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Purpose: This study was performed to investigate the association of dental dysplasia with childhood cancer. We examined the occurrence of agenesis, microdontia, and enamel changes of permanent teeth in pediatric cancer survivors., Methods: Seventy-six patients with pediatric cancer and hematologic diseases were referred to our department for the first time from October 2005 to December 2019. Of these, 17 patients who presented for a checkup in our department fulfilled the study criteria and were analyzed. Clinical examinations and panoramic radiographs were performed to investigate dental dysplasia of permanent teeth. A total of 34 developmental abnormalities (18 missing teeth, 16 cases of microdontia) occurred in 5 patients. The patients' medical records were also analyzed to assess the relationships of specific types of dysplasia with the treatment duration and cumulative drug dose administered., Results: All five pediatric cancer survivors had dental dysplasia; all five had tooth agenesis, and four had microdontia. All five patients were < 4 years of age and had undergone high-dose chemotherapy., Conclusion: In this study, childhood cancer survivors who received high-dose chemotherapy before age 4 years experienced the dental dysplasia, including tooth agenesis, microdontia. These findings highlight the need for careful dental monitoring and early intervention in pediatric patients undergoing high-dose chemotherapy., Clinical Trial Number: This research was conducted in accordance with the Declaration of Helsinki and approved by the Medical Ethics Committee of the Medical University of Kobe (protocol code No. B230066, 1 September 2023)., Competing Interests: Declarations Ethics approval Approval was granted by the Medical Ethics Committee of the Medical University of Kobe, Hyogo, Japan, on 1 September 2023 (Approval No. B230066). Consent to participate The authors affirm that all patients or their guardians provided informed consent for publication of this report. Consent to publication Not applicable (the manuscript does not contain any form of personal data, including personal details, images, or videos). Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Primary tracheal diffuse large B-cell lymphoma (DLBCL) is a rare, aggressive, but potentially curable malignancy that is difficult to diagnose and treat. We herein report a 93-year-old Japanese man diagnosed with primary tracheal DLBCL after presenting with progressive dyspnea due to severe upper tracheal stenosis during follow-up for pulmonary amyloidosis. Following the diagnosis, the patient was treated with corticosteroids, followed by R-CHOP chemotherapy, resulting in a therapeutic response. The patient's history of pulmonary amyloidosis may have contributed to the development of tracheal DLBCL. An evaluation of the risks and benefits of various therapeutic interventions is crucial for providing optimal patient-specific care.

Introduction: Cardiac remodeling is defined as cellular interstitial changes that lead dysfunction of the heart after injury. Placental growth factor (PlGF), a member of the VEGF family, has been reported to regulate cardiac hypertrophy in hemodynamic state. We therefore analyze the function of PlGF during cardiac remodeling using cardiac cells and fibroblasts, under Angiotensin II (AngII) stimulation., Methods: PlGF overexpressed mouse embryonic fibroblasts derived from C57BL/6 mice, were made by deficient retrovirus vector, designated as C57/PlGF. Only retrovirus vector introduced C57 cells (C57/EV) were used as control. After AngII stimulation, wound scratching assay and MTT proliferation assay with or without p38 MAPK inhibitor, SB205580 were performed in retrovirally-introduced C57 cells. Reactive oxygen species (ROS) production, NF-kB activation, IL-6 and TNF-α production were also measured. Then we assessed AngII-induced cell proliferation of mouse cardiac fibroblasts (CFs) and rat primary cardiomyocytes incubating with C57/PlGF conditioned-medium., Results: The PlGF production in C57/PlGF were confirmed by ELISA (1093.48 ± 3.5 pg/ml, ±SE). AngII-induced cell migration, proliferation and H 2 O 2 production were increased in C57/PlGF compared with C57/EV. SB205580 inhibited the AngII-induced cell proliferation in C57/PlGF. In C57/PlGF cells, NF-kB activation was higher, followed by up-regulation of IL-6 and TNF-α production. CFs and cardiomyocytes proliferation increased when stimulated with C57/PlGF conditioned-medium., Discussion: The activation of fibroblast is stimulated by PlGF signaling via p38 MAPK/NF-kB pathway accompanied by elevation of ROS and inflammatory response. Furthermore, these signals stimulate the activation of CFs and cardiomyocytes, indicating that high circulating level of PlGF have a potential to regulate cardiac remodeling., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lisa Kitasato reports financial support was provided by Japan Society for the Promotion of Science. Minako Yamaoka-Tojo reports financial support was provided by Japan Society for the Promotion of Science. Lisa Kitasato reports financial support was provided by Bayer Academic Support. Lisa Kitasato reports financial support was provided by SRL research grant. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Optimal timing for intubating patients with coronavirus disease 2019 (COVID-19) has been debated throughout the pandemic. Early use of high-flow nasal cannula (HFNC) can help reduce the need for intubation, but delay can result in poorer outcomes. This study examines trends in laboratory parameters and serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA levels of patients with COVID-19 in relation to HFNC failure. Patients requiring HFNC within three days of hospitalization between July 1 and September 30, 2021 were enrolled. The primary outcome was HFNC failure (early failure ≤Day 3; late failure ≥Day 4), defined as transfer to intensive care just before/after intubation or in-hospital death. We examined changes in laboratory markers and SARS-CoV2-RNAemia on Days 1, 4, and 7, together with demographic data, oxygenation status, and therapeutic agents. We conducted a univariate logistic regression with the explanatory variables defined as 10% change rate in each laboratory marker from Day 1 to 4. We utilized the log-rank test to assess the differences in HFNC failure rates, stratified based on the presence of SARS-CoV2 RNAemia. Among 122 patients, 17 (13.9%) experienced HFNC failure (early: n = 6, late: n = 11). Seventy-five patients (61.5%) showed an initial SpO2/FiO2 ratio ≤243, equivalent to PaO2/FiO2 ratio ≤200, and the initial SpO2/FiO2 ratio was significantly lower in the failure group (184 vs. 218, p = 0.018). Among the laboratory markers, a 10% increase from Day 1 to 4 of lactate dehydrogenase (LDH) and interleukin (IL)-6 was associated with late failure (Odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.09-1.89 and OR: 1.04, 95%CI: 1.00-1.19, respectively). Furthermore, in patients with persistent RNAemia on Day 4 or 7, the risk of late HFNC failure was significantly higher (Log-rank test, p<0.01). In conclusion, upward trends in LDH and IL-6 levels and the persistent RNAemia even after treatment were associated with HFNC failure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Koyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lactobacillus spp. inhibit the growth of Campylobacter spp. in vitro . However, in chicken crops, in which Lactobacillus spp. predominate, such inhibition of Campylobacter has not been confirmed. In our previous study, feeding paddy rice to broiler chicks increased the residence time of the food, which might enhance the bactericidal activity of the crop. Here, the bactericidal activity against the remaining Campylobacter spp. in broiler crops was evaluated. A suspension prepared by mixing Campylobacter jejuni and titanium dioxide (TiO 2 ) was inoculated into the pharynx of 26-day-old broiler chicks fed a paddy rice-based diet. The crop contents were sampled at 20-min intervals. The TiO 2 residual ratio in the crop gradually decreased with time after inoculation, with 57% of the inoculated TiO 2 remaining in the crop 60 min after inoculation. The survival fraction of C. jejuni in the crops was 11% at 40 min, only 1% at 60 min, and was undetectable at 80 min. Most of the inoculated C. jejuni died in the crop before entering the next segment. These data indicated that bacterial death occurred between 30 min and 40 min after inoculation. The average survival time of C. jejuni in the crop was calculated to be 37.1 min. Thus, C. jejuni remaining in a chicken crop for more than 40 min died., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest., (2024 Japan Poultry Science Association.)

The increasing requirement of mechanical ventilation (MV) due to the novel coronavirus disease (COVID-19) is still a global threat. The aim of this study is to identify markers that can easily stratify the impending use of MV in the emergency room (ER). A total of 106 patients with COVID-19 requiring oxygen support were enrolled. Fifty-nine patients were provided MV 0.5 h (interquartile range: 0.3 to 1.4) post-admission. Clinical and laboratory data before intubation were collected. Using a multivariate logistic regression model, we identified four markers associated with the impending use of MV, including the ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2 ratio), alanine aminotransferase, blood glucose (BG), and lymphocyte counts. Among these markers, SpO 2 /FiO 2 ratio and BG, which can be measured easily and immediately, showed higher accuracy (AUC: 0.88) than SpO 2 /FiO 2 ratio alone (AUC: 0.84), despite no significant difference (DeLong test: P = 0.591). Moreover, even in patients without severe respiratory failure (SpO 2 /FiO 2 ratio > 300), BG (> 138 mg/dL) was predictive of MV use. Measuring BG and SpO 2 /FiO 2 ratio may be a simple and versatile new strategy to accurately identify ER patients with COVID-19 at high risk for the imminent need of MV., (© 2023. The Author(s).)

Citrate synthase (CS) catalyzes the reaction that produces citrate and CoA from oxaloacetate and acetyl-CoA in the tricarboxylic acid (TCA) cycle. All TCA cycle enzymes are localized to the mitochondria in the model organism, the red alga Cyanidioschyzon merolae. The biochemical properties of CS have been studied in some eukaryotes, but the biochemical properties of CS in algae, including C. merolae, have not been studied. We then performed the biochemical analysis of CS from C. merolae mitochondria (CmCS4). The results showed that the k cat /K m of CmCS4 for oxaloacetate and acetyl-CoA were higher than those of the cyanobacteria, such as Synechocystis sp. PCC 6803, Microcystis aeruginosa PCC 7806 and Anabaena sp. PCC 7120. Monovalent and divalent cations inhibited CmCS4, and in the presence of KCl, the K m of CmCS4 for oxaloacetate and acetyl-CoA was higher in the presence of MgCl 2 , the K m of CmCS4 for oxaloacetate and acetyl-CoA was higher and k cat lower. However, in the presence of KCl and MgCl 2 , the k cat /K m of CmCS4 was higher than those of the three cyanobacteria species. The high catalytic efficiency of CmCS4 for oxaloacetate and acetyl-CoA may be a factor in the increased carbon flow into the TCA cycle in C. merolae., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Acute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after the peak of the viral load has passed; however, its underlying mechanisms remain unclear. In the present study, analysis of the alveolar tissue injury markers and epithelial cell death markers in patients with COVID-19 revealed that COVID-19-induced ARDS was characterized by alveolar epithelial necrosis at an early disease stage. Serum levels of HMGB-1, one of the DAMPs released from necrotic cells, were also significantly elevated in these patients. Further analysis using a mouse model mimicking COVID-19-induced ARDS showed that the alveolar epithelial cell necrosis involved two forms of programmed necrosis, namely necroptosis, and pyroptosis. Finally, the neutralization of HMGB-1 attenuated alveolar tissue injury in the mouse model. Collectively, necrosis, including necroptosis and pyroptosis, is the predominant form of alveolar epithelial cell death at an early disease stage and subsequent release of DAMPs is a potential driver of COVID-19-induced ARDS., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Bexarotene, a retinoid X receptor (RXR) agonist, is used to treat cutaneous T-cell lymphoma, and drug repositioning research has also been reported, despite warnings of teratogenicity. However, fetal transfer of bexarotene and its effect on rat fetal bone formation have not been examined. In this study, we conducted a detailed teratogenicity and fetal transferability assessment of bexarotene in rats. Repeated administration of bexarotene during pregnancy caused marked fetal atrophy and bone dysplasia. Although fetal transfer was not detectable by dynamic imaging of [ 11 C]bexarotene by means of positron emission tomography, transfer to the fetus was confirmed by using a gamma counter. Similar levels were found in mother and fetus. In addition, we found that bexarotene was accumulated in the placenta. These findings will be useful for the toxicity assessment of bexarotene as well as for drug discovery research targeting RXR agonists, which are expected to have therapeutic effects in various diseases., Competing Interests: The authors declare the following competing financial interest(s): This study was also funded in part by AIBIOS K.K. This funder was not involved in the study design, data collection, analysis, interpretation of data, writing of the article or the decision to submit it for publication. All authors declare no other competing interests., (© 2022 American Chemical Society.)

DNA immunization has been used to study vaccination methods and for production of specific antibodies. The present study aimed to apply DNA immunization to prepare specific IgYs, which react against rabies virus N protein (RV-N) and can be used to research and diagnose rabies virus. The DNA sequence of RV-N was ligated into a pcDNA 3.1 plasmid for constructing pcDNA-N. Eight hens were divided into four groups. Group 1 comprised the control group (non-immunized). In Groups 2, 3, and 4, hens were injected intramuscularly with pcDNA-N (400 µg/hen). Eight injections were administered every other week. From the 4th week, an adjuvant was injected in addition to pcDNA-N. Freund's complete adjuvant (FCA) and λ -carrageenan were administered to Groups 3 and 4, respectively. Eggs were collected daily, and the specific antibody activities of egg yolks were measured by ELISA. IgYs were purified from pooled egg yolks at 16-19 weeks post-administration in each group. The detection sensitivities of the RV-N were compared using purified IgY as the primary antibody for ELISA, dot blotting, and western blotting. Egg yolks from one of the two hens in Group 2 (pcDNA-N alone) and all hens in Groups 3 (pcDNA-N + FCA) and 4 (pcDNA-N + λ Carra) had increased ELISA values. The combined use of λ -carrageen in DNA immunization resulted in an adjuvant effect comparable to that of FCA. Each purified specific IgY detected RV-N in the ELISA, western blotting, and dot blotting; however, the detection sensitivity differed. Higher detection sensitivity of the + λ Carra IgY was observed by ELISA, whereas there was higher detection sensitivity of +FCA IgY in western blotting and dot blotting. In summary, anti-rabies virus N protein IgY was prepared through DNA immunization of hens using FCA or λ -carrageenan as adjuvants and can be used as a primary antibody to detect rabies viruses., (2022, Japan Poultry Science Association.)

Background: To evaluate the efficacy and safety of intra-articular injection of diclofenac etalhyaluronate (DF-HA) in patients with osteoarthritis (OA) of the hip, ankle, shoulder, or elbow., Methods: In this randomized, placebo-controlled, double-blind study in Japan, Japanese patients aged ≥20 years diagnosed with OA of the hip, ankle, shoulder, or elbow were randomly assigned 1:1 to DF-HA 30 mg or placebo (citric acid-sodium citrate buffered solution). Subjects received three injections of the study drug in each joint cavity every 4 weeks and were assessed for 12 weeks after the first injection. The primary endpoint was the mean change from baseline in a diary-based 11-point numerical rating scale (NRS) for pain over 12 weeks, analyzed for each joint. Treatment-emergent adverse events were recorded, and morphological changes in each joint were evaluated radiographically., Results: The study drug (DF-HA vs placebo) was injected into 90, 60, 90, or 50 subjects with OA of the hip, ankle, shoulder, or elbow (46 vs 44, 30 vs 30, 45 vs 45, and 25 vs 25, respectively). The group differences in the mean change from baseline in the pain NRS over 12 weeks were - 0.81 (95% confidence interval: - 1.48 to - 0.13), - 0.07 (- 1.03 to 0.89), 0.15 (- 0.48 to 0.78), and 0.61 (- 0.41 to 1.62) for the hip, ankle, shoulder, and elbow joints, respectively, with statistically significant differences observed only in the hip joint. The change from baseline in the hip joint was greater with DF-HA than placebo at all time points from Weeks 1-12. No clinically significant adverse events or radiographic changes were observed., Conclusions: Intra-articularly administered DF-HA for hip OA produced a rapid response and was safe, with analgesia maintained for 12 weeks when administered every 4 weeks., Trial Registration: JapicCTI-173,678 (First registered date: 21 August 2017)., (© 2022. The Author(s).)