Hiroshima University
  • Hiroshima, Hiroshima, Japan
Recent publications
The Pfizer‐BioNTech coronavirus disease 2019 (COVID‐19) vaccine is extensively used worldwide, and its safety has been proven. Herein, we report a case of an acute necrotic disorder in the small intestine post‐COVID‐19 vaccination. The patient developed severe abdominal pain the day after the first vaccination. Contrast‐enhanced computed tomography showed extensive ileum wall thickening and ascites. Colonoscopy revealed a ring‐shaped ulcer and stricture in the terminal ileum. Ileocecal resection was performed, and the patient did not have further episodes of a necrotic disorder in the small intestine. Although it is unknown if this event is associated with vaccination, and this occurrence also does not outweigh the efficacy and safety of the Pfizer‐BioNTech COVID‐19 vaccine, gastroenterologists need to be aware of this rare case, given its noteworthy timing.
Objectives: Capsule endoscopy (CE) has been shown to have poor diagnostic performance when the capsule passes quickly through the small bowel, especially the proximal jejunum. This study aimed to evaluate the diagnostic yield of proximal jejunal lesions with third-generation CE technology. Methods: We retrospectively examined 138 consecutive patients, 76 (55.0%) of whom were men. The patients' median age was 70 years, and proximal jejunal lesions were detected by CE and/or double-balloon endoscopy at Hiroshima University Hospital between January 2011 and June 2021. We analyzed the diagnostic accuracy of CE for proximal jejunal lesions and compared the characteristics of the discrepancy between the use of CE and double-balloon endoscopy with Pillcam SB 2 (SB2) and Pillcam SB 3 (SB3). Results: SB2 and SB3 were used in 48 (35%) and 90 (65%) patients, respectively. There was no difference in baseline characteristics between these groups. Small-bowel lesions in the proximal jejunum comprised 75 tumors (54%), 50 vascular lesions (36%), and 13 inflammatory lesions (9%). The diagnostic rate was significantly higher in the SB3 group than in the SB2 group for tumors (91% vs. 72%, p < 0.05) and vascular lesions (97% vs. 69%, p < 0.01). For vascular lesions, in particular, the diagnostic rate of angioectasia improved in the SB3 group (100%) compared with that in the SB2 group (69%). Conclusions: SB3 use improved the detection of proximal jejunal tumors and vascular lesions compared with SB2 use.
This chapter introduces the moment-based epistemic uncertainty propagation in Markov models. The epistemic uncertainty in Markov models introduces the uncertainty of model parameters, and it can be propagated by regarding parameters as random variables. The idea behind the moment-based approach is to approximate the multiple integration with a series expansion of model parameters. This leads to the efficient computation of the uncertainty in the expected output measure. The expected output measure is represented by the expected value and the variance of model parameters and the first and second derivatives of output measure with respect to model parameters. In this chapter, we introduce the formulation of moment-based epistemic uncertainty propagation and the concrete methods to obtain the first and second derivatives of output measures in Markov models.
In this study, different assortments of 2-arylquinolines and 2,6-diarylquinolines have been developed. Recently, we have developed a new series of 6,7-dimethoxy-4-alkoxy-2-arylquinolines as Topoisomerase I (TOP1) inhibitors with potent anticancer activity. Utilising the SAR outputs from this study, we tried to enhance anticancer and TOP1 inhibitory activities. Though target quinolines demonstrated potent antiproliferative effect, specifically against colorectal cancer DLD-1 and HCT-116, they showed weak TOP1 inhibition which may be attributable to their non-coplanarity. Thereafter, screening against kinase panel revealed their dual inhibitory activity against EGFR and FAK. Quinolines 6f, 6h, 6i, and 20f were the most potent EGFR inhibitors (IC50s = 25.39, 20.15, 22.36, and 24.81 nM, respectively). Meanwhile, quinolines 6f, 6h, 6i, 16d, and 20f exerted the best FAK inhibition (IC50s = 22.68, 14.25, 18.36, 17.36, and 15.36 nM, respectively). Finally, molecular modelling was employed to justify the promising EGFR/FAK inhibition. The study outcomes afforded the first reported quinolines with potent EGFR/FAK dual inhibition.
Background Sciatic hernias are rare pelvic floor hernias that occur through the sciatic foramen and often present as abdominal or pelvic pain, particularly in women. Historically, they were repaired using an open approach, with limited reports on their laparoscopic treatment. Case presentation Here we present the case of an 85-year-old woman who had repeated abdominal pain and was referred to our hospital for sciatic hernia surgery after conservative treatment. We laparoscopically observed the deep pelvis and identified the right sciatic hernia. When an extraperitoneal space was dissected, an ureterohypogastric nerve fascia (UNF) and a vesicohypogastric fascia (VF) were identified. Moreover, the maneuver to mobilize the fasciae inside from the pelvic wall made it possible to separate the ureter and urinary bladder, which might have otherwise incarcerated in the hernia. We repaired the defect of the sciatic foramen with a mesh plug and patch. The patient had an uneventful recovery, and the absence of sciatic herniation recurrence was confirmed 1 year after surgery. Conclusion A laparoscopic repair of a sciatic hernia could permit detailed non-invasive observations of the deep pelvis and be performed effectively by recognizing an UNF and a VF located near the sciatic foramen.
Background Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo. Methods Three different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated. Results The injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs. Conclusions Our result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs.
The Northeast Japan arc hosts a number of hydrothermal vein‐type copper deposits associated with Neogene felsic intrusions. The Arakawa area is underlain by Cretaceous granites and Tertiary sedimentary rocks, which were intruded by the Miocene Ushizawamata dacite. Zircon grains from the dacite intrusion yield a 206Pb/238U intercept age (laser ablation inductively coupled plasma mass spectrometry) of 8.10 ± 0.30 Ma, consistent with a previously reported K‐Ar illite age (8.1 ± 0.4 Ma) of the Ushizawamata lead and zinc prospect in the Arakawa area. The dacite intrusion and the surrounding Miocene sedimentary rocks were altered by hydrothermal activity on the surface, classified into four alteration zones: (1) biotite‐chlorite, (2) illite, (3) chlorite and (4) smectite, centered on the intrusion. About 20 major vertical sub‐parallel copper‐bearing quartz veins occur in the chlorite alteration zone on the west side of the dacite. The first vein stage is composed of chalcopyrite and chamosite with a minor amount of quartz in brecciated wall rocks, and the second‐stage is characterized by the presence of hematite in addition to the first‐stage mineral assemblage. The third‐stage consists of comb‐shaped quartz veins with a minor amount of chalcopyrite, sphalerite, galena and pyrite, and the fourth‐stage of barite and apatite present in druse in the third‐stage veins. Primary fluid inclusions in quartz of the first‐ and third‐stages are all liquid‐rich and two‐phase. Homogenization temperature and salinity of first‐stage quartz are 263–277°C and 5.7–7.5 wt% NaCl equivalent (eq.); in quartz of the third‐stage, 251–270°C and 2.7–4.2 wt% in the inner zone and 207–250°C and 2.7–3.7 wt% in comb‐shaped quartz on the vein margin. The fluid inclusions in quartz phenocrysts of the Ushizawamata dacite show two distinct assemblages, halite‐bearing polyphase inclusions that coexist with vapor‐phase inclusions and/or vapor‐rich two‐phase inclusions, and liquid‐rich two‐phase inclusions. Homogenization temperature and salinity of the polyphase inclusions are higher than 401°C and 46.7 wt%, respectively, and those of the vapor‐rich two‐phase inclusions report 393–419°C and 2.6–3.7 wt% NaCl, whereas the liquid‐rich two‐phase inclusions returned 344–403°C and 8.0–9.3 wt%, respectively. These results indicate that the ore forming fluid was slightly cooler and lower in salinity than the late‐stage hydrothermal fluid in the Ushizawamata intrusion. The spatial and temporal proximity between the Ushizawamata dacite and the hydrothermal veins indicates that the dacitic magma was genetically related to the vein copper mineralization in the Arakawa area. The Arakawa vein‐type copper deposit located in the Northeast Japan arc is adjacent to dacitic intrusion and both were formed at about 8 Ma. The ore forming fluid that formed the Arakawa deposit caused copper mineralization during the dilution and cooling of the single‐phase fluid of late hydrothermal stage in the dacitic intrusion. The spatial and temporal proximity between the dacite and the hydrothermal veins indicates that the dacitic magma was genetically related to the vein copper mineralization in the Arakawa area.
Oral glucose ingestion induces systemic changes of many blood metabolites related not only to glucose, but also other metabolites such as amino acids and lipids through many blood hormones. However, the detailed temporal changes in the concentrations of comprehensive metabolites and hormones over a long time by oral glucose ingestion are uncharacterized. We measured 83 metabolites and 7 hormones in 20 healthy human subjects in response to glucose ingestion. We characterized temporal patterns of blood molecules by four features: (i) the decomposability into “amplitude” and “rate” components, (ii) the similarity of temporal patterns among individuals, (iii) the relation of molecules over time among individuals, and (iv) the similarity of temporal patterns among molecules. Glucose and glucose metabolism-related hormones indicated a rapid increase, and citrulline and lipids, which indicated a rapid decrease, returned to fasting levels faster than amino acids. Compared to glucose metabolism-related molecules and lipids, amino acids showed similar temporal patterns among individuals. The four features of temporal patterns of blood molecules by oral glucose ingestion characterize the differences among individuals and among molecules.
Background Spontaneous rupture of a hemorrhagic hepatic cyst is extremely rare. There is no standard treatment recommended for this condition. We report two cases of hemorrhagic hepatic cysts that spontaneously ruptured and were successfully treated with laparoscopic deroofing. We review the literature and discuss the characteristic features of spontaneous rupture of hemorrhagic hepatic cysts and their treatment. Case presentation The first patient was an 85-year-old man admitted for sudden-onset right hypochondralgia and fever. Computed tomography revealed a 13-cm hepatic cyst occupying the right lobe of the liver and spontaneous rupture of the cyst. Laparoscopic deroofing was performed and continuous oozing from the cystic wall was found. Histological examination revealed a simple hepatic cyst. The patient was discharged on postoperative day 6. In the second case, a 77-year-old woman who had been followed up for a simple hepatic cyst (13 cm) was admitted for sudden onset of right hypochondralgia. Computed tomography demonstrated a 9.9-cm hepatic cyst occupying segment 4 of the liver. Laparoscopic deroofing was performed and continuous oozing from the cystic wall was observed. Histological examination revealed a simple hepatic cyst. The patient was discharged on postoperative day 6. Conclusion Laparoscopic deroofing was performed in patients with spontaneous rupture of hemorrhagic nonparasitic hepatic cysts.
Purpose A distal femoral trial component was manufactured, and flexion gap size and inclination were evaluated with or without the distal femoral trial component in total knee arthroplasty (TKA). This study aimed to evaluate the effect of the distal femoral trial component on flexion gap size and joint inclination in posterior-stabilized (PS)-TKA. Materials and methods A total of 84 patients with medial osteoarthritis who underwent mobile-bearing PS-TKA using modified gap techniques were included in this retrospective study. The flexion gap size and inclination before and after setting the distal femoral trial component were evaluated and compared with the final gap size and inclination. Results The joint gap size and inclination were significantly lower in those with than in those without the distal femoral trial component ( P = 0.005, P < 0.001). The final gap size and inclination were similar to the gap size and inclination with the distal trial component ( P = 0.468, P = 0.158). Conclusions The joint gap size and medial tension in PS-TKA were significantly reduced after setting the distal femoral trial component. The flexion gap measured using the distal femoral trial component was similar to that when the final trial component was set. To more accurately perform the gap technique TKA, the flexion gap should be measured using the distal femoral trial component.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by specific social symptoms, restricted interests, stereotyped repetitive behaviors, and delayed language development. The 3q29 microdeletion (3q29del), a recurrent copy number variant, confers a high risk for ASD and schizophrenia, and serves as an important pathological model for investigating the molecular pathogenesis of a large number of neurodevelopmental and psychiatric conditions. Recently, mouse models carrying a deletion of the chromosomal region corresponding to the human 3q29 region (Df/+ mice) were generated and demonstrated neurodevelopmental and psychiatric conditions associated behavioral abnormalities, pointing to the relevance of Df/+ mice as a model for these conditions with high construct and face validity. Currently, the molecular pathogenesis of these behavioral phenotypes in Df/+ mice remains unclear. The oxytocin (OXT) system plays a central role in social behavior across species and has a potential role in ASD. In this study, to elucidate the molecular mechanisms behind impaired social behavior in Df/+ mice, we investigated the possible involvement of OXT signaling in impaired social behavior in Df/+ mice. We demonstrated that OXT administration restored the impaired social behavior in Df/+ mice. We also demonstrated that the number of OXT-positive cells in the paraventricular nucleus (PVN) was significantly lower in Df/+ mice than in wild-type (WT) littermates. Consistent with this, the level of OXT peptide in the cerebral cortex of Df/+ mice was lower than in WT littermates. Our study may provide important insights into the molecular pathophysiological basis of neurodevelopmental and psychiatric conditions, including ASD.
Extension concept mapping is a technique to connect prior existing concept maps with new knowledge structures. It offers advantages in each stage of the knowledge-integrating process and encourages learners to improve their performance. While previous studies have confirmed that the extended kit-build concept map outperformed the extended scratch-build approach in terms of comprehension test scores and map size, they have yet to evaluate the quality of concept maps and students' perceptions. Although the size of the concept map components could represent the breadth of personal knowledge, it does not constantly describe the good knowledge structure. In addition, the student's degree of acceptance after the concept mapping demonstrates their intention to use systems in the future. The present study aims to compare the effect of extended scratch-build and extended kit-build on the students' quality of knowledge structures and perceptions. Fifty-five second-year university students were involved and divided into two groups: control and experimental. The control group utilized the extended scratch-build map, while the experimental group used the extended kit-build concept mapping tool. Quality of propositions and structural map scores as learning outcomes were used to measure the students' knowledge structures. The possibility of a relationship between quality scores was expressed using the Spearman correlation. This study involved the Technology Acceptance Model to confirm the students' perceptions of extension concept mapping tools. The perceived ease-of-use, perceived usefulness, and behavioral intention constructs were used to investigate users' intentions. The findings suggest that the quality of propositions and structural map scores in the experimental group were significantly higher than in the control group. This study also found that the extended kit-build method achieved better perceptions scores than the extended scratch-build.
Background Phlebitis is an important complication occurring in patients with peripheral intravascular catheters (PIVCs). The risk factors for phlebitis in the intensive care unit (ICU) was examined. Methods A secondary analysis of a prospective multicenter cohort study was conducted, involving 23 ICUs in Japan—the AMOR–VENUS study. Consecutive patients aged ≥ 18 years admitted to the ICU with newly inserted PIVCs after ICU admission were enrolled. Characteristics of the ICU, patients, PIVCs, and the drugs administered via PIVCs were recorded. A marginal Cox regression model was used to identify the risk factors associated with phlebitis. Results A total of 2741 consecutive patients from 23 ICUs were reviewed for eligibility, resulting in 1359 patients and 3429 PIVCs being included in the analysis population. The median dwell time was 46.2 h (95% confidence interval [CI], 21.3–82.9). Phlebitis occurred in 9.1% (95% CI, 8.2–10.1%) of catheters (3.5 cases/100 catheter days). The multivariate analysis revealed that the only factors that increased the risk of developing phlebitis were drugs administered intravenously. This study included 26 drugs, and 4 were associated with increased phlebitis: nicardipine (HR, 1.85; 95% CI, 1.29–2.66), noradrenaline (HR, 2.42; 95% CI, 1.40–4.20), amiodarone (HR, 3.67; 95% CI, 1.75–7.71) and levetiracetam (HR, 5.65; 95% CI, 2.80–11.4). Alternatively, factors significantly associated with a reduced risk of phlebitis were: standardized drug administration measures in the ICU (HR, 0.35; 95% CI, 0.17–0.76), 30≤ BMI (HR, 0.43; 95% CI, 0.20–0.95), catheter inserted by a doctor as nurse reference (HR, 0.55; 95% CI, 0.32–0.94), and upper arm insertion site as forearm reference (HR, 0.52; 95% CI, 0.32–0.85). The nitroglycerin was associated with a reduced phlebitis risk (HR, 0.22; 95% CI, 0.05–0.92). Conclusion Various factors are involved in the development of phlebitis caused by PIVCs in critically ill patients, including institutional, patient, catheter, and drug-induced factors, indicating the need for appropriate device selection or models of care in the ICU. Trial registration: UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019, July 1, 2017).
Background Occlusion or malposition of the venous cannula during cardiopulmonary bypass (CPB) increases central venous pressure (CVP). When high CVP is measured, we need to determine if it is actually high or if it is measured due to catheter occlusion or technical problems with the measurement. Case presentation We experienced a case of excessively high CVP due to malposition of the venous cannula during CPB. A 78-year-old woman underwent an aortic arch replacement for acute aortic dissection. During CPB, CVP increased up to 78 mmHg, and the time above 50 mmHg was 48 min. In this case, ultrasonography of the internal jugular vein (IJV) was useful to confirm high CVP. Conclusions Ultrasonography is now a familiar diagnostic tool and can be used at any time. We should consider ultrasonography as the first choice for diagnosing the cause of high CVP during CPB.
Background Hepatitis B virus (HBV) infection is one of the major public health problems globally as well as in Cambodia. Continuous information on HBV infection burden is required to implement effective disease control strategies. This study aimed to determine the prevalence and genotype distribution of HBV infection in Cambodia through a systematic review with meta-analysis. Methods Four databases (PubMed, Web of Science, Scopus, and Google Scholar) were used to search published studies reporting either HBV prevalence or genotype distribution in Cambodia until August 21, 2020. Reviews, modeling studies, and studies conducted among Cambodian permanently living abroad were excluded. The Freeman–Tukey double arcsine transformation was implemented to achieve approximate normality. The DerSimonian and Laird method was used to compute pooled estimates based on the transformed values and their variance. Possible publication bias was assessed by the Egger test and the funnel plot. Results A total of 22 studies were included, covering 22,323 people. Ten studies reported HBV prevalence in the general population. The HBV infection prevalence was 4.73% (95%CI: 2.75–7.17%) in the general population and 19.87% (95%CI: 10.95–30.63%) in high-risk/co-infected groups. By sub-group analysis, the prevalence was 6.81% (95% CI: 4.43–9.66) in adults older than 15 years old, 2.37% (95% CI:0.04–7.05) in children 6–15 years old, and 2.47% (95% CI: 0.96–4.59) in children less than five years old. The prevalence of HBV infection decreased over time. Predominant HBV genotypes were genotypes C and B with 82.96% and 16.79%, respectively. Conclusions The decrease in HBV infection prevalence in Cambodia demonstrates the effects of national hepatitis B immunization, improved clinical hygiene, and the use of disposable devices. However, the estimated HBV prevalence among the general population indicates an intermediate endemicity level of HBV infection. Therefore, population screening and linkage to care, high vaccination coverage, health promotion, and HBV surveillance are essential to meet the WHO 2030 goal.
We conduct frictional experiments using cuttings collected at Nankai Trough IODP Site C0002 over 980.5–3262.5 mbsf (meters below seafloor) depth interval to better understand the frictional properties through the accretionary prism. The experiments are conducted at the in situ effective normal stresses (9–37 MPa) under brine-saturated conditions, and the slip velocity is abruptly changed in a stepwise manner to either of 0.3, 3, or 33 µm/s after the steady-state friction is reached. The friction coefficient ( μ ) of the cuttings samples ranges from 0.45 to 0.60, with a slight increase in μ with increasing depth, related to decreasing smectite content. The velocity dependence of friction ( a − b ) is positive at all depths and ranges from 0.001 to 0.006, which indicates a velocity-strengthening behavior; these values are consistent with relatively homogeneous deformation microstructures. The critical slip distance ( D c ) ranges from 0.5 to 123 μm, with relatively large values obtained for the smectite-rich samples. The changes in both the friction coefficient and rate- and state-friction parameters are likely associated with mineralogical change and consolidation with increasing depth. Although all of the cuttings samples collected from Site C0002 exhibit a velocity-strengthening behavior, a slight decreasing trend in a − b with increasing depth indicates either a nearly neutral velocity dependence or a possible transition to velocity-weakening behavior at greater depths, which may be attributed to the occurrence of slow earthquakes in the Nankai accretionary prism.
Transmembrane protein 16A (TMEM16A) forms a plasma membrane-localized Ca ²⁺ -activated Cl- channel. Its gene has been mapped to an area on chromosome 11q13, which is amplified in head and neck squamous cell carcinoma (HNSCC). In HNSCC, TMEM16A overexpression is associated with not only high tumor grade, metastasis, low survival, and poor prognosis, but also deterioration of clinical outcomes following platinum-based chemotherapy. Recent study revealed the interaction between TMEM16A and transforming growth factor-β (TGF-β) has an indirect crosstalk in clarifying the mechanism of TMEM16A-induced epithelial-mesenchymal transition. Moreover, human papillomavirus (HPV) infection can modulate TMEM16A expression along with epidermal growth factor receptor (EGFR), whose phosphorylation has been reported as a potential co-biomarker of HPV-positive cancers. Considering that EGFR forms a functional complex with TMEM16A and is a co-biomarker of HPV, there may be crosstalk between TMEM16A expression and HPV-induced HNSCC. EGFR activation can induce programmed death ligand 1 (PD-L1) synthesis via activation of the nuclear factor kappa B pathway and JAK/STAT3 pathway. Here, we describe an interplay among EGFR, PD-L1, and TMEM16A. Combination therapy using TMEM16A and PD-L1 inhibitors may improve the survival rate of HNSCC patients, especially those resistant to anti-EGFR inhibitor treatment. To the best of our knowledge, this is the first review to propose a biological validation that combines immune checkpoint inhibition with TMEM16A inhibition.
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3,660 members
Hidetoshi Tahara
  • Department of Cellular and Molecular Biology
Kazuaki Tanabe
  • Department of Gastroenterological and Transplant Surgery
Junyi Zhang
  • Graduate School of Advanced Science and Engineering; Graduate School for International Development and Cooperation
Wakasugi Yuta
  • Graduate School of Advanced Science and Engineering
1-3-2 Kagamiyama, 739-8511, Hiroshima, Hiroshima, Japan