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Accurately identifying neoantigens is crucial for developing effective cancer vaccines and improving tumor immunotherapy. Mass spectrometry-based immunopeptidomics has emerged as a promising approach to identifying human leukocyte antigen (HLA) peptides presented on the surface of cancer cells, but false-positive identifications remain a significant challenge. In this study, liquid chromatography-tandem mass spectrometry-based proteomics and next-generation sequencing were utilized to identify HLA-presenting neoantigenic peptides resulting from non-synonymous single nucleotide variations in tumor tissues from 18 patients with renal cell carcinoma or pancreatic cancer. Machine learning was utilized to evaluate Mascot identifications through the prediction of MS/MS spectral consistency, and four descriptors for each candidate sequence: the max Mascot ion score, predicted HLA binding affinity, aliphatic index and retention time deviation, were selected as important features in filtering out identifications with inadequate fragmentation consistency. This suggests that incorporating rescoring filters based on peptide physicochemical characteristics could enhance the identification rate of MS-based immunopeptidomics compared to the traditional Mascot approach predominantly used for proteomics, indicating the potential for optimizing neoantigen identification pipelines as well as clinical applications.

Background/purpose: Cognitive flexibility is a personality trait, which can influence how effectively a healthcare professional can manage a challenging clinical situation. This study explored the cognitive flexibility of undergraduate dental hygiene students at two universities in Asia to gather baseline information in order to consider whether there was an educational need for pre-clinical students with regards to this personality factor. Materials and methods: Participants were all undergraduate dental hygiene students in the 2022 academic year at Tokyo Medical and Dental University (TMDU; n = 79) and Taipei Medical University (TMU; n = 88). An anonymous questionnaire was distributed, which included questions on demographic information and the Cognitive Flexibility Inventory (CFI). Results: The response rates were 97.5% (TMDU) and 89.8% (TMU). The CFI total scores were 91.77 for TMDU and 95.87 for TMU, and there was no significant difference between the two schools. The Alternatives scores were significantly higher in TMU than TMDU (P = 0.044), but there were no significant differences in the Control scores between the two schools. There were also no significant differences between school years of both universities. Conclusion: The dental hygiene students from both dental schools exhibit moderate cognitive flexibility. The educators in both dental schools may consider whether they should investigate and develop this personality factor further during the undergraduate training of their dental hygiene students.

The synthesis of cellulose oligomers catalyzed by cellodextrin phosphorylase (CDP) can easily yield microcrystals with functional groups exposed on their surfaces using glucose derivatives with various functional groups at the C1 position as primers. In this study, we examined and compared the effects of primers with various structures on the structural characteristics of the resulting synthetic products. The yield of the synthetic products positively correlated with the CDP activity toward the primer, whereas the degree of polymerization (DP) and molecular weight distribution showed an inverse correlation. However, deviations from these trends were observed, suggesting the influence of varying solubilities and crystallization behaviors due to the introduction of functional groups. The obtained microcrystals exhibited a primarily plate-like shape with a thickness increasing in proportion to the DP, resulting in larger plate-like crystals at higher DP values. These findings provide insights into strategies for controlling the structure of the resulting cellulose oligomers.

Phase angle (PhA) has garnered increasing attention; however, its relationship with cognitive function has not been fully elucidated. This cross-sectional study explores the relationship between PhA using bioelectrical impedance analysis, and cognitive function among older adults with cognitive impairment in Japan, ranging from subjective cognitive decline to Alzheimer's disease. We hypothesized that lower PhA values, correlates with greater cognitive decline. To test this, we analyzed data from 726 cognitively impaired patients, focusing on variables such as PhA, walking speed, and cognitive assessments including the Mini-Mental State Examination. The results show that higher PhA values are significantly associated with improved cognitive performance, and no significant ''gender × PhA'' interaction was detected in the overall sample.

Notwithstanding the obvious interconnection between humans and the world that they share with non-human inhabitants, the impact of our changing climate on certain aspects of the public health ecosystem has been under-investigated. We briefly describe some of the possible climate-induced changes in the procurement, distribution, access and use of medications, including those for animals generally and livestock specifically. A fuller understanding of the effect of climate change on medicine supply, access, use and quality, including how these affect antimicrobial resistance, would contribute to the further development of the “One Health” and “One Health Systems” concepts. We suggest that this understanding is not yet available, even though the changing incidence of infectious diseases due to changing climate has been studied. There is a need for improved understanding of the impact of extremes of humidity and heat on medication quality and research into heat-stable medicines as well as strategies for the improving resilience of the pharmaceutical supply and distribution system in complex public health emergencies caused by aberrant weather patterns.

Background: Chickens are an important source of animal protein, nutrition, and income in many low- and middle-income countries (LMICs). They are also a major reservoir of enteropathogens that contribute to the burden of illnesses among children. Food systems present a risk for transmission of enteropathogens from poultry to humans, but there is a lack of population-level data on the pattern of purchase, ownership, and consumption of live chickens and their products in LMICs to better characterize that risk. Methods: To assess chicken purchase, ownership, and consumption practices, we conducted a population-based survey using a structured questionnaire in Maputo, Mozambique in 2021. Multi-stage cluster sampling was used to obtain a representative sample of households in our study area. To minimize sampling bias and ensure a representative sample, we applied survey weighting using district-level population data and estimated weighted population-level values. Results: Heads of 570 households in Maputo completed our survey. Approximately half of these households purchased broiler chicken meat (weighted percentage of households: 44.8 %) and eggs (46.5 %) in the previous week of the survey date, while indigenous chicken meat was less popular (1950, 1.1 %). The most common source of chicken products was corner stores (i.e., small convenience shops on streets), followed by wet markets. Live chickens were raised by 15.6 % of households, and chicken feces were observed on the floor or ground at the majority of these households during house visits. Discussion: Our findings suggest that poultry provides a major source of animal protein in this setting. Given the predicted growth of poultry farming in LMICs in the coming decades, implementing One Health-based food safety measures at primary sources of chicken products, such as corner stores and wet markets, will be critical to controlling zoonotic pathogen transmission risks.

Summary: Background: Emergence of SARS-CoV-2 variants that escape neutralising antibodies hampers the development of vaccines and therapeutic antibodies against SARS-CoV-2. IGHV3-53/3-66-derived public antibodies, which are generally specific to the prototype virus and are frequently induced in infected or vaccinated individuals, show minimal affinity maturation and high potency against prototype SARS-CoV-2. Methods: Monoclonal antibodies isolated from a Delta breakthrough infection case were analysed for cross-neutralising activities against SARS-CoV-2 variants. The broadly neutralising antibody K4-66 was further analysed in a hamster model, and the effect of somatic hypermutations was assessed using the inferred germline precursor. Findings: Antibodies derived from IGHV3-53/3-66 showed broader neutralising activity than antibodies derived from IGHV1-69 and other IGHV genes. IGHV3-53/3-66 antibodies neutralised the Delta variant better than the IGHV1-69 antibodies, suggesting that the IGHV3-53/3-66 antibodies were further maturated by Delta breakthrough infection. One IGHV3-53/3-66 antibody, K4-66, neutralised all Omicron subvariants tested, including EG.5.1, BA.2.86, and JN.1, and decreased the viral load in the lungs of hamsters infected with Omicron subvariant XBB.1.5. The importance of somatic hypermutations was demonstrated by the loss of neutralising activity of the inferred germline precursor of K4-66 against Beta and Omicron variants. Interpretation: Broadly neutralising IGHV3-53/3-66 antibodies have potential as a target for the development of effective vaccines and therapeutic antibodies against newly emerging SARS-CoV-2 variants. Funding: This work was supported by grants from AMED (JP23ym0126048, JP22ym0126048, JP21ym0126048, JP23wm0125002, JP233fa627001, JP223fa627009, JP24jf0126002, and JP22fk0108572), and the JSPS (JP21H02970, JK23K20041, and JPJSCCA20240006).

Background/purpose: The number of middle-aged and elderly orthodontic patients is increasing due to changes in age composition. It is important to investigate the detailed mechanisms of bone remodeling in orthodontic tooth movement (OTM) in the elderly. However, there are few reports on the mechanism of tooth movement in the elderly. The purpose of the present study was to analyze OTM and osteoclastogenesis in aged mice and to elucidate the mechanism. Materials and methods: It has been reported that tumor necrosis factor (TNF)-α plays an important role in osteoclast formation and OTM. First, 8-week-old and 78-week-old male C57BL/6J mice were subcutaneously injected with TNF-α into the calvaiae, and micro-CT, tartrate-resistant acid phosphatase (TRAP) staining, and real-time PCR were performed to evaluate osteoclast formation and bone resorption. Furthermore, osteoclastogenesis by TNF-α and receptor activator of nuclear factor-kappa B ligand (RANKL) using bone marrow cells was evaluated in vitro. Finally, a nickel-titanium closed-coil spring was attached, mesial movement of the maxillary left first molar was performed, and tooth movement distance and osteoclast formation were evaluated. Results: Compared to 8-week-old mice, 78-week-old mice had decreased TNF-α-induced bone resorption, osteoclastogenesis, and TRAP and cathepsin K expression in the calvariae. In vitro osteoclast formation also decreased in 78-week-old mice. Furthermore, tooth movement distance and osteoclastogenesis were reduced. Conclusion: OTM decreased in aged mice, which was shown to be caused by a decrease in osteoclastogenesis. Therefore, it was suggested that it is necessary to keep in mind that tooth movement may be suppressed when treating elderly patients.

Pakistan is the fifth most populous country in the world. Its ecological environment is facing numerous stresses such as climate change, rapid urbanization, natural disasters, and a decline in air quality. Thus, the scientific understanding of spatial and temporal changes in Pakistan's ecological environment is crucial for formulating an informed strategy for regional sustainability. This study used the Google Earth Engine platform and the Remote Sensing Ecological Index (RSEI) to investigate ecological vulnerability in three provinces of Pakistan for 1990, 2000, 2010, and 2020. Landsat 5 and Landsat 8 datasets are used to construct RSEI indicators and Principal Component Analysis (PCA) is adopted to objectively compute RSEI for the past three decades. The results indicated that (1) the ecological vulnerability of the Punjab province exhibited a slightly improved trend from 1990 to 2020 with overall dominance of ‘moderate’ level vulnerability in all four years; (2) The Sindh province has exhibited a declining trend of the ecological environment with ‘poor’ ecological vulnerability contributing to 28.6% of the total area in 2020 as compared to 1.04% of the total area in 1990; and (3) The ecological environment of Balochistan province has shown resilience to some extent during 1900–2010 with the dominance of a ‘moderate’ level of ecological vulnerability. However, a decline is observed between 2010 and 2020. These research results can provide support for the Punjab, Sindh, and Balochistan provinces in achieving sustainable development while conserving the regional ecological environment.

Background: Evaluating the selective pressure of antimicrobials on bacteria is important for promoting antimicrobial stewardship programs (ASPs). The aim of this study was to assess the selective pressure of antimicrobials by evaluating their use (carbapenem [CBP] and CBP-sparing therapy) over time and the detection status of CBP-resistant organisms using multicenter data. Methods: Among the facilities whose data were registered in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology from 2017 to 2020, those that had data on the use of CBP and CBP-sparing therapy (fluoroquinolones [FQs], cefmetazole [CMZ], piperacillin–tazobactam [PIP/TAZ], ampicillin–sulbactam [ABPC/SBT], ceftriaxone/cefotaxime [CTRX/CTX], CAZ (ceftazidime), cefepime [CFPM], and aminoglycosides [AGs]) as well as on CBP-resistant Enterobacterales (CRE) and CBP-resistant Pseudomonas aeruginosa (CRPA) detection were included. Alcohol-based hand rubbing (ABHR) usage was also analyzed. Regression analyses, including multivariable regression analysis, were performed to evaluate trends. The association of antimicrobial use density (AUD) with CRE and CRPA detection rates was evaluated. Results: In 28 facilities nationwide, CBP, FQ, CAZ, AG, and PIP/TAZ use decreased over the 3-year period, whereas the use of CMZ, ABPC/SBT, CTRX/CTX, CFPM, and ABHR as well as the rates of CRE and CRPA detection increased. The average AUD did not significantly correlate with CRE and CRPA detection rates. The multivariable regression analysis did not reveal any significant correlation between each AUD or ABHR and CRE or CRPA detection. Conclusion: CBP and ABHR use showed a decreasing and an increasing trend, respectively, while CRPA and CRE detection rates exhibited a gradual increase. The considerably low CRE and CRPA detection rates suggest that slight differences in numbers may have been observed as excessive trend changes. Further investigation is warranted to evaluate selective pressure while considering the characteristics of ASP and the mechanisms underlying resistance.

Background: The KIT receptor tyrosine kinase and its ligand, stem cell factor (SCF), control proliferation and survival of mast cells. Thus, targeting KIT signaling may show promise for the treatment of allergic diseases involving mast cells. Recently, we discovered a new compound, MOD000001, as a potential small-molecule KIT kinase inhibitor by using an in silico approach. Objective: We sought to determine whether MOD000001 is highly selective to KIT, inhibits KIT signaling in mast cells, and affects IgE-mediated mast cell activation. Methods: The interaction of MOD000001 with 468 human kinases and its inhibitory activity against KIT were profiled and evaluated by using KINOMEscan (Discover X/Eurofins Corporation, Fremont, Calif) and cell-free kinase assays, respectively. The effects of MOD000001 on SCF-dependent signaling were examined by using primary mouse and human mast cells. The effects of MOD000001 on SCF-induced degranulation and passive cutaneous anaphylaxis reaction were examined in mice. Results: MOD000001 interacted with KIT and inhibited KIT kinase activity with high selectivity. MOD000001 suppressed SCF-induced KIT signaling in mouse and human mast cells and in mice. Passive cutaneous anaphylaxis reaction was suppressed in mice treated with MOD000001 both for a short-term (1 week) and for a long-term (7 weeks). Mice treated with MOD000001 for a long-term, but not for a short-term, showed skin mast cell reduction. Conclusions: MOD000001 is a highly selective KIT inhibitor that can suppress IgE-mediated mast cell activation in vivo. MOD000001 may do so by reducing tissue mast cell numbers or by other unknown mechanisms. The findings suggest potential benefits of MOD000001 for allergic diseases involving IgE-mediated mast cell activation.

A rare case of food-dependent exercise-induced anaphylaxis caused by potato snacks is reported. Specific food triggers for anaphylaxis were identified by using the skin prick test, antigen analysis, and serum IgE assays. Four potato proteins were considered candidate antigens for food-dependent exercise-induced anaphylaxis.

ROS are involved in the pathogenesis of bullous pemphigoid (BP), but this involvement has not been fully elucidated. In this study, to further elucidate the pathogenic role of ROS in BP, we examined the results of the diacron-reactive oxygen metabolite test and the biological antioxidant potential test for 16 patients with BP who visited our hospital before being treated with systemic corticosteroids. In the patients with BP, the average diacron-reactive oxygen metabolite levels, expressed in Carratelli units, were significantly reduced at 1 month of treatment (from 335.6 ± 40.3 Carratelli units to 224.7 ± 61.6 Carratelli units, P < .001). Bullous Pemphigoid Disease Area Index (erosions/blisters) scores correlated with diacron-reactive oxygen metabolite levels (r = 0.51), suggesting that those levels reflect the disease severity. We also performed staining of 3,5-dibromotyrosine in skin tissues. The 3,5-dibromotyrosine is expected to be a marker of tissue damage related to inflammation and allergies. The 3,5-dibromotyrosine was stained in infiltrated cells around the dermis, throughout the blister fluid, and at the basement membrane within the blister. It is considered that tissue destruction caused by the myeloperoxidase released from neutrophils and by eosinophil peroxidase released from eosinophils is involved in blister formation. The results suggest that ROS play a role in BP.

Background: To date, few studies from the Asian region have reported the effectiveness of messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccines against disease progression and death after hospitalization. Methods: We evaluated the data from the COVID-19 registry in Japan during the delta- and omicron-dominant phases. A propensity score-matched cohort study was conducted between the incompletely (0–1 dose) and fully (2 doses) vaccinated groups during the delta-dominant phase and among the incompletely, fully, and booster (3 doses) vaccinated groups during the omicron-dominant phase. Results: In the delta-dominant phase, 411 pairs were matched. The fully vaccinated group showed a significantly lower oxygen supplementation rate (24.1 % vs. 41.1 %, p

Background/objectives: Butyrylcholinesterase (BChE), a liver-derived enzyme that hydrolyzes acylated ghrelin to des-acylated ghrelin, may trigger a potential mechanism responsible for the acute exercise-induced suppression of acylated ghrelin. However, studies examining the effects of an acute bout of high-intensity exercise on BChE and acylated ghrelin have yielded inconsistent findings. This study aimed to examine the acute effects of exercise intensity on BChE, acylated ghrelin and des-acylated ghrelin concentrations in humans. Methods: Fifteen young men (aged 22.7 ± 1.8 years, mean ± standard deviation) completed three, half-day laboratory-based trials (i.e., high-intensity exercise, low-intensity exercise and control), in a random order. In the exercise trials, the participants ran for 60 min (from 09:30 to 10:30) at a speed eliciting 70 % (high-intensity) or 40 % (low-intensity) of their maximum oxygen uptake and then rested for 90 min. In the control trial, participants sat on a chair for the entire trial (from 09:30 to 12:00). Venous blood samples were collected at 09:30, 10:00, 10:30, 11:00, 11:30 and 12:00. Results: The BChE concentration was not altered over time among the three trials. Total acylated and des-acylated ghrelin area under the curve during the first 60 min (i.e., from 0 min to 60 min) of the main trial were lower in the high-intensity exercise trial than in the control (acylated ghrelin, mean difference: 62.6 pg/mL, p

We aimed to introduce a novel semi-automatic design approach for fabricating individualized, three-dimensional printed template dedicated to interstitial brachytherapy in vaginal tumor treatment. The central component of this concept involved the development of a cylindrical template with strategically placed tunnels to optimize applicator placement. These tunnels originated from the template's base, meticulously designed to prevent any potential overlap or interference. For precise tumor localization, we employed a method wherein the tumor's mask image was projected onto a spherical surface. Subsequently, we employed the k-means algorithm to segment the terminal points, with each cluster's center serving as the terminal point. To ensure the optimal starting point for the tunnels, we utilized the conjugate gradient method, considering the following factors: inter-starting point distance, angles between tunnels, inter-tunnel distance, and the starting point's position relative to the base of the template (inside or outside). We established a semi-automatic design paradigm for fabricating three-dimensional printed template tailored for vaginal brachytherapy. While our initial findings are promising, further comprehensive investigations are imperative to validate the clinical efficacy of this innovative concept.

Escherichia albertii is an emerging foodborne pathogen that causes diarrhea. E. albertii has been isolated from various foods, including pork and chicken meat, and environmental waters, such as river water. Although many food poisoning cases have been reported, there have been insufficient analyses of bacterial population behaviors in food and environmental water. In this study, we inoculated 2–5 log CFU of E. albertii into 25 g of pork, chicken meat, Japanese rock oyster, Pacific oyster, and 300 mL of well water and seawater at 4°C, 10°C, 20°C, and 30°C, and analyzed the bacterial population behavior in food and environmental water. After 3 days at 4°C, the population of E. albertii strain EA21 and EA24 in foods maintained approximately 4 log CFU/25 g. After 3 days at 10°C, the population of E. albertii strains in pork and oysters maintained approximately 4 log CFU/25 g, and that in chicken meat increased to approximately 5–6 log CFU/25 g. After 2 days at 20°C, E. albertii strains grew to approximately 6–7 log CFU/25 g in pork and chicken meat, and E. albertii strain EA21 but not EA24 grew to 4.5 log CFU/25 g in Japanese rock oyster, E. albertii strain EA21 but not EA24 slightly grew to 3.1 log CFU/25 g in Pacific oyster. After 1 day at 30°C, E. albertii strains grew to approximately 7–8 log CFU/25 g in chicken meat and pork, grew to approximately 4–6 log CFU/25 g in Japanese rock oyster, and 6–7 log CFU/25 g in Pacific oyster. These results suggest that E. albertii survives without growth below 4°C and grew rapidly at 20°C and 30°C in foods, especially in meat. E. albertii strains did not grow in well water and seawater at 4°C, 10°C, 20°C, and 30°C. The population of E. albertii strains in well water and seawater decreased faster at 30°C than at 4°C, 10°C, and 20°C, suggesting that E. albertii has low viability at 30°C in environmental water.

Background: Immediate allergy caused by natto, a popular Japanese food prepared by fermenting soybeans with Bacillus subtilis var. natto, has been reported. Polygamma glutamic acid (PGA) in the sticky substance around natto beans has been reported to be a causative allergen of natto allergy. However, some of our patients with natto allergy were negative for PGA in the skin prick test (SPT). The sticky substance of natto beans contains a subtilisin family serine protease, nattokinase, along with PGA. In this study, we aimed to examine the antigenicity of nattokinase in natto allergy. Methods: Eight patients, who developed symptoms after ingesting natto and positively reacted to natto (seven to the sticky substance in natto and one to the whole natto product) in their SPT, were enrolled in this study. To analyze IgE reactivity, we performed immunoblotting, ELISA, and SPT for natto (bean and sticky substance), and/or PGA, and/or nattokinase and/or cultured B. subtilis var. natto extract. Results: In the SPT, four cases each were PGA-positive and PGA-negative. Immunoblotting of the sera from PGA-negative patients showed a protein band at 30 kDa, which was identified as nattokinase. Three PGA-negative cases, but not three PGA-positive cases, showed a positive reaction to nattokinase in the SPT and had a history of atopic dermatitis. The ELISA for nattokinase revealed a positive reaction of PGA-negative cases and negative reaction of PGA-positive cases in the SPT. Conclusions: We identified a subtilisin family serine protease, nattokinase, as a novel allergen in natto allergy patients unsensitized to PGA.

Background/purpose: Dental hygiene students' stress might be rising with increasing undergraduate study content and expansions in dental hygienists' roles and expectations as society changes. This study explored Japanese and Taiwanese dental hygiene students’ perceptions of stress and their idea of career planning. Materials and methods: Participants were second- to fourth-year students in the 2020 academic year at Tokyo Medical and Dental University (TMDU; n = 60) and Taipei Medical University (TMU; n = 62). An anonymous questionnaire was distributed, which included questions on demographic information and career planning, as well as the Perceived Stress Scale-10 (PSS-10) and modified Dental Environment Stress questionnaire (DES). Results: The response rates were 100.0% (TMDU) and 96.8% (TMU). The number of participants who chose dental hygiene as the first program choice (P

Background: In Japan, pollinosis caused by the Japanese cypress (JCy) Chamaecyparis obtusa is among the very common seasonal allergies. In JCy pollinosis, Cha o 1 is the first major allergen, and Cha o 2 is the second major allergen. Recently, Cha o 3 was identified as a new JCy pollen allergen in JCy pollinosis. However, the relative contribution of Cha o 3 to JCy pollinosis compared with that of Cha o 1 and that of Cha o 2 has not been fully elucidated. Objective: This study aimed to clarify the allergenicity of Cha o 3 compared with that of Cha o 1 and Cha o 2 in JCy pollinosis. Methods: We recruited 27 patients with JCy pollinosis and performed the basophil activation test (BAT) with native (n) Cha o 1, Cha o 2, and Cha o 3 purified from JCy pollen. In addition, we a performed JCy-specific IgE suppression test. Results: In the BAT, 26 of 27 patients (96%) and 18 of 27 patients (67%) showed positive basophil activation in response to n Cha o 1 and n Cha o 2, respectively, as judged by CD203c expression. Little CD203c expression in response to n Cha o 3 was seen. The presence of n Cha o 3 marginally reduced the titer levels of JCy-specific IgE. Conclusion: Cha o 3 showed little ability to activate basophils and suppress JCy-specific IgE titers compared with Cha o 1 or Cha o 2 in patients with JCy pollinosis. Thus, Cha o 3 may not be a major allergen in JCy pollinosis.

ABSTRACT: Objectives: Linezolid is an antibiotic used to treat infectious diseases caused by vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Recently, Enterococcus Spp.–carrying mobile linezolid resistance genes were reported. Herein, we report the complete genome sequence of Enterococcus raffinosus JARB-HU0741, which was isolated from a bile sample of a patient in Japan on May 5, 2021, and carries a linezolid resistance gene, cfr(B). Nevertheless, this isolate was susceptible to linezolid. Methods: Whole-genome sequencing was performed using HiSeq X FIVE (Illumina) and GridION (Oxford Nanopore Technologies). The sequence reads were assembled using Unicycler v0.4.8, and the complete genome was annotated using DFAST v1.2.18. Antimicrobial resistance genes were detected with Abricate v1.0.1, using the ResFinder database. The minimum inhibitory concentrations (MICs) were determined using broth microdilution and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. Results: E. raffinosus JARB-HU0741 contained a 3 248 808-bp chromosome and a 1 156 277-bp megaplasmid. cfr(B) was present in the Tn6218-like transposon, which was inserted into a gene encoding a PRD domain–containing protein present in the megaplasmid, but the isolate was susceptible to linezolid (MIC, 0.5 µg/mL). The Tn6218-like transposon was similar to the Tn6218 of Clostridioides difficile Ox3196 and the Tn6218-like transposon of Enterococcus faecium UW11733; however, three genes encoding a topoisomerase, an S-adenosylmethionine-dependent methyltransferase, and a TetR family transcriptional regulator were present in the previous Tn6218- or Tn6218-like transposon. Conclusion: This is the first report of the complete genome sequence of E. raffinosus carrying cfr(B). E. raffinosus carrying cfr(B) without linezolid resistance poses a threat, as it could serve as a reservoir for mobile linezolid resistance genes.

Objective: Preserving core body temperature across a wide range of ambient temperatures requires adaptive changes of thermogenesis that must be offset by corresponding changes of energy intake if body fat stores are also to be preserved. Among neurons implicated in the integration of thermoregulation with energy homeostasis are those that express both neuropeptide Y (NPY) and agouti-related protein (AgRP) (referred to herein as AgRP neurons). Specifically, cold-induced activation of AgRP neurons was recently shown to be required for cold exposure to increase food intake in mice. Here, we investigated how consuming a high-fat diet (HFD) impacts various adaptive responses to cold exposure as well as the responsiveness of AgRP neurons to cold. Methods: To test this, we used immunohistochemistry, in vivo fiber photometry and indirect calorimetry for continuous measures of core temperature, energy expenditure, and energy intake in both chow- and HFD-fed mice housed at different ambient temperatures. Results: We show that while both core temperature and the thermogenic response to cold are maintained normally in HFD-fed mice, the increase of energy intake needed to preserve body fat stores is blunted, resulting in weight loss. Using both immunohistochemistry and in vivo fiber photometry, we show that although cold-induced AgRP neuron activation is detected regardless of diet, the number of cold-responsive neurons appears to be blunted in HFD-fed mice. Conclusions: We conclude that HFD-feeding disrupts the integration of systems governing thermoregulation and energy homeostasis that protect body fat mass during cold exposure.

Summary: Background: The increasing incidence of multidrug-resistant Gram-negative bacteria causing ventilator-associated pneumonia (VAP) is a global concern. A better understanding of the epidemiology of VAP in Southeast Asia is essential to optimise treatments and patient outcomes. Methods: VAP epidemiology in an intensive care unit in Vietnam was investigated. A prospective cohort study was conducted. Patients who were ventilated for >48 hours, diagnosed with VAP, and had a positive respiratory culture between October 2015 and March 2017 were included. Whole-genome sequencing (WGS) was performed on Acinetobacter baumannii isolates. Results: We identified 125 patients (137 episodes) with VAP from 1,699 admissions. Twelve patients had 2 VAP episodes. The median age was 60 years (interquartile range: 48–70), and 68.8% of patients were male. Diabetes mellitus was the most frequent comorbidity (N=35, 28%). Acinetobacter baumannii was most frequently isolated in the first VAP episode (N=84, 67.2%) and was multiply resistant to meropenem, levofloxacin, and amikacin. The 30-day mortality rate was 55.2% (N=69) and higher in patients infected with A. baumannii (N=52, 65%). WGS results suggested a complex spread of multiple clones. Conclusions: In an intensive care unit in Vietnam, VAP due to A. baumannii had a high mortality rate, and A. baumannii and K. pneumoniae were multidrug resistant, with carbapenem resistance of 97% and 70%, respectively.

Gestational trophoblastic disease (GTD) is an abnormal pregnancy caused by the placenta, which can potentially metastasise. Suction evacuation is recommended for diagnosis and treatment, and dilatation and evacuation (D&E) is usually performed under intravenous anaesthesia due to the short operation time and minimal blood loss. We refer to the guidelines produced by the Japan Society of Obstetrics and Gynaecology (JSOG), and acknowledge that practices vary globally. However, to the best of our knowledge, there is no evidence on perioperative management and arrangements in D&E required for managing giant hydatidiform moles, such as preventing massive haemorrhage, respiratory dysfunction with a pathogenesis like ovarian hyperstimulation syndrome (OHSS), or intensive care needs. This case report describes perioperative considerations for managing a giant hydatidiform mole using D&E in a uterus enlarged to the third-trimester pregnancy size. A 28-year-old multiparous woman was clinically diagnosed with a hydatidiform mole after a spontaneous miscarriage due to abnormal genital bleeding, systemic oedema, and abdominal distention. Ultrasound and computed tomography showed a ballooning uterus with a third-trimester pregnancy size, a robust intrauterine mass, and ascites. Serum hCG levels were extremely high (>3,000,000 mIU/mL), confirming the clinical diagnosis of a hydatidiform mole. Emergency D&E was safely performed under multidisciplinary perioperative management, with careful preparation and support. This is a rare experience-based case report and valuable documentation detailing multidisciplinary perioperative management under general anaesthesia. To the best of our knowledge, this is the first report describing the considerations, details, and innovations required in the perioperative management of giant hydatidiform moles using D&E.

Background: The impact of coronary bifurcation angle (BA) on incomplete stent apposition (ISA) after crossover stenting followed by side branch (SB) intervention has not been established. Methods: A total of 100 crossover stentings randomly treated with proximal optimization technique followed by short balloon dilation in the SB (POT-SBD group, 48 patients) and final kissing balloon technique (KBT group, 52 patients) were analyzed in the PROPOT trial. Major ISA with maximum distance > 400 μm and its location was determined using optical coherence tomography before SB intervention and at the final procedure. The BA was defined as the angle between the distal main vessel and SB. Optimal POT was determined when the difference in stent volume index between the proximal and distal bifurcation was greater than the median value (0.86 mm3/mm) before SB intervention. Result: Major ISA was more frequently observed in the POT-SBD than in the KBT group (35% versus 17%, p

ABSTRACT: Objectives: The occurrence of linezolid resistance in enterococci has recently increased. Here, we report the genomic characterization of Enterococcus faecalis strain JARB-HU0796—isolated from the open pus of a patient in Hiroshima, Japan—which shows nonsusceptibility to linezolid (MIC of 4 µg/mL). Methods: JARB-HU0796 whole-genome sequencing was performed using short-read sequencing with Illumina Hiseq X Five and long-read sequencing using GridION. These reads were collected using the assembly pipeline Unicycler and annotated with DFAST. Antimicrobial resistance genes were detected using the Abricate and ResFinder databases, and the sequence type identified using PubMLST. The antimicrobial susceptibility of JARB-HU0796 was determined with the Eiken dry-plate QH02 system. Results: The JARB-HU0796 complete genome contained a circular chromosome (2 722 585 bp) and two circular plasmids (85 996 bp and 58 872 bp). The chromosome harbours the optrA gene, which confers resistance to oxazolidinones and phenicols. JARB-HU0796 showed nonsusceptibility to linezolid and multidrug resistance to other antibiotics. MLST analysis identified JARB-HU0796 as ST476, similar to the optrA-positive E. faecalis ST476 isolates from swine (South Korea, 2020) and pet food (Switzerland, 2022). The optrA region of JARB-HU0796 is nearly identical to that of ST476 E. faecalis strain TZ2, isolated from humans (China, 2013). Conclusions: To the best of our knowledge, this is the first report of the complete genome sequence of E. faecalis ST476 carrying optrA on a chromosome isolated from a patient in Japan. The strain may have originated in animals, suggesting that the organisms acquired resistance to linezolid because the optrA gene may be closely spread between animals and humans.

Background/purpose: Although dental diseases are related to systemic diseases and daily habits and are known to affect the quality of life, little attention has been paid to the importance of oral hygiene in Japanese working-age adults. We, thus, aimed to assess changes in the periodontal condition of working-age adults after providing regular oral health information at their workplace for two years. Materials and methods: Two years of oral health information were provided to workers at four printing companies. The effectiveness thereof was assessed using gingival crevicular fluid (GCF) test results—lactoferrin (Lf), alpha-1-antitrypsin (AT), and aspartate aminotransferase (AST). Questionnaires on health literacy (HL) and dental terminology were also administered to the workers during annual check-ups. Results: The baseline survey participants included were 234 male workers, of which 104 workers followed the same work schedule/day–night shifts and completed the two-year follow-up survey were examined. Providing continuous oral health information with regular updates did not improve participants’ self-administered GCF tests (Lf: P = 0.272, AT: P = 0.723, and AST: P = 0.067), and there were no significant changes in HL, perceived symptoms, and use of interdental cleaning tools. Conclusion: Direct oral health education or examination might be necessary for working-age adults to achieve optimum oral conditions, and one-on-one health information provision might not improve their oral condition. A combination of methods to provide oral health promotion must be considered.

Background/purpose: Human periodontal ligament consists of elastic system fibers, mainly fibrillin-1 (FBN1). Periostin (POSTN) maintains periodontal homeostasis. A previous study showed that the expression of Postn in periodontal ligament cells was decreased in mice underexpressing Fbn1. However, the relationship between FBN1 and POSTN is not fully understood in the context of mechanical stress. FBN1 contributes to transforming growth factor β1 (TGF-β1) activation; TGF-β1 upregulates the expression of POSTN in human periodontal ligament cells. This study examined whether FBN1 contributed to the maintenance of periodontal homeostasis in cultured human periodontal ligament cells. Materials and methods: Human periodontal ligament fibroblasts (HPDLFs) were exposed to mechanical force via centrifugation. The expression of POSTN was examined by quantitative reverse transcription polymerase chain reaction. The phosphorylation of Smad2 in the TGF-β/Smad signaling pathway was monitored by western blotting. Results: The expression levels of FBN1 and POSTN were not significantly decreased by centrifugation. However, the expression of POSTN after centrifugation significantly decreased upon knockdown of FBN1. The phosphorylation of Smad2 after centrifugation was decreased, regardless of FBN1 knockdown. Supplementation with 0.1 ng/ml recombinant human TGF-β1 rescued POSTN expression after centrifugation in HPDLFs upon knockdown of FBN1. Conclusion: FBN1 regulates the expression of POSTN to maintain periodontal homeostasis via TGF-β/Smad signaling during centrifugation.

Background: Some patients with wheat allergy have been reported to show clinical cross-reactivity to barley. However, it is not clear whether the development of barley allergy in patients with wheat allergy is due to cross-antigenicity between wheat and barley. This study aimed to determine the clinical cross-reactivity and immunological cross-antigenicity of wheat and barley. Methods: The results of barley oral food challenges (OFCs) were compared before and after oral immunotherapy (OIT) for wheat in nine patients with wheat allergy to estimate the clinical cross-reactivity of wheat and barley. Moreover, we performed enzyme-linked immunosorbent assay (ELISA) inhibition and immunoblotting inhibition using serum from seven patients allergic to wheat and barley. Results: Nine patients who had positive barley-OFC results performed before OIT for wheat were all negative on barley-OFC performed after OIT. In ELISA inhibition, preincubation of serum from patients allergic to wheat and barley with a high barley extract concentration inhibited binding of IgE to wheat extract by less than 10%. On the other hand, wheat and barley extracts equally inhibited binding to barley sIgE at high concentrations. In the immunoblotting inhibition test, the spots of wheat were inhibited but weakly by barley extracts, and most of the spots of barley were inhibited even by low concentrations of the wheat and barley extract. Conclusions: We showed that barley allergy associated with wheat allergy is caused by cross-reactivity from wheat. The OIT for wheat is one of the promising options for barley allergy.

Background: The role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody response from natural infection and vaccination, and the potential determinants of this response are poorly understood. Characterizing this antibody response and the factors associated with neutralization can help inform future prevention efforts and improve clinical outcomes in those infected. Objectives: The goals of this study were to prospectively evaluate SARS-CoV-2 antibody levels and the neutralizing antibody responses among naturally infected adults and to determine demographic and behavioral factors independently associated with these responses. Methods: Serum was collected from seropositive individuals at baseline, four-weeks, and three-months following their first study visit to be evaluated for antibody levels. Detection of neutralizing antibodies was performed at baseline. Participant demographic and behavioral information was collected via web questionnaire prior to their first visit. Results: At baseline, higher antibody levels were associated with better neutralization capacity, with 83% of participants having detectable neutralizing antibodies. We found an age-dependent effect on antibody level and neutralization capacity with participants over 65 years having significantly higher levels. Ethnicity, heart disease, autoimmune disease, and COVID symptoms were associated with higher antibody levels, but not with increased neutralization capacity. Work environment during the pandemic correlated with increased neutralization capacity, while kidney or liver disease and traveling out of state after February 2020 correlated with decreased neutralization capacity, however neither correlated with antibody levels. Conclusions: Our data show that natural infection by SARS-CoV-2 can induce a humoral response reflected by high antibody levels and neutralization capacity.

In this study, we evaluate the effects of Weizmannia coagulans SANK70258 intake on skin condition and defecation, both alone and in combination with galacto-oligosaccharides, by conducting a randomized, double-blind, parallel-group, placebo-controlled, eight-week study of 45 healthy individuals. The primary endpoints were measurement of the stratum corneum moisture content, transepidermal water loss, and skin texture; the secondary endpoints were skin assessment, a defecation survey, and measurement of fecal organic acid and p-cresol contents. The participants were divided into a W. coagulans SANK70258 alone (lac + dex) group, a W. coagulans SANK70258 plus galacto-oligosaccharides (lac + gal) group, and a placebo (dex) group. The lac + gal group showed a decrease in skin roughness and fecal p-cresol content. Scaliness was improved in lac + dex and lac + gal groups. Thus, synbiotics combining W. coagulans SANK70258 and galacto-oligosaccharides can improve scaliness and skin roughness and reduce fecal p-cresol content.

We previously showed that social stress exposure in mature adult mice increased blood corticosterone concentrations at 2 days, disrupted hepatic lipid metabolism-related pathway at 30 days, and increased the risk of overweight with hepatic hypertrophy at 90 days. To further investigate the effects of aging on the physiological responses to social stress, we conducted a study using male BALB/c mice at the ages of 2 months (mature age), 14 months (middle age) and 26 months (old age), and exposed them to confrontation stress for 2 or 7 days. Blood corticosterone concentrations were increased at 2 days of stress, and then returned to baseline concentrations. This change was observed only at 2 months of age. We further examined the effect of aging on hepatic gene expression of fibroblast growth factor-21 (Fgf21) and found that its expression was significantly decreased after 7 days of stress at 14 months of age and after 2 days of stress at 26 months of age, indicating these decreasing effects became more pronounced with age. In conclusion, our study suggests that hepatic Fgf21 expression decrease under exposure to confrontation stress at middle or more age, indicating that stress response on Fgf21 related pathway might be more pronounced with age when exposed to stress.

Objectives: To evaluate the effectiveness of remdesivir in the early stage of nonsevere COVID-19. Although several randomized controlled trials have compared the effectiveness of remdesivir with that of a placebo, there is limited evidence regarding its effect in the early stage of nonsevere COVID-19 cases. Methods: We evaluated the effectiveness of remdesivir in the early stage of nonsevere COVID-19 using the COVID-19 Registry Japan, a nationwide registry of hospitalized patients with COVID-19 in Japan. Two regimens (“start remdesivir” therapy within 4 days from admission versus no remdesivir during hospitalization) among patients without the need for supplementary oxygen therapy were compared by a 3-step processing (cloning, censoring, and weighting) method. The primary outcome was a supplementary oxygen requirement during hospitalization. Secondary outcomes were 30-day in-hospital mortality and the risk of invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO). The data of 12,487 cases met our inclusion criteria. The “start remdesivir” regimen showed a lower risk of supplementary oxygen requirement (hazard ratio [HR]: 0.850, 95% confidence interval [CI]: 0.798–0.906, p value < 0.001). Both 30-day in-hospital mortality and risk of IMV/ECMO introduction were not significantly different between the 2 regimens (HRs: 1.04 and 0.983, 95% CI: 0.980–1.09 and 0.906–1.07, p values: 0.210 and 0.678, respectively). Conclusions: Remdesivir might reduce the risk of oxygen requirement during hospitalization in the early stage of COVID-19; however, it had no positive effect on the clinical outcome and reduction in IMV/ECMO requirement.

Background/purpose: As the number of patients with osteoporosis requiring orthodontic treatment is increasing with the aging of society, it is necessary to evaluate the relations between bone metabolism in old age and orthodontic tooth movement (OTM). However, the effects of changes in bone metabolism due to osteoporosis on OTM and root resorption are still unclear. Therefore, we investigated the effects of OTM and root resorption in a mouse ovariectomy (OVX)-induced osteoporosis model. Materials and methods: Eight-week-old female wild-type mice underwent OVX or sham surgery (Sham) as controls. One month after treatment, a nickel titanium coil spring was used to apply a mesial force to the maxillary left first molars of OVX or Sham mice for 12 days. The distance between the maxillary first molar and the second molar changed due to OTM and osteoclast formation was evaluated. The odontoclast formation and root resorption along the root surface of the distobuccal root of the first molar was also evaluated by histological analysis and scanning electron microscopy. Results: Distance of tooth movement and osteoclast formation were significantly increased in OVX mice compared to Sham controls. Furthermore, root resorption in the mesial surface of the distal molars induced by orthodontic force was significantly increased in OVX mice. Conclusion: The amount of OTM was significantly increased, and the accompanying root resorption was also increased in OVX mice. Therefore, attention should be paid to the risk of root resorption associated with orthodontic treatment in patients with osteoporosis.

Summary: Background: While a number of observational studies of enteral nutrition (EN) during mechanical circulatory support (MCS) have been conducted, fewer have looked into severe acute heart failure (AHF), specifically. Methods: This retrospective observational study investigated patients admitted to a single cardiac care unit from January 2014 to March 2020 for AHF and requiring invasive mechanical ventilation within 72 hours of admission. We investigated clinical outcomes and EN complications in the group of patients for whom EN was initiated during MCS (MCS group). The primary outcome was 30-day mortality. Results: Forty-seven patients in the MCS group met the inclusion criteria. The 30-day mortality rate was 32% (15) in the MCS group. The number of patients with EN complications were 24 [51%] in the MCS group. Multivariate analysis revealed that no association found between EN initiation during MCS and the 30-day mortality rate and EN complications. (OR:0.94, 95% CI:0.27–3.23, P = 0.922, OR:1.29, 95% CI:0.31–5.29, P = 0.724, respectively). Conclusion: EN can be selected as the feeding route during MCS, because the adverse events and intolerance associated with EN initiation is not increased when the patients with severe AHF were made hemodynamically stable using MCS.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most prevalent mycobacteria causing non-tuberculous mycobacterial disease in humans and animals. Of note, MAH is a major cause of mycobacterial granulomatous mesenteric lymphadenitis outbreaks in pig populations. To determine the precise source of infection of MAH in a pig farm and to clarify the epidemiological relationship among pig, human and environmental MAH lineages, we collected 50 MAH isolates from pigs reared in Japan and determined draft genome sequences of 30 isolates. A variable number of tandem repeat analysis revealed that most pig MAH isolates in Japan were closely related to North American, European and Russian human isolates but not to those from East Asian human and their residential environments. Historical recombination analysis revealed that most pig isolates could be classified into SC2/4 and SC3, which contain MAH isolated from pig, European human and environmental isolates. Half of the isolates in SC2/4 had many recombination events with MAH lineages isolated from humans in East Asia. To our surprise, four isolates belonged to a new lineage (SC5) in the global MAH population. Members of SC5 had few footprints of inter-lineage recombination in the genome, and carried 80 unique genes, most of which were located on lineage specific-genomic islands. Using unique genetic features, we were able to trace the putative transmission route via their host pigs. Together, we clarify the possibility of species-specificity of MAH in addition to local adaptation. Our results highlight two transmission routes of MAH, one exposure on pig farms from the environment and the other via pig movement. Moreover, our study also warns that the evolution of MAH in pigs is influenced by MAH from patients and their residential environments, even if the MAH are genetically distinct.

Objectives: Daily step counts are an easy-to-understand indicator of physical activity; however, there is limited evidence regarding the optimal daily step count to prevent sarcopenia. This study examined the dose-response relationship between daily step count and the prevalence of sarcopenia and explored the optimal dose. Design: Cross-sectional study. Setting and participants: The study included 7949 community-dwelling middle-aged and older adults (aged 45–74 years) from Japan. Measurements: Skeletal muscle mass (SMM) was assessed using bioelectrical impedance spectroscopy, and muscle strength was quantified through handgrip strength (HGS) measurement. Participants who exhibited both low HGS (men:

Background: The ecological vulnerability assessment (EVA) is employed as a tool for integrated evaluation of the ecosystem with the help of indicators belonging to natural, social, and economy systems. The unavailability of suitable datasets has repeatedly been reported as an obstacle to conducting EVA on large spatial and temporal scales. The progress in remote sensing (RS) technology has aided the development of ecological vulnerability indicators (EVIs) from RS datasets. Scope and approach: This manuscript presents a comprehensive review of 80 peer-reviewed publications which uses RS for EVA. In this regard, the paper is divided into five main sections: First, the background and rationale of conducting this review is presented in the introduction. Second, the methodology for selection and interpretation of selected literature is discussed. Then, the results section presents findings from various dimensions: general trend of literature, spatial or temporal scale of EVA, analysis of targets systems, RS and Non-RS derived EVIs, sensors used for acquisition of RS data, conceptual models, weights determining mechanisms, and software. Next, multiple gaps in the body of knowledge are identified and general recommendations are formulated for future researchers. Finally, the link of EVA with sustainable development is highlighted in the conclusion section. Key findings: The overall trend shows that both the quantity and quality of research regarding EVA has increased over the past decades. It is observed that large number of studies report EVA on both temporal and spatial scale. Further, the results reveal 52 EVIs are derived from RS data and 101 EVIs are derived from non-RS data. The Landsat datasets are found most repeatedly used in EVA research. The remote sensing ecological index (RSEI) and principal component analysis (PCA) are prominent conceptual models and weighting mechanisms. Finally, ArcGIS software is most widely reported software in the EVA literature.

Background/purpose: Tooth movement that is achieved using orthodontic mechanical principles relies on bone resorption which takes place on the compression side via osteoclasts. Tumor necrosis factor-α (TNF-α) has been known to affect osteoclast formation in orthodontic tooth movement (OTM). Vascular endothelial growth factor (VEGF), which is one of the mediators of angiogenesis, also plays an important role in OTM by inducing vascular permeability and chemotaxis of osteoclast precursors. Therefore, the purpose of this research was to evaluate the effect of TNF-α on VEGF expression during OTM. Materials and methods: In order to demonstrate the effect of TNF-α on VEGF expression during OTM, a nickel titanium closed coil spring was fixed to the upper left first molar and the alveolar bone beneath the upper incisors of both wild type (WT) and TNF receptors (TNFRs) deficient mice resulting in a mesial movement of the molar for 12 days. The maxilla was removed for histological analysis and real-time RCR analysis of VEGF expression. Results: Immunohistochemical analysis revealed that there were fewer VEGF-positive cells in the periodontal membrane on the mesial side of the distobuccal root in TNFRs-deficient mice than that in WT mice during the OTM for 12 days. Furthermore, expression of VEGF mRNA is lower level in TNFRs-deficient mice than that in WT mice. Conclusion: Our results indicate that TNF-α plays an important role in VEGF expression during tooth movement.

Background: Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum are commensal bacteria that are associated with colonization and infection of the urogenital tract. However, colonization of the respiratory tract by these microorganisms in adults has not been fully investigated. Methods: Urine and respiratory tract samples (sputum, tracheal aspirates, and bronchoalveolar lavage) of patients aged 20−80 years were analyzed to detect the presence of M. hominis, U. parvum, and U. urealyticum using a conventional PCR method. The samples were submitted to the microbiological clinical laboratory of Hiroshima University Hospital from December 1, 2021 to May 31, 2022. Results: In total, 334 urine and 238 respiratory tract samples were analyzed. The overall detection rates of M. hominis, U. parvum, and U. urealyticum were 2.9%, 1.7%, and 2.3% in male urine; 7.0%, 13.8%, and 1.9% in female urine; 2.2%, 0%, and 2.2% in male respiratory tract; and 0%, 2.0%, and 0% in female respiratory tract, respectively. In urine samples, the detection rates of M. hominis, U. parvum, and U. urealyticum were significantly higher (p

Summary: Various parasitic flatworms infect vertebrates for sexual reproduction, often causing devastating diseases in their hosts. Consequently, flatworms are of great socioeconomic and biomedical importance. Although the cessation of parasitic flatworm sexual reproduction is a major target of anti-parasitic drug design, little is known regarding bioactive compounds controlling flatworm sexual maturation. Using the planarian Dugesia ryukyuensis, we observed that sex-inducing substances found in planarians are also widespread in parasitic flatworms, such as monogeneans and flukes (but not in tapeworms). Reverse-phase HPLC analysis revealed the sex-inducing substance(s) eluting around the tryptophan retention time in the fluke Calicophoron calicophorum, consistent with previous studies on the planarian Bipalium nobile, suggesting that the substance(s) is likely conserved among flatworms. Moreover, six of the 18 ovary-inducing substances identified via transcriptome and metabolome analyses are involved in purine metabolism. Our findings provide a basis for understanding and modifying the life cycles of various parasitic flatworms.

ABSTRACT: Objectives: To determine whether anticoagulation therapy improves outcomes in patients with coronavirus disease 2019 (COVID-19) in Japan given their lower risk of thrombosis compared with Western cohorts. Methods: The efficacy of anticoagulation therapy in hospitalized patients with COVID-19 was evaluated using a nationwide registry: the COVID-19 Registry Japan. The inverse probability of weight treatment method was used to adjust for baseline confounders in the anticoagulation and non-anticoagulation groups. Results: Of the 1748 patients included, anticoagulants were used in 367 patients (treatment group). The patients in the anticoagulant group were older, predominantly male, and often presented with obesity, hyperlipidaemia, hypertension, diabetes and elevated D-dimer levels. Twenty-nine-day mortality was 7.6% in the whole cohort (treatment group, 11.2%; no treatment group, 6.6%), 6% in patients who were not treated with steroids (treatment group, 12.3%; no treatment group, 5.2%), and 11.2% in patients treated with steroids (treatment group, 10.5%; no treatment group, 11.8%). Mortality in the whole cohort was similar between the treatment and no treatment groups (P=0.99), and an insignificant decreasing trend in mortality was observed in patients treated with steroids (P=0.075). Conclusions: Anticoagulants may be beneficial in Asians, in whom comorbidities and risk of thrombosis may differ from other ethnic groups.

Background/purpose: Orthodontic tooth movement (OTM) is facilitated by two events; bone resorption on the compression side and bone formation on the tension side simultaneously termed bone remodeling. Osteocytes play a critical role in bone remodeling during OTM, as they have been described as the critical source of nuclear factor-κB ligand (RANKL) necessary for bone remodeling during OTM. Tumor necrosis factor (TNF)-α is a cytokine that acts by amplifying RANKL expression in osteocytes. In this study, we evaluated the effects of TNF-α on RANKL expression in osteocyte during OTM. Materials and methods: We assessed whether TNF-α influenced RANKL expression in osteocyte during orthodontic tooth movement by using wild-type (WT) and TNF receptor I and II deficient (TNFRsKO) mice. A Nickel-titanium closed coil spring was attached to the maxillary alveolar bone near the incisors and the upper left first molar, and the first molars were moved mesially in WT and TNFRsKO mice. After OTM, the number of RANKL-positive osteocytes in the alveolar bone was evaluated by immunohistochemistry. Results: The number of RANKL-positive osteocyte in the alveolar bone significantly increased in WT mice than in TNFRsKO mice after OTM. Conclusion: The results indicate that TNF-α induces the expression of RANKL in osteocyte during OTM.