved group (0.3 ± 1.6 mm) compared to the resected group (1.6 ± 2.3 mm, p = 0.003) and absent group (1.6 mm ± 1.7, p = 0.009). The multiple linear regression analysis showed remnant preservation significantly related to postoperative anterior stability., Conclusion: Although there were no differences in clinical scores, the ACL reconstruction with new preservation technique showed good anterior stability and no difference in the frequency of complications., Competing Interests: The authors have no conflict of interests to declare., (© 2021 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Polytetrafluoroethylene (PTFE) fine powder with 93% crystallinity was irradiated by an electron beam (EB) at various temperatures under a nitrogen atmosphere. Trapped free radicals in PTFE were studied using electron spin resonance (ESR) spectroscopy. The observed spectra of the samples exposed to air after irradiation at various temperatures showed asymmetrical signals, which are middle-chain type peroxide macroradicals derived from fluoroalkyl radicals. The radical yields at each irradiation temperature increased with increasing absorbed dose, and eventually saturated. The higher irradiation temperature resulted in higher radical yields when compared at the same exposed dose. Furthermore, the G-value of the radicals (G(R·)) increases with increasing irradiation temperatures corresponding to each relaxation and transition temperature. It is concluded that the chain reaction by the fluorine extraction from the main chain due to the end-chain radical generated via β-scission after dissociative electron attachment (DEA) is enhanced by the synergistic effect of heat and radiation.

Extensive activation of glial cells during a latent period has been well documented in various animal models of epilepsy. However, it remains unclear whether activated glial cells contribute to epileptogenesis, i.e., the chronically persistent process leading to epilepsy. Particularly, it is not clear whether interglial communication between different types of glial cells contributes to epileptogenesis, because past literature has mainly focused on one type of glial cell. Here, we show that temporally distinct activation profiles of microglia and astrocytes collaboratively contributed to epileptogenesis in a drug-induced status epilepticus model. We found that reactive microglia appeared first, followed by reactive astrocytes and increased susceptibility to seizures. Reactive astrocytes exhibited larger Ca2+ signals mediated by IP3R2, whereas deletion of this type of Ca2+ signaling reduced seizure susceptibility after status epilepticus. Immediate, but not late, pharmacological inhibition of microglial activation prevented subsequent reactive astrocytes, aberrant astrocyte Ca2+ signaling, and the enhanced seizure susceptibility. These findings indicate that the sequential activation of glial cells constituted a cause of epileptogenesis after status epilepticus. Thus, our findings suggest that the therapeutic target to prevent epilepsy after status epilepticus should be shifted from microglia (early phase) to astrocytes (late phase).

Osteoporosis may increase fracture risk and reduce healthy quality of life in older adults. This study aimed to identify an assessment method using physical performance tests to screen for osteoporosis in community dwelling individuals. A total of 168 women aged 50-89 years without diagnosed osteoporosis were randomly selected from the resident registry of a cooperating town for the evaluation of physical characteristics, muscle strength, and several physical performance tests. The most effective combinations of evaluation items to detect osteoporosis (i.e., T-score ≤ -2.5 at the spine or hip) were selected by multivariate analysis and cutoff values were determined by likelihood ratio matrices. Thirty-six women (21.4%) were classified as having osteoporosis. By analyzing combinations of two-step test (TST) score and body mass index (BMI), osteoporosis could be reliably suspected in individuals with TST ≤ 1.30 and BMI ≤ 23.4, TST ≤ 1.32 and BMI ≤ 22.4, TST ≤ 1.34 and BMI ≤ 21.6, or TST < 1.24 and any BMI. Setting cut-off values for TST in combination with BMI represents an easy and possibly effective screening tool for osteoporosis detection in resident health exams.

Ykt6 is an evolutionarily conserved SNARE protein regulating Golgi membrane fusion and other diverse membrane trafficking pathways. Unlike most SNARE proteins, Ykt6 lacks a transmembrane domain but instead has a tandem cysteine motif at the C-terminus. Recently, we have demonstrated that Ykt6 undergoes double prenylation at the C-terminal two cysteines first by farnesyltransferase and then by a newly identified protein prenyltransferase named geranylgeranyltransferase type-III (GGTase-III). GGTase-III consists of a novel α subunit prenyltransferase alpha subunit repeat containing 1 (PTAR1) and the β subunit of Rab geranylgeranyltransferase. PTAR1 knockout (KO) cells, where Ykt6 is singly prenylated with a farnesyl moiety, exhibit structural and functional abnormalities in the Golgi apparatus with delayed intra-Golgi trafficking and impaired protein glycosylation. It remains unclear whether the second prenylation of Ykt6 is required for proper trafficking of lysosomal hydrolases from Golgi to lysosomes. Here, we show that lysosomal hydrolases, cathepsin D and β-hexosaminidase, were missorted at the trans-Golgi network and secreted into the extracellular space in PTAR1 KO cells. Moreover, maturation of these hydrolases was disturbed. LC3B, an autophagy marker, was accumulated in PTAR1 KO cells, suggesting defects in cellular degradation pathways. Thus, doubly prenylated Ykt6, but not singly prenylated Ykt6, is critical for the efficient sorting and trafficking of acid hydrolases to lysosomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

The yeast Yarrowia lipolytica assimilates hydrophobic compounds, such as n-alkanes and fatty acids, as sole carbon and energy sources. It has been shown that the acyl-CoA synthetase (ACS) genes, FAT1 and FAA1, are involved in the activation of fatty acids produced during the metabolism of n-alkanes, but the ACS genes that are involved in the metabolism of fatty acids from the culture medium remains to be identified. In this paper, we have identified the ACS genes involved in the utilization of exogenous fatty acids. RNA-seq analysis and qRT-PCR revealed that the transcript levels of the peroxisomal ACS-like protein-encoding genes AAL4 and AAL7 were increased in the presence of oleic acid. The single deletion mutant of AAL4 or AAL7 and double deletion mutant of AAL4 and AAL7 did not show any defects in the growth on the medium containing glucose, glycerol, n-alkanes, or fatty acids. In contrast, the mutant with deletion of seven genes, FAA1, FAT1-FAT4, AAL4, and AAL7, showed severe growth defects on the medium containing dodecanoic acid or oleic acid. These results suggest that Aal4p and Aal7p play important roles in the metabolism of exogenous fatty acids in collaboration with Faa1p and Fat1p-Fat4p.

A questionnaire on COVID-19-related thrombosis in patients hospitalized before Aug 31, 2020, was sent to 399 hospitals throughout Japan. Responses were received from 111 (27.8%) with information on 6,202 COVID-19 patients. Of these, 333 and 56 required ventilation or extracorporeal membrane oxygenation (ECMO), respectively, and 212 died (3.4%). D-dimer levels were measured in 75.0% of the patients, revealing that 9.2% and 7.6% exhibited D-dimer increases of 3-8-fold and ≥8-fold the reference value, respectively. Thrombotic events occurred in 108 patients (1.86% of the 5,807 patients with available data) including symptomatic cerebral infarction in 24, myocardial infarction in 7, deep vein thrombosis in 41, pulmonary thromboembolism in 30, and other thrombotic events in 22. Some patients developed multiple thrombotic events. Thrombosis occurred in 32 patients with mild or moderate COVID-19 severity (0.59% of those with data available) and in 52 patients on ventilation or ECMO (13.5% of severe patients for whom data were available). Thrombosis occurred in 67 patients during worsening clinical condition and in 26 during recovery. Anticoagulant therapy was provided to 893 patients (14.6% of the 6,119 patients with available data), the main reasons being provided as elevated D-dimer levels and worsening clinical condition.

An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19). However, data regarding myeloid cell expansion have been collected in Europe, where the mortality rate by COVID-19 is greater than those in other regions including Japan. Thus, characteristics of COVID-19-induced myeloid cell subsets remain largely unknown in the regions with low mortality rates. Here, we analyzed cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis, using blood samples from Japanese COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, but not other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Contrary to previous studies in Europe, this subset selectively expanded in survivors of severe cases and subsided before discharge, but such transient expansion was not observed in non-survivors in Japanese cohort. Analysis of plasma cytokine/chemokine levels revealed positive correlation of PMN-MDSC frequencies with IL-8 levels, indicating the involvement of IL-8 on recruitment of PMN-MDSCs to peripheral blood following the onset of severe COVID-19. Our data indicate that transient expansion of the PMN-MDSC subset results in improved clinical outcome. Thus, this myeloid cell subset may be a predictor of prognosis in cases of severe COVID-19 in Japan., (© The Japanese Society for Immunology. 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Interleukin-19 (IL-19) acts as a negative-feedback regulator to limit proinflammatory response of macrophages and microglia in autocrine/paracrine manners in various inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system (CNS), but it remains uncertain how IL-19 contributes to MS pathogenesis. Here, we demonstrate that IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by promoting IL-17-producing helper T cell (Th17 cell) infiltration into the CNS. In addition, IL-19-deficient splenic macrophages expressed elevated levels of major histocompatibility complex (MHC) class II, co-stimulatory molecules, and Th17 cell differentiation-associated cytokines such as IL-1β, IL-6, IL-23, TGF-β1, and TNF-α. These observations indicated that IL-19 plays a critical role in suppression of MS pathogenesis by inhibiting macrophage antigen presentation, Th17 cell expansion, and subsequent inflammatory responses. Furthermore, treatment with IL-19 significantly abrogated EAE. Our data suggest that IL-19 could provide significant therapeutic benefits in patients with MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Horiuchi, Parajuli, Komiya, Ogawa, Jin, Takahashi, Azuma, Tanaka, Suzumura and Takeuchi.)

Purpose: This study assessed factors associated with achieving target serum uric acid (sUA) level and occurrence of gouty arthritis in Japanese clinical practice., Methods: Japanese health insurance claims and medical check-up data from October 2015 to March 2017 were analyzed to assess factors associated with target sUA achievement in gout and asymptomatic hyperuricemia and gouty arthritis in gout. Target sUA was further assessed by subgroup analysis of urate-lowering therapy (ULT) prescriptions and outcomes, stratified by renal function., Results: Patients achieving target sUA tended toward older, female, higher ULT dose, higher adherence, more comorbidities, and/or antidiabetic drugs prescribed. Renal dysfunction and/or diuretic prescriptions were associated with reduced achievement of target sUA. Severe renal dysfunction was particularly influential (odds ratio [OR] = 0.22 [95% confidence interval (CI): 0.10-0.48] for <15, 0.15 [0.10-0.23] for ≥15 to <30, compared with eGFR ≥90 mL/min/1.73 m 2 ). Across all renal function categories, mean prescribed ULT dose was low (febuxostat 17.0-21.0 mg/day, allopurinol 123.1-139.6 mg/day), and target sUA achievement was reduced among renal dysfunction patients. Gouty arthritis was more likely in patients with a prior history of such occurrences, and less likely for higher ULT adherence, sUA monitored regularly at medical facilities, and/or more comorbidities., Conclusion: In a real-world setting, severe renal dysfunction is the most important risk factor for failure to achieve the target sUA, suggesting suboptimal disease management in patients with gout or hyperuricemia complicated by this condition. Findings associated with gouty arthritis suggest that these occurrences could be successfully managed by regular monitoring of sUA and closer adherence to ULT., (© 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Phosphatidylserine decarboxylases (PSDs) catalyze the production of phosphatidylethanolamine (PE) from phosphatidylserine (PS) and are crucial for the maintenance of PE levels in fungi. The PSDs are classified into two types; the type I PSDs are conserved from bacteria to humans, while the type II PSDs exist only in fungi and plants. In yeasts, the deletion of type I PSD-encoding genes causes severe growth retardation. In contrast, the deletion of type II PSD-encoding genes has little or no effect. In this study, we found four genes encoding type II PSD orthologs in the filamentous fungus Aspergillus nidulans; these included psdB, psdC, psdD, and psdE. Deletion of psdB caused severe growth defects on minimal medium and these defects were partially restored by the addition of ethanolamine, choline, PE, or phosphatidylcholine into the medium. The conidiation efficiency of the psdB deletion mutant was dramatically decreased and its conidiophore structures were aberrant. In the psdB deletion mutant, the PE content decreased while the PS content increased. We further showed that PsdB had a major PSD activity. Our findings suggest that the type II PSDs exert important roles in the phospholipid homeostasis, and in the growth and morphogenesis of filamentous fungi., (Copyright © 2020 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Abstract: No guidelines have been established for the evaluation of swallowing function following extubation. The factors of bedside swallowing evaluations (BSEs) that are associated with the development of pneumonia have not been fully elucidated. This study aimed to retrospectively investigate the most appropriate measurements of BSEs for predicting pneumonia.The study subjects were 97 adults who underwent BSEs following cardiovascular surgery. Patients were divided into the pneumonia onset group (n = 21) and the non-onset group (n = 76). Patient characteristics, intraoperative characteristics, complications, BSE results, and postoperative progress were compared between the groups. BSEs were composed of consciousness level, modified water swallowing test (MWST) score, repetitive saliva swallowing test score, speech intelligibility score, and risk of dysphagia in the cardiac surgery score. Univariate and multivariate analyses with the BSE as the independent variable and pneumonia onset as the dependent variable were also performed to identify factors that predict pneumonia. For factors that became significant in univariate analysis, the incidence of pneumonia was shown using the Kaplan-Meier curve.No significant differences were found in patient characteristics, intraoperative characteristics, and complications between the 2 groups. The postoperative progress was significantly different between the 2 groups, the pneumonia-onset group had a significantly longer time until the start of oral intake and a significantly lower median value of Food Intake Level Scale at the time of discharge. According to univariate and multivariate analyses, MWST score was a significant factor for predicting the onset of pneumonia even after adjusting for patient characteristics and surgical factors, and the incidence of pneumonia increased approximately 3 times when the MWST score was 3 points or less.The MWST score after extubation in cardiovascular surgery was the strongest predictor of postoperative pneumonia in BSEs. Furthermore, the incidence of pneumonia increased approximately 3 times when the MWST score was 3 points or less. Predicting cases with a high risk of developing pneumonia allows nurses and attending physicians to monitor the progress carefully and take aggressive preventive measures., Competing Interests: The authors have no conflicts of interest to disclose, (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To assess gout and asymptomatic hyperuricemia in Japan and review treatment conditions., Methods: This retrospective cross-sectional study analyzed the prevalence of hyperuricemia and gout, and characteristics and treatment of patients with those conditions, using Japanese health insurance claims and medical check-up data collected from April 2016 through March 2017., Results: Among 2,531,383 persons registered in the database, 1.1% (men 1.9%, women <0.1%) were diagnosed with gout and 2.6% (4.1%, 0.4%) with asymptomatic hyperuricemia. Medical check-ups showed 13.4% (19.6%, 1.0%) of patients with hyperuricemia (serum uric acid [sUA] > 7.0 mg/dL). Urate-lowering therapy (ULT) was prescribed for 80.7% of patients identified with gout and 72.4% identified with asymptomatic hyperuricemia. ULT adherence was satisfactory, but most patients were treated with low-dose ULT. Less than half of patients receiving ULT achieved the sUA target (≤6.0 mg/dL). In gout patients, the incidence of gout flare was 47.8% (0.74 flares/person-year)., Conclusions: Although hyperuricemia prevalence is similar in Japan and worldwide, gout is comparatively rare in Japan. Gout and asymptomatic hyperuricemia are often treated with low-dose ULT, and many patients fail to reach target sUA, suggesting that gout management is suboptimal in Japan. Patients would benefit from stricter focus on a treat-to-target approach for gout management.

Contrast medium-enhanced computed tomography revealed a mass in the liver of a 65-year-old man. The edge but not the center of the mass was enhanced. Ultrasonography-guided percutaneous needle biopsy revealed the diagnosis of angiosarcoma of the liver, and it was treated with chemotherapy. Angiosarcoma of the liver has various appearances on imaging and is not often diagnosed while patients are alive. If the tumor is difficult to diagnose by imaging and thought to be unresectable, a biopsy can help in guiding treatment, but treatment should be adapted with caution.

Background: To determine normative values for the QuickDASH questionnaire in the elderly Japanese population and their associated factors. Methods: Three-hundred and eighty-one residents between 50 and 89 years of age were randomly selected from residents of a town in Japan. All participants completed a QuickDASH questionnaire. A multivariate analysis was performed to identify associated factors. Results: Males and females aged 70-79 and 80-89 showed significantly higher QuickDASH scores than the 50-59 age groups. Females aged 50 to 59 showed significantly higher QuickDASH scores than males aged 50-59. Motion pain or tenderness at the shoulder and side pinch strength showed a significant effect on QuickDASH scores. Conclusions: The mean QuickDASH score was 5.7. As an associated factor for the QuickDASH, aging, female, and shoulder disorders were confirmed.