1,604 results on '"Horie A"'
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2. Combination of risk alleles of PNPLA3, TM6SF2, and HSD17B13 of donors can predict recurrence of steatotic liver disease after liver transplantation.
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Makino, Kenta, Ishii, Takamichi, Ogiso, Satoshi, Nakakura, Akiyoshi, Nishio, Takahiro, Fukumitsu, Ken, Uebayashi, Elena Yukie, Munekage, Fumiaki, Horie, Hiroshi, Iwaki, Kentaro, Ito, Takashi, and Hatano, Etsuro more...
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GENETIC risk score ,NON-alcoholic fatty liver disease ,SINGLE nucleotide polymorphisms ,LIVER diseases ,FATTY liver - Abstract
Aims: This study aimed to identify the genetic risk factors from donors or recipients that contribute to postliver transplantation (LT) steatotic liver disease (SLD), focusing on the genetic risk score (GRS) based on single nucleotide polymorphisms (SNPs) in SLD patients. Methods: This retrospective study included 55 Japanese SLD recipients and their respective donors. Genotyping of PNPLA3, TM6SF2, and HSD17B13 was undertaken, and the combined GRS was calculated. The relationship between the GRS and the incidence of posttransplant SLD was also evaluated. Results: The SLD recipients had a high prevalence of post‐LT graft steatosis/steatohepatitis (76.4% and 58.2%, respectively). Although the recipients had a high frequency of risk alleles, there was no relationship between the number of risk alleles for each SNP and the incidence of posttransplant SLD. In contrast, an increased number of risk alleles for any SNP in the donor was correlated with high incidence rates of both post‐LT steatosis and steatohepatitis. A multivariable analysis showed that a high donor GRS was an independent risk factor for graft steatosis (odds ratio 8.77; 95% CI, 1.94–52.94; p = 0.009). Similarly, a high donor GRS was an independent risk factor (odds ratio 6.76; 95% CI, 1.84–30.78; p = 0.007) for post‐LT graft steatohepatitis. Conclusions: Donor risk alleles of PNPLA3, TM6SF2, and HSD17B13, rather than recipient risk alleles, have been implicated in the development of posttransplant SLD. The combination of these donor risk alleles into a GRS could predict the development of posttransplant SLD. [ABSTRACT FROM AUTHOR] more...
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- 2024
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3. APRIL/BAFF upregulation is associated with clonal B‐cell expansion in Hunner‐type interstitial cystitis.
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Horie, Masafumi, Akiyama, Yoshiyuki, Katoh, Hiroto, Taguchi, Satoru, Nakamura, Masaki, Mizuguchi, Keishi, Ito, Yukinobu, Matsushita, Takashi, Ushiku, Tetsuo, Ishikawa, Shumpei, Goto, Akiteru, Kume, Haruki, Homma, Yukio, and Maeda, Daichi more...
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RNA sequencing ,PLASMA cells ,TUMOR necrosis factors ,RECOMBINANT proteins ,TUMOR proteins - Abstract
Hunner‐type interstitial cystitis (HIC) is a chronic inflammatory disease of the urinary bladder with an unknown etiology. We conducted comprehensive immunogenomic profiling of bladder specimens obtained by biopsy and cystectomy from 37 patients with HIC. Next‐generation RNA sequencing demonstrated abundant plasma cell infiltration with frequent light chain restriction in HIC‐affected bladder tissue. Subsequent analysis of the B‐cell receptor repertoire revealed spatial and temporal expansion of B‐cell clones. The extent of B‐cell clonal expansion was significantly correlated with the gene expression levels of TNFSF13 and TNFSF13B, which encode APRIL and BAFF, respectively. These findings indicate that APRIL and BAFF are the key regulators of clonal B‐cell expansion in HIC and might serve as therapeutic targets in this debilitating disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR] more...
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- 2024
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4. Efficacy of immune checkpoint inhibitors according to programmed cell death‐ligand 1 expression in patients with non‐small cell lung cancer and brain metastasis: A real‐world prospective observational study.
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Masuda, Takeshi, Tsubata, Yukari, Hata, Kojirou, Horie, Mika, Kiura, Katsuyuki, Kanaji, Nobuhiro, Inoue, Takuya, Kodani, Masahiro, Yanai, Masaaki, Yamaguchi, Kakuhiro, Matsumoto, Naoko, Yamasaki, Masahiro, Ishikawa, Nobuhisa, Masuda, Ken, Takigawa, Nagio, Kuyama, Shoichi, Kubota, Tetsuya, Nishii, Kazuya, Hotta, Katsuyuki, and Hattori, Noboru more...
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PROGRAMMED death-ligand 1 ,SCIENTIFIC observation ,CANCER patients ,DESCRIPTIVE statistics ,IMMUNE checkpoint inhibitors ,GENE expression ,METASTASIS ,LONGITUDINAL method ,CANCER chemotherapy ,DRUG efficacy ,LUNG cancer ,CONFIDENCE intervals ,BRAIN tumors ,OVERALL survival ,PROPORTIONAL hazards models - Abstract
Introduction: Studies have shown the antitumor efficacy of immune checkpoint inhibitors (ICI) in patients with non‐small cell lung cancer (NSCLC) and brain metastases (BM). However, it is unclear whether the efficacy of ICI is similar between patients with and without BM. It is yet unclear whether the efficacy of ICI in patients with BM increases with higher levels of programmed cell death‐ligand 1 (PD‐L1) expression, as observed in patients without BM. Methods: We compared the outcomes of ICI treatment between patients with and without BM using a cohort containing 1741 prospectively enrolled patients with lung cancer. We investigated whether there were differences in the outcomes of ICI based on PD‐L1 expression levels between these patients. Results: We enrolled 240 patients with NSCLC with or without BM who were treated with ICI or both chemotherapy and ICI. There were no significant differences in overall survival (OS) between all patients with or without BM (p = 0.489). However, OS was significantly shorter in patients with BM than in those without in the PD‐L1 ≥ 50% group (16.5 M vs. 30.6 M, p = 0.003) but not in the PD‐L1 ≥ 1% or negative group. BM was an independent poor prognostic factor for OS (hazard ratio: [95% confidence interval], 2.045; [1.058–3.953], p = 0.033) in the PD‐L1 ≥ 50% group. Conclusion: Our study indicated that the outcomes of patients with or without BM treated with ICI were not significantly different. The efficacy of ICI in patients with PD‐L1 expression ≥50% would be lower in patients with BM than in those without. [ABSTRACT FROM AUTHOR] more...
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- 2024
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5. Vaginal Cuff Infection Caused by Ureaplasma parvum After Hysterectomy for Uterine Cervical Cancer: A Case Report.
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Chikamatsu, Hayato, Taki, Mana, Kitamura, Sachiko, Sunada, Masumi, Yamanoi, Koji, Murakami, Ryusuke, Yamaguchi, Ken, Horie, Akihito, Tsuchido, Yasuhiro, Hamanishi, Junzo, Mandai, Masaki, and Cui, Dawei more...
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CERVICAL cancer ,VAGINAL hysterectomy ,PREMATURE labor ,AMNIOTIC liquid ,POLYMERASE chain reaction - Abstract
Ureaplasma parvum is one of the most common endemic mycoplasmas in the genitourinary tract and can cause amniotic fluid infection leading to preterm labor. We report a rare case of Ureaplasma parvum infection ascending from the vagina to the abdominal cavity after hysterectomy, causing vaginal cuff infection, postoperative peritonitis, and small bowel obstruction. A 29‐year‐old nulliparous woman presented with infected uterine cervical cancer. After radical hysterectomy for uterine cervical cancer, the patient had paralytic ileus with ascites and fever. Peritonitis was suspected; however, all cultures were negative, making it difficult to identify the causative organism. Polymerase chain reaction (PCR) of the ascites revealed Ureaplasma parvum, which could be treated with levofloxacin (LVFX). Open drainage to control the infection revealed a necrotic tissue around vaginal cuff and the small intestine encased in cocoon‐like fibers like sclerosing encapsulating peritonitis. After the infection was improved, the bowel obstruction was also improved. Ureaplasma spp. can be difficult to culture. PCR testing for Ureaplasma infection should be considered when urogenital infection is suspected in patients prone to opportunistic infections, such as those with malignant tumors. [ABSTRACT FROM AUTHOR] more...
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- 2024
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6. Association between adenomyosis and placenta accreta and mediation effect of assisted reproductive technology on the association: A nationwide observational study.
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Wada, Yoshimitsu, Takahashi, Hironori, Ogoyama, Manabu, Horie, Kenji, Suzuki, Hirotada, Usui, Rie, Jwa, Seung Chik, Ohkuchi, Akihide, and Fujiwara, Hiroyuki
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- 2024
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7. Three‐year outcomes of contemporary endovascular treatment in over 25‐cm femoropopliteal artery disease from a retrospective multicenter registry: A retrospective observational study.
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Horie, Kazunori, Takahara, Mitsuyoshi, Nakama, Tatsuya, Tanaka, Akiko, Tobita, Kazuki, Hayakawa, Naoki, Mori, Shinsuke, Iwata, Yo, and Suzuki, Kenji
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- 2024
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8. Structural Basis for Histaminergic Regulation of Neural Circuits in the Mouse Olfactory Bulb.
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Minami‐Ogawa, Yukari, Kiyokage, Emi, Yamanishi, Haruyo, Horie, Sawa, Ichikawa, Satoshi, and Toida, Kazunori
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Odor information is modulated by centrifugal inputs from other brain regions to the olfactory bulb (OB). Neurons containing monoamines, such as serotonin, acetylcholine, and noradrenaline, are well known as centrifugal inputs; however, the role of histamine, which is also present in the OB, is not well understood. In this study, we examined the histaminergic neurons projecting from the hypothalamus to the OB. We used an antibody against histidine decarboxylase (HDC), a synthesizing enzyme of histamine, to identify histaminergic neurons and assess their localization within the OB and the ultrastructure of their fibers and synapses using multiple immunostaining laser microscopy, ultra‐high voltage electron microscopy (EM), and EM to confirm their relationships with other neurons. To further identify the origin nucleus of the histaminergic neurons projecting to the OB, we injected the retrograde tracer FluoroGold and analyzed the pathway to the OB anterogradely. HDC‐immunoreactive (‐ir) fibers were abundant in the olfactory nerve (ON) layer compared to other monoamines. HDC‐ir neurons received asymmetrical synapses from ONs and formed synapses containing pleomorphic vesicles with variable postsynaptic densities to non‐ON elements, thus forming serial synapses. We also confirmed that histaminergic neurons project from the rostral ventral tuberomammillary nucleus to the granule cell layer of the OB and, for the first time, successfully visualized their axons from the hypothalamus to the OB. These findings indicate that histamine may regulate odor discrimination in the OB, suggesting a regulatory relationship between hypothalamic function and olfaction. We thus elucidate morphological mechanisms with tuberomammillary nucleus–derived histaminergic neurons involved in olfactory information. [ABSTRACT FROM AUTHOR] more...
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- 2024
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9. Arterial Spin Labeling‐Based MR Angiography for Cerebrovascular Diseases: Principles and Clinical Applications.
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Togao, Osamu, Obara, Makoto, Yamashita, Koji, Kikuchi, Kazufumi, Wada, Tatsuhiro, Murazaki, Hiroo, Arimura, Koichi, Nishimura, Ataru, Horie, Nobutaka, van de Ven, Kim, Van Cauteren, Marc, and Ishigami, Kousei more...
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MAGNETIC resonance angiography ,DIGITAL subtraction angiography ,CEREBRAL angiography ,BRAIN imaging ,PERFUSION imaging - Abstract
Arterial spin labeling (ASL) is a noninvasive imaging technique that labels the proton spins in arterial blood and uses them as endogenous tracers. Brain perfusion imaging with ASL is becoming increasingly common in clinical practice, and clinical applications of ASL for intracranial magnetic resonance angiography (MRA) have also been demonstrated. Unlike computed tomography (CT) angiography and cerebral angiography, ASL‐based MRA does not require contrast agents. ASL‐based MRA overcomes most of the disadvantages of time‐of‐flight (TOF) MRA. Several schemes have been developed for ASL‐based MRA; the most common method has been pulsed ASL, but more recently pseudo‐continuous ASL, which provides a higher signal‐to‐noise ratio (SNR), has been used more frequently. New methods that have been developed include direct intracranial labeling methods such as velocity‐selective ASL and acceleration‐selective ASL. MRA using an extremely short echo time (eg, silent MRA) or ultrashort echo‐time (TE) MRA can suppress metal susceptibility artifacts and is ideal for patients with a metallic device implanted in a cerebral vessel. Vessel‐selective 4D ASL MRA can provide digital subtraction angiography (DSA)‐like images. This review highlights the principles, clinical applications, and characteristics of various ASL‐based MRA techniques. Level of Evidence: 5 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR] more...
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- 2024
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10. Predicting continuous amyloid PET values with CSF tau phosphorylation occupancies.
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Wisch, Julie K., Gordon, Brian A., Barthélemy, Nicolas R., Horie, Kanta, Henson, Rachel L., He, Yingxin, Flores, Shaney, Benzinger, Tammie L. S., Morris, John C., Bateman, Randall J., Ances, Beau M., and Schindler, Suzanne E. more...
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- 2024
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11. Confined placental mosaicism with trisomy 13 complicated by severe preeclampsia: A case report and literature review.
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Ito, Takaaki, Takahashi, Hironori, Horie, Kenji, Nagayama, Shiho, Ogoyama, Manabu, and Fujiwara, Hiroyuki
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PREECLAMPSIA diagnosis ,PROTEINURIA ,CHORIONIC villus sampling ,FETAL growth retardation ,SECOND trimester of pregnancy ,CHROMOSOME abnormalities ,PRENATAL diagnosis ,FETAL ultrasonic imaging ,KARYOTYPES ,HYPERTENSION in pregnancy ,MOSAICISM ,AMNIOCENTESIS - Abstract
A 31‐year‐old primiparous woman underwent non‐invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t‐statistics (Z‐score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development. [ABSTRACT FROM AUTHOR] more...
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- 2024
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12. Investigation of the clinical implications of anterior cervical invasion in locally advanced cervical squamous cell carcinoma.
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Tamura, Saya, Yamanoi, Koji, Inayama, Yoshihide, Kurata, Yasuhisa, Himoto, Yuki, Taki, Mana, Murakami, Ryusuke, Horie, Akihito, Yamaguchi, Ken, Hamanishi, Junzo, and Mandai, Masaki
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SQUAMOUS cell carcinoma ,RISK assessment ,CANCER invasiveness ,RESEARCH funding ,CANCER relapse ,MAGNETIC resonance imaging ,DESCRIPTIVE statistics ,CANCER chemotherapy ,COMBINED modality therapy ,CERVICAL cancer ,OVERALL survival ,DISEASE risk factors - Abstract
Purposes: This study investigates the clinical significance of the anterior parametrical invasion in surgically treated patients with cervical squamous cell carcinoma (SCC). Methods: We included patients diagnosed with cervical SCC with local lesions classified as T2b, who were treated at our department between January 2006 and December 2020. We evaluated the degree of anterior invasion using pretreatment magnetic resonance imaging and divided patients into three groups: partial, equivocal, and full invasion. The frequency of recurrence within 3 years (early recurrence) and overall prognosis were assessed. Results: There were 12, 24, and 46 cases in the partial equivocal, and full invasion groups, respectively. Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy was the mainstay of treatment across all groups (7, 17, and 27 cases, respectively). Although the frequency of early recurrence tended to be worse in the full group (partial; 2/7 cases, equivocal; 3/17 cases and full; 9/27 cases), all early local recurrence cases in the full group (four cases) responded well to the subsequent treatment. As for overall survival, the full invasion group had the best prognosis among the three groups. Conclusions: In surgical treatment, although full anterior invasion may increase the risk of early local recurrence, it was considered to have little prognostic impact. [ABSTRACT FROM AUTHOR] more...
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- 2024
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13. CFD Analysis of Laminar Mixing Mechanism and Performance in an Oscillatory Baffled Reactor.
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Murotani, Ryosuke, Horie, Takafumi, Fujioka, Satoko, Komoda, Yoshiyuki, Ohmura, Naoto, Masuda, Hayato, Okita, Erika, and Yasuda, Masahiro
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REYNOLDS number , *COMPUTATIONAL fluid dynamics , *TUBULAR reactors , *FLUID flow , *RADIAL flow - Abstract
The mixing mechanism in an oscillatory baffled reactor (OBR) at the low oscillatory Reynolds number was analyzed using numerical simulation. OBR is a tubular reactor in which baffles are placed at equal intervals, and the interaction between the baffles and oscillatory flow mixes the fluid. At the low oscillatory Reynolds number, mixing induced by the folding and stretching of the fluid was observed at each baffle section. This was caused by the radial flow in the vicinity of the baffles when the direction of the oscillatory flow was reversed. The mixing performance was quantified by applying virtual particle tracing, setting up a virtual boundary surface, and following the changes in its area over time. The area increased exponentially, confirming the chaotic mixing characteristics. [ABSTRACT FROM AUTHOR] more...
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- 2024
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14. A novel variant in IFT122 associated with a severe phenotype of cranioectodermal dysplasia.
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Nagayama, Shiho, Takahashi, Hironori, Hasegawa, Fuyuki, Hori, Asuka, Kizami, Sho, Furukawa, Rieko, Horie, Kenji, Ogoyama, Manabu, Hata, Kenichiro, and Fujiwara, Hiroyuki
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DYSPLASIA ,PHENOTYPES ,GENETIC variation ,UMBILICAL cord ,SKELETAL dysplasia - Abstract
A 27‐year‐old multiparous woman conceived her fetus naturally. Early second‐trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy was artificially terminated at 19 weeks of gestation because of the abnormalities based on the parents' wishes. The parents desired whole‐exome sequencing to detect a causative gene using the umbilical cord and the parents' saliva. Compound heterozygous variants (NC_000003.11(NM_052989.3):c.230 T > G/NC_000003.11(NM_052985.4):c.1178A > T) were identified. We described a fetus with a novel compound heterozygous variant in IFT122. The phenotype of this case was severer than of other types of cranioectodermal dysplasia. [ABSTRACT FROM AUTHOR] more...
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- 2024
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15. Increased Nectin‐4 expression in atopic dermatitis and psoriasis: a preliminary study.
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Nakajima, Kaori, Takemura, Akari, Horie, Akihiro, Tanaka, Miho, Komaki, Reo, Okano, Tatsuro, Takeuchi, Sora, Watabe, Hidenori, Kadono, Takafumi, and Miyagaki, Tomomitsu
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WILCOXON signed-rank test ,KERATINOCYTE differentiation ,BLOOD proteins ,ANTIBODY-drug conjugates ,ATOPIC dermatitis ,OVARIAN cancer ,CELL adhesion molecules - Abstract
The study explores the increased expression of Nectin-4 in patients with atopic dermatitis (AD) and psoriasis vulgaris (PsV). Serum Nectin-4 levels were found to be higher in AD and PsV patients compared to healthy individuals, and correlated with disease severity markers. The study suggests a possible association between Nectin-4 expression and keratinocyte differentiation in inflammatory skin diseases, highlighting the potential role of Nectin-4 in disease progression. Further research with larger sample sizes is needed to validate these findings. [Extracted from the article] more...
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- 2024
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16. High‐Intensity Circular Dichroism of Head‐To‐Tail Regioregular Poly(1,4‐Phenylene)s in the Aggregated State.
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Tanaka, Rikuya, Yamaoka, Seiha, Ikeda, Shuichi, Okano, Kentaro, Horie, Masaki, Minami, Hideto, Suzuki, Nozomu, and Mori, Atsunori
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CIRCULAR dichroism ,LIVING polymerization ,DEGREE of polymerization ,DEPENDENCY (Psychology) ,DIPHOSPHINE - Abstract
Circular dichroism (CD) studies on poly(1,4‐phenylene)s bearing a chiral side chain in the aggregated conditions were carried out. Little CD was observed in a solution form, while addition of a poor solvent into the polyphenylene solution induced aggregation and a strong CD was observed, accordingly. Applying the controlled degree of polymerization (DP) of poly(1,4‐phenylene) in the use of bidentate diphosphine Chiraphos as a ligand for the nickel catalyst, the relationship of DP with CD strength was studied to reveal to show the highest CD at the DP=84 (gabs=ca. 2×10−2). It was also found that the related aggregation was observed in good solvent 1,2‐dichloroethane upon standing the solution at 4 °C for 3–23 days to observe gabs=ca. 10−1. Studies on the substituent effect of poly(1,4‐phenylene) suggested that CD behaviors were dependent on the type of non‐chiral substituent on the aromatic ring as well as the side‐chain chirality. [ABSTRACT FROM AUTHOR] more...
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- 2024
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17. Impact of renal dysfunction on the diagnosis of acute pancreatitis using urinary trypsinogen‐2: A retrospective study.
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Sato, Yuko, Inokuchi, Ryota, Yamamoto, Miyuki, Horie, Ryohei, Asada, Toshifumi, Matsubara, Takehiro, and Doi, Kent
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KIDNEY diseases ,BLOOD urea nitrogen ,PANCREATITIS ,GLOMERULAR filtration rate ,KIDNEY physiology - Abstract
Aim: Early diagnosis of acute pancreatitis is crucial, and urinary trypsinogen has been recently reported as a useful biomarker for diagnosing acute pancreatitis. We aimed to evaluate the impact of renal dysfunction on the diagnostic performance of urinary trypsinogen‐2 for acute pancreatitis. Methods: We conducted a retrospective study using the clinical data of patients who visited the Department of Emergency and Critical Care at the University of Tokyo Hospital between 1 October, 2021, and 30 June, 2022. Patients with available data on qualitative urinary trypsinogen‐2 levels were identified. We compared the urinary trypsinogen‐2 levels among patients who were clinically diagnosed with acute pancreatitis. We further stratified the patients according to renal function parameters, such as serum creatinine level, blood urea nitrogen level, and estimated glomerular filtration rate, and evaluated the performance of urinary trypsinogen‐2 as a biomarker for acute pancreatitis. Results: Within 9 months, 35 patients were identified. Of them, 22 patients showed positive results and 13 showed negative results on the urinary trypsinogen‐2 test. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.80, 0.40, 0.18, and 0.92, respectively. Based on the blood urea nitrogen level and estimated glomerular filtration rate, the prevalence of false‐positive results was significantly higher in patients with reduced renal function than in those with normal renal function. Conclusion: In patients with reduced renal function, the urinary trypsinogen‐2 qualitative test results might be interpreted with caution when used for diagnosing acute pancreatitis. [ABSTRACT FROM AUTHOR] more...
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- 2024
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18. Uterine cervical conisation and chorioamnionitis: A nationwide observational study.
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Wada, Yoshimitsu, Takahashi, Hironori, Ogoyama, Manabu, Horie, Kenji, Suzuki, Hirotada, Usui, Rie, Jwa, Seung Chik, Ohkuchi, Akihide, and Fujiwara, Hiroyuki
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CONIZATION ,CHORIOAMNIONITIS ,PREMATURE rupture of fetal membranes ,PREMATURE labor - Abstract
Objective: To investigate whether conisation increases chorioamnionitis (CAM) and assess whether this risk differs between preterm and term periods. Furthermore, we estimated mediation effects of CAM between conisation and preterm birth (PTB). Design: A nationwide observational study. Setting: Japan. Population: Singleton pregnant women derived from the perinatal registry database of the Japan Society of Obstetrics and Gynaecology between 2013 and 2019. Methods: The association between a history of conisation and clinical CAM was examined using a multivariable logistic regression model with multiple imputation. We conducted mediation analysis to estimate effects of CAM on PTB following conisation. Main Outcome Measures: Clinical CAM. Results: Of 1 500 206 singleton pregnant women, 6961 (0.46%) underwent conisation and 1 493 245 (99.5%) did not. Clinical CAM occurred in 150 (2.2%) and 11 484 (0.8%) women with and without conisation, respectively. Conisation was associated with clinical CAM (odds ratio [OR] 3.09; 95% confidence interval (CI) 2.63–3.64; p < 0.001) (risk difference 1.57%; 95% CI 1.20–1.94). The association was detected among 171 440 women with PTB (OR 3.09; 95% CI 2.57–3.71), whereas it was not significant among 1 328 284 with term birth (OR 0.88; 95% CI 0.58–1.34). OR of total effect of conisation on PTB was 2.71, OR of natural indirect effect (effect explained by clinical CAM) was 1.04, and OR of natural direct effect (effect unexplained by clinical CAM) was 2.61. The proportion mediated was 5.9%. Conclusions: Conisation increased CAM occurrence. Obstetricians should be careful regarding CAM in women with conisation, especially in preterm period. Bacterial infections may be an important cause of PTB after conisation. [ABSTRACT FROM AUTHOR] more...
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- 2024
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19. Double Winding Vine‐Shaped Biphenyl with Molecular Asymmetry. Synthesis, Structure, and Properties.
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Mori, Atsunori, Maruka, Aruto, Tabuchi, Kohei, Okano, Kentaro, and Horie, Masaki
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ASYMMETRY (Chemistry) ,DIPHENYL ,MOLECULAR shapes ,METATHESIS reactions ,ETHYLENEDIAMINE - Abstract
A biphenyl derivative in which two benzene rings are strapped with two chains is prepared. The synthesized product shows molecular asymmetry, which was confirmed by HPLC analysis with chiral column and named as winding vine‐shaped biphenyl. The synthesis of such vine shaped molecule was performed by ring‐closing metathesis or alternatively by annulation with nosylated ethylenediamine. The structure of the obtained product was confirmed by X‐ray crystallographic analysis. The absolute configuration of the molecular asymmetry was assigned after leading to the corresponding camphor sulfonamide through denosylation and re‐amidation process. [ABSTRACT FROM AUTHOR] more...
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- 2024
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20. Glucagon secretion and its association with glycaemic control and ketogenesis during sodium‐glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open‐label, prospective study.
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Nakamura, Yuta, Horie, Ichiro, Kitamura, Tadahiro, Kusunoki, Yoshiki, Nishida, Kenro, Yamamoto, Akane, Hirota, Yushi, Fukui, Tomoyasu, Maeda, Yasutaka, Minami, Masae, Matsui, Takanori, Kawakami, Atsushi, and Abiru, Norio more...
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TYPE 1 diabetes , *WEIGHT loss , *BUTYRATES , *GLYCEMIC control , *SODIUM-glucose cotransporter 2 inhibitors , *CONTINUOUS glucose monitoring - Abstract
Aim: Clinical trials showed the efficacy of sodium‐glucose cotransporter 2 inhibitors for type 1 diabetes (T1D) by significant reductions in body weight and glycaemic variability, but elevated susceptibility to ketoacidosis via elevated glucagon secretion was a potential concern. The Suglat‐AID evaluated glucagon responses and its associations with glycaemic control and ketogenesis before and after T1D treatment with the sodium‐glucose cotransporter 2 inhibitor, ipragliflozin. Methods: Adults with T1D (n = 25) took 50‐mg open‐labelled ipragliflozin daily as adjunctive to insulin. Laboratory/clinical data including continuous glucose monitoring were collected until 12 weeks after the ipragliflozin initiation. The participants underwent a mixed‐meal tolerance test (MMTT) twice [before (first MMTT) and 12 weeks after ipragliflozin treatment (second MMTT)] to evaluate responses of glucose, C‐peptide, glucagon and β‐hydroxybutyrate. Results: The area under the curve from fasting (0 min) to 120 min (AUC0‐120min) of glucagon in second MMTT were significantly increased by 14% versus first MMTT. The fasting and postprandial β‐hydroxybutyrate levels were significantly elevated in second MMTT versus first MMTT. The positive correlation between postprandial glucagon secretion and glucose excursions observed in first MMTT disappeared in second MMTT, but a negative correlation between fasting glucagon and time below range (glucose, <3.9 mmol/L) appeared in second MMTT. The percentage changes in glucagon levels (fasting and AUC0‐120min) from baseline to 12 weeks were significantly correlated with those in β‐hydroxybutyrate levels. Conclusions: Ipragliflozin treatment for T1D increased postprandial glucagon secretion, which did not exacerbate postprandial hyperglycaemia but might protect against hypoglycaemia, leading to reduced glycaemic variability. The increased glucagon secretion might accelerate ketogenesis when adequate insulin is not supplied. [ABSTRACT FROM AUTHOR] more...
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- 2024
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21. Investigation of Calibration Methodology Using Mouth Airflow for Wearable Sensor Toward Quantitative Respiration Monitoring.
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Horie, Kenta, Al Farisi, Muhammad Salman, Hasegawa, Yoshihiro, Matsushima, Miyoko, Kawabe, Tsutomu, and Shikida, Mitsuhiro
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WEARABLE technology , *RESPIRATION , *CALIBRATION , *AIR flow , *VENTILATION , *MOTION , *LABORATORY animals , *VITAL signs - Abstract
Present wearable sensors are able to measure the frequency of vital signs such as respiration rate and heartbeat rate, but unable to measure those quantitatively, e.g. respiratory volume and heartbeat strength. Meanwhile, airflow at mouth contains both the respiration and the heartbeat quantitative signals. In this study, we propose a calibration method for a wearable vital sensor attached on the chest using the airflow at the mouth for quantitative respiration monitoring. An artificial ventilator and an experimental animal were introduced as test benches prior to human clinical experiment. As a proof of concept, a micro‐electro mechanical systems (MEMS) airflow sensor and a wearable accelerometer were implemented to both the test benches. The velocity output of the piston motion measured by the wearable sensor conformed with the airflow rate output, and the obtained results indicated that the wearable sensor can monitor not only the frequency of vital signs but also quantitative magnitudes such as the respiratory volume. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR] more...
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- 2024
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22. Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch‐repair deficiency.
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Makino, Kenta, Ishii, Takamichi, Takeda, Haruhiko, Saito, Yoichi, Fujiwara, Yukio, Fujimoto, Masakazu, Ito, Takashi, Wakama, Satoshi, Kumagai, Ken, Munekage, Fumiaki, Horie, Hiroshi, Tomofuji, Katsuhiro, Oshima, Yu, Uebayashi, Elena Yukie, Kawai, Takayuki, Ogiso, Satoshi, Fukumitsu, Ken, Takai, Atsushi, Seno, Hiroshi, and Hatano, Etsuro more...
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DNA mismatch repair ,LIVER cancer ,HEPATOCELLULAR carcinoma ,CLINICAL pathology ,STEM cells ,CLUSTER analysis (Statistics) - Abstract
Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole‐exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch‐repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR] more...
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- 2024
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23. Identification of uromodulin deposition in the stroma of perinephric fibromyxoid nephrogenic adenoma by mass spectrometry.
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Yoshimura, Kaori, Ito, Yukinobu, Suzuki, Mina, Horie, Masafumi, Nishiuchi, Takumi, Shintani‐Domoto, Yukako, Shigehara, Kazuyoshi, Oshima, Hiroko, Oshima, Masanobu, Goto, Akiteru, Nojima, Takayuki, Tsuzuki, Toyonori, Mizokami, Atsushi, Ikeda, Hiroko, and Maeda, Daichi more...
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UROMODULIN ,MASS spectrometry ,ADENOMA ,RENAL tubular transport disorders ,URINARY organs ,RADIATION injuries - Abstract
Nephrogenic adenoma (NA) is an epithelial lesion that usually occurs in the mucosa of the urinary tract. Rare cases of deep infiltrative or perinephric lesions have also been reported. Recently, NA with characteristic fibromyxoid stroma (fibromyxoid NA) has been proposed as a distinct variant. Although shedding of distal renal tubular cells due to urinary tract rupture has been postulated as the cause of NA in general, the mechanism underlying extraurinary presentation of NA and fibromyxoid stromal change in fibromyxoid NA remains unknown. In this study, we performed mass spectrometry (MS) analysis in a case of perinephric fibromyxoid NA of an 82‐year‐old man who underwent right nephroureterectomy for distal ureteral cancer. The patient had no prior history of urinary tract injury or radiation. Periodic acid‐Schiff staining‐positive eosinophilic structureless deposits in the stroma of fibromyxoid NA were microdissected and subjected to liquid chromatography/MS. The analysis revealed the presence of a substantial amount of uromodulin (Tamm−Horsfall protein). The presence of urinary content in the stroma of perinephric fibromyxoid NA suggests that urinary tract rupture and engraftment of renal tubular epithelial cells directly cause the lesion. [ABSTRACT FROM AUTHOR] more...
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- 2024
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24. Radiomics analysis using non‐contrast computed tomography for predicting high‐dependency unit admission in patients with acute pyelonephritis.
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Horie, Toshinari, Fujiwara, Motohiro, Waseda, Yuma, Tanaka, Hajime, Yoshida, Soichiro, and Fujii, Yasuhisa
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URINARY tract infections , *MACHINE learning , *TEXTURE analysis (Image processing) , *COMPUTED tomography , *FEATURE extraction - Abstract
This article discusses the use of radiomics analysis (RA) using non-contrast computed tomography (NCCT) to predict high-dependency unit (HDU) admission in patients with acute pyelonephritis (AP). AP is a severe urinary tract infection that can lead to sepsis and may require intensive care. The study analyzed 77 AP patients who underwent NCCT and found that incorporating RA into the Quick Sequential Organ Failure Assessment (qSOFA) score improved the accuracy of diagnosing AP severity. The findings suggest that RA using NCCT can be a valuable tool in assessing the severity of AP. [Extracted from the article] more...
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- 2024
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25. Genomic evolutional analysis of surgical resected specimen to assess osimertinib as a first‐line therapy in two patients with lung cancer harboring EGFR mutation: Case series.
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Koba, Hayato, Yoneda, Taro, Morita, Hiroko, Kimura, Hideharu, Murase, Yuya, Terada, Nanao, Tambo, Yuichi, Horie, Masafumi, Kasahara, Kazuo, Matsumoto, Isao, and Yano, Seiji
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PROTEIN kinase inhibitors ,HETEROCYCLIC compounds ,BIOPSY ,POSTOPERATIVE care ,GENOMICS ,ACRYLAMIDE ,INDOLE compounds ,LUNG tumors ,AMINES ,GENETIC mutation ,CASE studies ,EPIDERMAL growth factor receptors ,DISEASE progression - Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is crucial for patients with lung cancer harboring EGFR mutations. However, almost all patients experience disease progression, regardless of their response to the targeted therapy, necessitating the development of additional treatment options. Two patients with lung cancer harboring EGFR‐L858R mutations in exon 21 were treated by surgical resection during successful osimertinib treatment. Because the pathological diagnosis was suspected to be pleural metastasis, osimertinib treatment was continued until disease progression. We analyzed the evolution of genomic alterations and the levels of AXL using tumor specimens obtained by repeated biopsies during the course of treatment: initial diagnosis, operation, and disease progression. Genetic alterations detected at the three time points were dramatically changed and showed reductions in numbers, while EGFR‐L858R mutations were detected in all samples tested in both patients. Immunohistochemical expression of AXL remained positive from the beginning of analysis to disease progression. Clonal evolution under oncogenesis is related to gradual accumulation of genomic alterations during tumor growth. However, our case series revealed that volume reduction procedures may cause this phenomenon. Therefore, identification of intrinsic drug‐resistant cells in tumors may be as important as detection of acquired genetic alterations. [ABSTRACT FROM AUTHOR] more...
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- 2024
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26. Design of a hybrid left ventricular assist device with a new wireless charging system.
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Horie, Hideyuki, Isoyama, Takashi, and Ishiyama, Kazushi
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WIRELESS power transmission , *HEART assist devices , *MAGNETIC torque , *ELECTRIC motors , *ELECTRIC batteries , *ENERGY transfer - Abstract
Background: The objective of this study was to design a new wireless left ventricular assist device (LVAD) that can be charged without using a conventional transcutaneous energy transfer system (TETS). Methods: Our new wireless LVAD was a hybrid pump operating in two different modes: magnetic and electric modes. The pump was driven wirelessly by extracorporeal rotating magnets in magnetic mode, whereas it was driven by electricity provided by an intracorporeal battery in electric mode. A magnetic torque transmission system was introduced to wirelessly transmit torque to the pump impeller. The intracorporeal battery was charged in magnetic mode making use of electromagnetic coils as a generator, whereas the coils were used as a motor in electric mode. To demonstrate the feasibility of our system, we conducted a bench‐top durability test for 1 week. Results: Our hybrid pump had shown sufficient pump performance as a LVAD, with a head pressure of approximately 80 mm Hg and a flow volume of 5.0 L/min, for 1 week. The intracorporeal battery was wirelessly charged enough to power electric mode for 2.5 h a day throughout the 1‐week durability test. Conclusions: Our hybrid wireless LVAD system demonstrated the possibility of a wireless LVAD and has the potential to reduce medical complications of LVAD therapy. [ABSTRACT FROM AUTHOR] more...
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- 2024
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27. Do maxillary dentures protect the skull base from penetration injury?
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Hino, Shunsuke, Iijima, Yosuke, Mochizuki, Shuto, Nakayama, Nami, Yamada, Miki, Horie, Norio, and Kaneko, Takahiro
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SKULL base ,DENTURES ,MAXILLARY sinus ,FOREIGN bodies ,PENETRATING wounds ,MAXILLARY sinus diseases - Abstract
Key Clinical Message: Foreign bodies penetrating from the oral cavity can damage surrounding tissues. This case is considered an extremely rare and fortunate instance in which a maxillary denture appeared to weaken the external force and change the direction of the scissors, preventing damage to vital organs. The patient was a 73‐year‐old man. While on a ladder pruning a plant, he accidentally fell. The gardening scissors passed through the maxillary sinus from the maxillary alveolus and penetrated below the zygomatic arch. At the time of injury, the patient was wearing a metal‐frame denture on the maxilla, and contact between the cutting edge and the denture was speculated to have weakened the piercing force of the blade and changed the direction of the cutting edge. This extremely rare case demonstrates how a maxillary denture could reduce the severity of a penetrating injury caused by scissors. [ABSTRACT FROM AUTHOR] more...
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- 2024
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28. Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.
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Yamakawa, Nobuhiro, Umeda, Masahiro, Yoshii, Yumi, Mitsudo, Kenji, Noguchi, Makoto, Kusukawa, Jingo, Katakura, Akira, Nakayama, Hideki, Sasaki, Masashi, Noguchi, Tadahide, Ueda, Michihiro, Bukawa, Hiroki, Yagihara, Kazuhiro, Horie, Akihisa, Miyazaki, Akihiro, Chikazu, Daichi, Tomihara, Kei, Mishima, Katsuaki, Otsuru, Mitsunobu, and Asoda, Seiji more...
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DRUG efficacy ,RESEARCH ,MOUTH tumors ,SCIENTIFIC observation ,MULTIVARIATE analysis ,CANCER relapse ,METASTASIS ,RETROSPECTIVE studies ,NIVOLUMAB ,DESCRIPTIVE statistics ,PROGRESSION-free survival ,SQUAMOUS cell carcinoma ,PATIENT safety ,OVERALL survival ,EVALUATION - Abstract
Objectives: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. Materials and Methods: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression‐free and overall survival. Progression‐free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression‐free and overall survival were identified using multivariate analysis. Results: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1‐ and 2‐year progression‐free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression‐free survival were performance status and immune‐related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune‐related adverse events. Conclusion: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients. [ABSTRACT FROM AUTHOR] more...
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- 2024
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29. Terminus‐Selective Covalent Immobilization of Heparin on a Thermoresponsive Surface Using Click Chemistry for Efficient Binding of Basic Fibroblast Growth Factor.
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Onodera, Yu, Kobayashi, Jun, Mitani, Seiji, Hosoda, Chihiro, Banno, Kimihiko, Horie, Kyoji, Okano, Teruo, Shimizu, Tatsuya, Shima, Midori, and Tatsumi, Kohei
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- 2024
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30. Tumour tissue‐derived small extracellular vesicles reflect molecular subtypes of bladder cancer.
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Dong, Liang, Feng, Mingxiao, Kuczler, Morgan D., Horie, Kengo, Kim, Chi‐Ju, Ma, Zehua, Lombardo, Kara, Lyons, Heather, Amend, Sarah R., Kates, Max, Bivalacqua, Trinity J., McConkey, David, Xue, Wei, Choi, Woonyoung, and Pienta, Kenneth J. more...
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EXTRACELLULAR vesicles ,BLADDER cancer ,TISSUES ,TRANSMISSION electron microscopy ,TUMORS ,RNA sequencing - Abstract
mRNA‐based molecular subtypes have implications for bladder cancer prognosis and clinical benefit from certain therapies. Whether small extracellular vesicles (sEVs) can reflect bladder cancer molecular subtypes is unknown. We performed whole transcriptome RNA sequencing for formalin fixed paraffin embedded (FFPE) tumour tissues and sEVs separated from matched tissue explants, urine and plasma in patients with bladder cancer. sEVs were separated using size‐exclusion chromatography, and characterized by transmission electron microscopy, nano flow cytometry and western blots, respectively. High yield of sEVs were obtained using approximately 1 g of tissue, incubated with media for 30 min. FFPE tumour tissue and tumour tissue‐derived sEVs demonstrated good concordance in molecular subtype classification. All urinary sEVs were classified as luminal subtype, while all plasma sEVs were classified as Ba/Sq subtype, regardless of the molecular subtypes indicated by their matched FFPE tumour tissue. The comparison within urine sEVs, which may exclude the sample type specific background, could pick up the different biology between NMIBC and MIBC, as well as the signature genes related to molecular subtypes. Four candidate sEV‐related bladder cancer‐specific mRNA biomarkers, FAM71E2, OR4K5, FAM138F and KRTAP26‐1, were identified by analysing matched urine sEVs, tumour tissue derived sEVs, and adjacent normal tissue derived sEVs. Compared to sEVs separated from biofluids, tissue‐derived sEVs may reflect more tissue‐ or disease‐specific biological features. Urine sEVs are promising biomarkers to be used for liquid biopsy‐based molecular subtype classification, but the current algorithm needs to be modified/adjusted. Future work is needed to validate the four new bladder cancer‐specific biomarkers in large cohorts. [ABSTRACT FROM AUTHOR] more...
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- 2024
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31. Exosomes secreted by ST3GAL5high cancer cells promote peritoneal dissemination by establishing a premetastatic microenvironment.
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Horie, Misato, Takagane, Kurara, Itoh, Go, Kuriyama, Sei, Yanagihara, Kazuyoshi, Yashiro, Masakazu, Umakoshi, Michinobu, Goto, Akiteru, Arita, Junichi, and Tanaka, Masamitsu
- Abstract
Peritoneal dissemination of cancer affects patient survival. The behavior of peritoneal mesothelial cells (PMCs) and immune cells influences the establishment of a microenvironment that promotes cancer cell metastasis in the peritoneum. Here, we investigated the roles of lactosylceramide alpha‐2,3‐sialyltransferase (ST3G5; also known as ST3GAL5 and GM3 synthase) in the exosome‐mediated premetastatic niche in peritoneal milky spots (MSs). Exosomes secreted from ST3G5high cancer cells (ST3G5high‐cExos) were found to contain high levels of hypoxia‐inducible factor 1‐alpha (HIF1α) and accumulated in MSs via uptake in macrophages (MΦs) owing to increased expression of sialic acid‐binding Ig‐like lectin 1 (CD169; also known as SIGLEC1). ST3G5high‐cExos induced pro‐inflammatory cytokines and glucose metabolic changes in MΦs, and the interaction of these MΦs with PMCs promoted mesothelial–mesenchymal transition (MMT) in PMCs, thereby generating αSMA+ myofibroblasts. ST3G5high‐cExos also increased the expression of immune checkpoint molecules and T‐cell exhaustion in MSs, which accelerated metastasis to the omentum. These events were prevented following ST3G5 depletion in cancer cells. Mechanistically, ST3G5high‐cExos upregulated chemokines, including CC‐chemokine ligand 5 (CCL5), in recipient MΦs and dendritic cells (DCs), which induced MMT and immunosuppression via activation of signal transducer and activator of transcription 3 (STAT3). Maraviroc, a C‐C chemokine receptor type 5 (CCR5) antagonist, prevented ST3G5high‐cExo‐mediated MMT, T‐cell suppression, and metastasis in MSs. Our results suggest ST3G5 as a suitable therapeutic target for preventing cExo‐mediated peritoneal dissemination. [ABSTRACT FROM AUTHOR] more...
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- 2024
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32. Eribulin for patients with metastatic extramammary Paget disease: Study protocol for a single‐arm phase II trial.
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Maeda, Takuya, Yanagi, Teruki, Tokuchi, Keiko, Funakoshi, Takeru, Horie, Nao, Isoe, Toshiyuki, Ito, Yoichi M., Sato, Norihiro, and Ujiie, Hideyuki
- Subjects
ERIBULIN ,RESEARCH protocols ,PROGRESSION-free survival ,OVERALL survival ,METASTASIS - Abstract
Extramammary Paget disease (EMPD) is a rare cutaneous malignancy that predominantly affects the anogenital areas of the elderly. Although the efficacy of docetaxel and other cytotoxic agents for advanced EMPD has been reported in small retrospective case studies, no treatment has been proven effective in prospective clinical trials. We established the world's first in vivo EMPD experimental model (a patient‐derived xenograft model). In our treatment experiment, xenograft tumours showed a remarkable response to eribulin. This study evaluates the efficacy of eribulin for patients with advanced EMPD. In October 2022, we started a single‐arm phase II trial to evaluate the efficacy of eribulin as a treatment for adult patients with unresectable EMPD with measurable lesions. Enrolment in this clinical trial is open to patients with any prior treatment for EMPD. The primary endpoint is overall response rate; the secondary endpoints include disease control rate, overall survival, progression‐free survival and adverse events. The study protocol was approved by the Ethics Committee of Hokkaido University and the other collaborating institutions. If the primary endpoint is met, it is our hope that eribulin will be regarded as a standard medication for patients with advanced EMPD. [ABSTRACT FROM AUTHOR] more...
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- 2024
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33. Comprehensive analyses of the clinicopathological features and genomic mutations of combined hepatocellular‐cholangiocarcinoma.
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Ito, Takashi, Ishii, Takamichi, Takeda, Haruhiko, Sumiyoshi, Shinji, Tomofuji, Katsuhiro, Wakama, Satoshi, Makino, Kenta, Horie, Hiroshi, Kumagai, Ken, Takai, Atsushi, Uebayashi, Elena Yukie, Ogiso, Satoshi, Fukumitsu, Ken, Haga, Hironori, Seno, Hiroshi, and Hatano, Etsuro more...
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GENETIC mutation ,CLINICAL pathology ,LIVER cancer ,SEQUENCE analysis ,EPIGENETICS - Abstract
Aim: Combined hepatocellular‐cholangiocarcinoma (cHCC‐CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC‐CCA remains to be elucidated. Methods: Whole‐exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC‐CCAs. The whole‐exome analyses and clinicopathological information were integrated. Results: TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC‐CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC‐CCA tumors. Recurrent and co‐occurrent HCC tumors in the same patients with cHCC‐CCA had either common or different mutation patterns from the primary cHCC‐CCA tumors in each case. Conclusions: The study suggested that there were two subtypes of cHCC‐CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC‐CCA was derived from an identical clone. [ABSTRACT FROM AUTHOR] more...
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- 2024
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34. Low anterior resection syndrome: Incidence and association with quality of life.
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Homma, Yuko, Mimura, Toshiki, Koinuma, Koji, Horie, Hisanaga, Lefor, Alan Kawarai, and Sata, Naohiro
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RECTUM tumors ,QUALITY of life ,JAPANESE people ,FECAL incontinence ,RECTAL surgery - Abstract
Aim: Low anterior resection syndrome (LARS) causes devastating symptoms and impairs quality of life (QOL). Although its incidence and risk factors have been reported, these data are scarce in Japan. This study aimed to elucidate the incidence and risk factors of LARS as well as to evaluate its association with QOL in Japanese patients. Method: Patients with anal defecation at the time of the survey between November 2020 and April 2021 were included, among those who underwent anus‐preserving surgery for rectal tumors between 2014 and 2019 in tertiary referral university hospital. The severity of LARS and QOL were evaluated with the LARS score and the Japanese version of the fecal incontinence quality of life scale (JFIQL), respectively. Primary endpoint was the incidence of major LARS. Secondary endpoints were risk factors and association with JFIQL. Results: Of 332 eligible patients, 238 (71.7%) answered the LARS survey completely. The incidence of major LARS was 22% overall, and 48% when limited to lower tumors. Independent risk factors included lower tumors (OR: 7.0, 95% CI: 2.1–23.1, p = 0.001) and surgical procedures with lower anastomoses (OR: 4.6, 95% CI: 1.2–18.5, p = 0.03). The JFIQL generic score correlated moderately with the LARS score (correlation coefficient of −0.65). The JFIQL generic score was also significantly lower in lower tumors. Conclusions: The incidence of major LARS is 22% in Japanese patients, and independent risk factors include lower tumors and surgical procedures with lower anastomoses. More severe LARS is associated with worse QOL which is significantly more impaired in patients with lower tumors. [ABSTRACT FROM AUTHOR] more...
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- 2024
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35. Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer's.
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Salvadó, Gemma, Horie, Kanta, Barthélemy, Nicolas R., Vogel, Jacob W, Binette, Alexa Pichet, Chen, Charles D., Gordon, Brian A., Benzinger, Tammie L.S., Holtzman, David M., Morris, John C, Palmqvist, Sebastian, Stomrud, Erik, Janelidze, Shorena, Ossenkoppele, Rik, Schindler, Suzanne E., Bateman, Randall J., and Hansson, Oskar more...
- Abstract
Background: Staging Alzheimer's disease (AD) allows for the identification of key milestones and inflection points in the disease course. However, most current in vivo disease staging methods rely on costly and low‐accessible measures such as PET. Our objective was to generate and evaluate a staging model based on multiple cerebrospinal fluid (CSF) biomarkers. Method: We created a staging model using the Subtype and Stage Inference (SuStaIn) algorithm in 426 participants covering the whole AD spectrum (Table 1) by evaluating CSF Ab42/40 and 5 CSF tau markers: the proportion of tau phosphorylated at three threonine residues (pT205/T205, pT217/T217, and pT231/T231), and the concentrations of microtubule‐binding region of tau at residue 243 [MTBR‐tau243] and total‐tau [mid‐domain containing T212‐221]). We investigated associations between CSF stages and cross‐sectional and longitudinal changes in amyloid and tau pathologies, neurodegeneration and cognition using linear regression models. ROC curves were used to identify the optimal stage for predicting positivity in imaging biomarkers and to separate AD vs non‐AD cognitive symptoms. We also tested the relative risk of progression from cognitively unimpaired or MCI to AD‐type dementia using Kaplan‐Meier curves and Cox‐proportional Hazard models. Creation of the model and cross‐sectional analyses were replicated in an independent cohort (n = 222, Table 1). Result: SuStaIn revealed that only one subtype was present and that five CSF biomarkers (ordered: Ab42/40, pT217/T217, pT205/T205, MTBR‐tau243, T212‐221) were sufficient to create an accurate disease staging model (Fig.1A‐B). Increasing stages (0‐5) were associated with increased abnormality in other AD‐related biomarkers (Fig.1C). In both cohorts, stage ≥2 accurately predicted amyloid‐PET positivity (AUC≥0.89), stage ≥4 predicted tau‐PET (AUC≥0.94) and neurodegeneration positivity (AUC≥0.81). In the main cohort, stage≥2 separated non‐AD from AD‐related cognitive impairment (AUC = 0.96). Longitudinal changes for several AD‐biomarkers by stages are presented in (Fig.2A). Higher stages (4‐5) at baseline were associated with higher hazard ratios (HR) of progressing to AD‐type dementia (CU&MCI: HR = 4.6[2.0,10.9], MCI: HR = 3.5[1.5,8.1], Fig.2B‐C). Conclusion: Our results suggest that the AD continuum can be accurately staged with a single CSF sample, which may be useful in the clinical setting for patient management but also as a tool in clinical trials for selection and monitoring of study participants. [ABSTRACT FROM AUTHOR] more...
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- 2023
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36. T‐cell receptor repertoire analysis of CD4‐positive T cells from blood and an affected organ in an autoimmune mouse model.
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Ishikawa, Tatsuya, Horie, Kenta, Takakura, Yuki, Ohki, Houko, Maruyama, Yuya, Hayama, Mio, Miyauchi, Maki, Miyao, Takahisa, Hagiwara, Naho, Kobayashi, Tetsuya J., Akiyama, Nobuko, and Akiyama, Taishin more...
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T cells , *BLOOD cells , *LABORATORY mice , *T cell receptors , *ANIMAL disease models , *SYMPTOMS - Abstract
One hallmark of some autoimmune diseases is the variability of symptoms among individuals. Organs affected by the disease differ between patients, posing a challenge in diagnosing the affected organs. Although numerous studies have investigated the correlation between T cell antigen receptor (TCR) repertoires and the development of infectious and immune diseases, the correlation between TCR repertoires and variations in disease symptoms among individuals remains unclear. This study aimed to investigate the correlation of TCRα and β repertoires in blood T cells with the extent of autoimmune signs that varies among individuals. We sequenced TCRα and β of CD4+CD44highCD62Llow T cells in the blood and stomachs of mice deficient in autoimmune regulator (Aire) (AIRE KO), a mouse model of human autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy. Data analysis revealed that the degree of similarity in TCR sequences between the blood and stomach varied among individual AIRE KO mice and reflected the extent of T cell infiltration in the stomach. We identified a set of TCR sequences whose frequencies in blood might correlate with extent of the stomach manifestations. Our results propose a potential of using TCR repertoires not only for diagnosing disease development but also for diagnosing affected organs in autoimmune diseases. [ABSTRACT FROM AUTHOR] more...
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- 2023
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37. Plasma levels and urinary excretion of protein Z in patients with urolithiasis.
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Kaneko, Kiyoko, Yasuda, Makoto, Fukuuchi, Tomoko, Yamaoka, Noriko, Takahashi, Kei, Mawatari, Ken‐ichi, Isotani, Shuji, Horie, Shigeo, and Nakagawa, Tohru
- Subjects
URINARY calculi ,EXCRETION ,EXTRACELLULAR matrix proteins ,CALCIUM oxalate ,BLOOD coagulation ,CREATININE - Abstract
Objectives: Protein Z (PZ) is a γ‐carboxyglutamic acid protein present in plasma that is involved in blood coagulation. Detailed analysis of urinary stones from patients with urolithiasis has revealed that PZ is often found in urinary stones composed of calcium oxalate monohydrate. In this study, we compared blood and urinary PZ concentrations between healthy individuals and patients with urolithiasis. Methods: Plasma and urine were collected from healthy individuals and patients with urolithiasis who provided informed consent. PZ was detected as a urinary stone matrix protein in some of the patients. PZ was quantified by ELISA, creatinine was measured by the enzymatic method, and the total protein concentration was measured by the Bradford method. Results: The plasma PZ level was 2.54 ± 1.02 μg/mL in healthy individuals and that in urolithiasis patients classified by stone history were from 1.16 ± 0.77 to 3.73 ± 1.09 μg/mL, which was not significantly different. The urinary excretion of PZ (PZ/creatinine) was also not different in patients with urolithiasis and in healthy individuals (from 54.1 ± 40.9 to 95.4 ± 69.4 ng/mg vs. 73.3 ± 36.0 ng/mg). A positive correlation was found between the plasma PZ level and creatinine‐corrected urinary PZ concentration (r = 0.46). Conclusions: Both the plasma level and urinary excretion of PZ in urolithiasis patients were not significantly different with normal individuals. PZ detected in urinary stones as a matrix protein is thought to be incorporated into urinary stones regardless of blood and urine levels of PZ. [ABSTRACT FROM AUTHOR] more...
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- 2023
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38. Impact of Preoperative Stoma Site Marking on Morbidity and Mortality in Patients with Colorectal Perforation: A Nationwide Retrospective Cohort Study.
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Watanabe, Jun, Sasabuchi, Yusuke, Ohbe, Hiroyuki, Nakajima, Mikio, Matsui, Hiroki, Miki, Atsushi, Horie, Hisanaga, Kotani, Kazuhiko, Yasunaga, Hideo, and Sata, Naohiro
- Subjects
SURGICAL emergencies ,SURGICAL stomas ,PROPENSITY score matching ,COHORT analysis ,ELECTIVE surgery ,PROCTOLOGY ,MORTALITY - Abstract
Background: Preoperative stoma site marking reduces the incidence of complications from elective surgery. However, the impact of stoma site marking in emergency patients with colorectal perforation remains unclear. This study aimed to assess the impact of stoma site marking on morbidity and mortality in patients with colorectal perforation who underwent emergency surgery. Methods: This retrospective cohort study used the Japanese Diagnosis Procedure Combination inpatient database from April 1, 2012, to March 31, 2020. We identified patients who underwent emergency surgery for colorectal perforation. We compared outcomes between those with and without stoma site marking using propensity score matching to adjust for confounding factors. The primary outcome was the overall complication rate, and the secondary outcomes were stoma-related, surgical, and medical complications and 30-day mortality. Results: We identified 21,153 patients (682 with stoma site marking and 20,471 without stoma site marking) and grouped them into 682 pairs using propensity score matching. The overall complication rates were 23.5% and 21.4% in the groups with and without stoma site marking, respectively (p = 0.40). Stoma site marking was not associated with a decrease in stoma-related, surgical, or medical complications. The 30-day mortality did not differ significantly between the groups with and without stoma site marking (7.9% vs. 8.4%, p = 0.843). Conclusions: Preoperative stoma site marking was not associated with a reduction in morbidity and mortality in patients with colorectal perforation who underwent emergency surgery. [ABSTRACT FROM AUTHOR] more...
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- 2023
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39. Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study.
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Onuki, Mamiko, Takahashi, Fumiaki, Iwata, Takashi, Nakazawa, Hiroshi, Yahata, Hideaki, Kanao, Hiroyuki, Horie, Koji, Konnai, Katsuyuki, Nio, Ai, Takehara, Kazuhiro, Kamiura, Shoji, Tsuda, Naotake, Takei, Yuji, Shigeta, Shogo, Matsumura, Noriomi, Yoshida, Hiroyuki, Motohara, Takeshi, Yamazaki, Hiroyuki, Nakamura, Keiichiro, and Hamanishi, Junzo more...
- Abstract
The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high‐grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population‐based cancer registry, the incidence of ICC among young women aged 20–29 years showed a significant decline from 3.6 to 2.8 per 100 000 women‐years during 2016–2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20–29 years also decreased from 256 cases to 135 cases during 2011–2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20–29 years during 2017–2022 (90.5%–64.7%, p = 0.05; Cochran–Armitage trend test). This is the first report to suggest population‐level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination. [ABSTRACT FROM AUTHOR] more...
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- 2023
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40. Prognostic Impact of Renal Function on 5-Year Outcomes After Fractional Flow Reserve-Guided Deferral of Revascularization.
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Ryosuke Itakura, Shoichi Kuramitsu, Jun Kikuchi, Yoshiaki Kawase, Takuya Mizukami, Tomohiro Shinozaki, Kazunori Horie, Hiroaki Takashima, Hidenobu Terai, Yuetsu Kikuta, Takayuki Ishihara, Tatsuya Saigusa, Tomohiro Sakamoto, Nobuhiro Suematsu, Yasutsugu Shiono, Taku Asano, Kenichi Tsujita, Katsuhiko Masamura, Tatsuki Doijiri, and Fumitoshi Toyota more...
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- 2023
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41. Change in cerebrospinal fluid tau microtubule binding region detects symptom onset, cognitive decline, tangles, and atrophy in Dominantly Inherited Alzheimer's Disease
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Horie, Kanta, Li, Yan, Allegri, Ricardo, Mendez, Patricio Chrem, Ikeuchi, Takeshi, Kasuga, Kensaku, Noble, James, Farlow, Martin, Chhatwal, Jasmeer, Day, Gregory S, Schofield, Peter R, Masters, Colin L, Barthélemy, Nicolas R, Levin, Johannes, Jucker, Mathias, Lee, Jae-Hong, Roh, Jee Hoon, Sato, Chihiro, Sachdev, Pallavi, Koyama, Akihiko, Reyderman, Larisa, Bateman, Randall J, McDade, Eric, Gordon, Brian A, Network, Dominantly Inherited Alzheimer, Hassenstab, Jason, Benzinger, Tammie L S, Fagan, Anne M, Morris, John C, Karch, Celeste M, and Xiong, Chengjie more...
- Subjects
Neurology ,Neurology (clinical) ,ddc:610 - Abstract
Identifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR-tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer disease related neurofibrillary tau pathological changes. We examined CSF MTBR-tau species in dominantly inherited Alzheimer disease (DIAD) mutation carriers to assess the association with AD biomarkers and clinical symptoms.Cross-sectional and longitudinal CSF from 229 DIAD mutation and 130 mutation non-carriers had sequential characterization of N-terminal/mid-domain phosphorylated tau (p-tau) followed by MTBR-tau species and tau-PET, other soluble tau and amyloid biomarkers, comprehensive clinical and cognitive assessments, and brain magnetic resonance imaging of atrophy.CSF MTBR-tau species located within the putative 'border' region and one species corresponding to the 'core' region of aggregates in neurofibrillary tangles increased during the presymptomatic stage and decreased during the symptomatic stage. The 'border' MTBR-tau species were associated with amyloid pathology and CSF p-tau; while the 'core' MTBR-tau species were associated stronger with tau-PET and CSF measures of neurodegeneration. The ratio of the border to the core species provided a continuous measure of increasing amounts that tracked clinical progression and NFT.Changes in CSF soluble MTBR-tau species preceded the onset of dementia, tau tangle increase, and atrophy in DIAD. The ratio of 4R-specific MTBR-tau (border) to the NFT (core) MTBR-tau species corresponds to the pathology of NFT in DIAD and change with disease progression. The dynamics between different MTBR-tau species in the CSF may serve as a marker of tau-related disease progression and target engagement of anti-tau therapeutics. This article is protected by copyright. All rights reserved. more...
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- 2023
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42. Endovascular coils mimicking accidental ingestion of a dental‐related foreign body in radiographic imaging.
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Nakayama, Nami, Nakamura, Satoshi, Yamada, Miki, Iijima, Yosuke, Hino, Shunsuke, Horie, Norio, and Kaneko, Takahiro
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FOREIGN bodies ,BODY image ,DENTURES ,CHEST X rays ,INGESTION ,ORAL surgeons - Abstract
Key Clinical Message: If a foreign body is seen on chest or abdominal radiographs, accidental aspiration or ingestion of a dental‐related foreign body may be suspected. This report describes a case in which vascular embolization coils seen on radiography were suspected to represent a swallowed dental prosthesis. A 72‐year‐old man with a history of endovascular embolization of portosystemic shunt was admitted for mandibular fracture. On hospital day 2, a foreign body was noted on chest radiographs taken to confirm pleural effusion. No foreign body had been evident on radiographs of the same area the previous day. The foreign body was suspected to be a dental prosthesis, but intraoral examination ruled out this possibility, and the foreign body turned out to be metal coils used to embolize the shunt. Dentists and oral surgeons should be aware that medical devices such as vascular embolization coils can produce images similar to a dental‐related foreign body on chest or abdominal radiographs, and dental‐related foreign body ingestion or aspiration should be considered in the differential diagnosis. [ABSTRACT FROM AUTHOR] more...
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- 2023
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43. Successful wound closure using fibrin glue for intractable neobladder‐urethral anastomosis leakage after radical cystectomy and neobladder reconstruction.
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Ishikawa, Keisuke, Nagata, Masayoshi, Anno, Yuta, Yamagishi, Miki, China, Toshiyuki, Shimizu, Fumitaka, Isotani, Shuji, Muto, Satoru, and Horie, Shigeo
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- 2023
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44. High‐grade vaginal intraepithelial neoplasia after hysterectomy for high‐grade cervical intraepithelial neoplasia: Is hysterectomy a "definitive" treatment compared to conization?
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Tanaka, Miyu, Yamanoi, Koji, Taki, Mana, Kitamura, Sachiko, Sunada, Masumi, Chigusa, Yoshitsugu, Horie, Akihito, Yamaguchi, Ken, Hamanishi, Junzo, and Mandai, Masaki
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STATISTICS ,HYSTERECTOMY ,SCIENTIFIC observation ,CONFIDENCE intervals ,ONE-way analysis of variance ,CERVICAL intraepithelial neoplasia ,RETROSPECTIVE studies ,FISHER exact test ,MANN Whitney U Test ,VAGINAL tumors ,DISEASE relapse ,T-test (Statistics) ,DESCRIPTIVE statistics ,CHI-squared test ,DATA analysis software ,DATA analysis ,ODDS ratio ,TUMOR grading ,LONGITUDINAL method - Abstract
Aim: We investigated the frequency of early recurrence of vaginal intraepithelial neoplasia grade 2/3 (VaIN 2/3) (within 2 years) after hysterectomy for cervical intraepithelial neoplasia grade 3 (CIN3). The characteristics of the clinicopathological factors common to them were explored including different surgical methods. Methods: As a retrospective observational study, a total of 647 CIN3 patients were divided into a conization and hysterectomy group (C group, n = 492; H group, n = 155), and HSIL (CIN2/3 or VaIN2/3) recurrence within 2 years after surgery was evaluated. A stratified analyses was performed. Surgical methods were divided into trans‐abdominal, trans‐vaginal, and laparoscopic. Results: The recurrence of VaIN3 was detected in four cases (2.6%) in the H group, which was similar to that of CIN2/3 in the C group, 12 out of 491 patients (2.4%). The patients who developed VaIN3 were significantly older than those who did not (median, VaIN3: 71.0; VaIN1 and less: 48.0; p < 0.0001). All VaIN3 cases were detected within 5 months, although majority of cases were negative in the margin (3/4 cases; margin negative). The method of hysterectomy was not related to the VaIN3 recurrence. Conclusion: For CIN3 patients for whom hysterectomy is the main treatment, VaIN3 can develop in 2.6% within very shortly after operation even if surgical margin was negative. The elder the age, the higher the risk of early recurrence could be. Laparoscopic surgery is considered to be acceptable methods of hysterectomy. [ABSTRACT FROM AUTHOR] more...
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- 2023
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45. Novel strategy of liver cancer treatment with modified antisense oligonucleotides targeting human vasohibin‐2.
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Horie, Sachiko, Suzuki, Yasuhiro, Yamamoto, Tsuyoshi, Obika, Satoshi, Mohri, Kohta, Kiyota, Chizuru, Ren, Qin, Warashina, Shota, Wada, Yasuhiro, Watanabe, Yasuyoshi, Mukai, Hidefumi, and Sato, Yasufumi more...
- Abstract
Vasohihibin‐2 (VASH2) is a homolog of vasohibin‐1 (VASH1) and is overexpressed in various cancers. Vasohihibin‐2 acts on both cancer cells and cancer microenvironmental cells. Previous analyses have shown that VASH2 promotes cancer progression and abrogation of VASH2 results in significant anticancer effects. We therefore propose VASH2 to be a practical molecular target for cancer treatment. Modifications of antisense oligonucleotide (ASO) such as bridged nucleic acids (BNA)‐based modification increases the specificity and stability of ASO, and are now applied to the development of a number of oligonucleotide‐based drugs. Here we designed human VASH2‐ASOs, selected an optimal one, and developed 2′,4′‐BNA‐based VASH2‐ASO. When systemically administered, naked 2′,4′‐BNA‐based VASH2‐ASO accumulated in the liver and showed its gene‐silencing activity. We then examined the effect of 2′,4′‐BNA‐based VASH2‐ASO in liver cancers. Intraperitoneal injection of naked 2′,4′‐BNA‐based VASH2‐ASO exerted a potent antitumor effect on orthotopically inoculated human hepatocellular carcinoma cells. The same manipulation also showed potent antitumor activity on the splenic inoculation of human colon cancer cells for liver metastasis. These results provide a novel strategy for the treatment of primary as well as metastatic liver cancers by using modified ASOs targeting VASH2. [ABSTRACT FROM AUTHOR] more...
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- 2023
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46. Effective magnetic hyperthermia induced by mitochondria‐targeted nanoparticles modified with triphenylphosphonium‐containing phospholipid polymers.
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Kaneko, Masahiro, Yamazaki, Hiroto, Ono, Takahiro, Horie, Masanobu, and Ito, Akira
- Abstract
Magnetic hyperthermia (MHT) is a promising cancer treatment because tumor tissue can be specifically damaged by utilizing the heat generated by nano‐heaters such as magnetite nanoparticles (MNPs) under an alternating magnetic field. MNPs are taken up by cancer cells, enabling intracellular MHT. Subcellular localization of MNPs can affect the efficiency of intracellular MHT. In this study, we attempted to improve the therapeutic efficacy of MHT by using mitochondria‐targeting MNPs. Mitochondria‐targeting MNPs were prepared by the modification of carboxyl phospholipid polymers containing triphenylphosphonium (TPP) moieties that accumulate in mitochondria. The mitochondrial localization of polymer‐modified MNPs was supported by transmission electron microscopy observations of murine colon cancer CT26 cells treated with polymer‐modified MNPs. In vitro and in vivo MHT using polymer‐modified MNPs revealed that the therapeutic effects were enhanced by introducing TPP. Our results indicate the validity of mitochondria targeting in enhancing the therapeutic outcome of MHT. These findings will pave the way for developing a new strategy for the surface design of MNPs and therapeutic strategies for MHT. [ABSTRACT FROM AUTHOR] more...
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- 2023
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47. High prevalence of frailty in patients with lower urinary tract symptoms.
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Irie, Naohiro, Muramoto, Nobuhito, Shirakawa, Tomoya, China, Toshiyuki, Kawano, Haruna, Isotani, Shuji, and Horie, Shigeo
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FRAIL elderly ,MULTIVARIATE analysis ,RETROSPECTIVE studies ,MEDICAL records ,URINARY organ diseases ,COMORBIDITY ,SYMPTOMS ,OLD age - Abstract
Aim: Older adults are more likely to be frail and have a high prevalence of urological diseases such as lower urinary tract symptoms (LUTS). The purpose of this study was to clarify the prevalence and characteristics of comorbid frailty in older patients with urological diseases. Methods: We retrospectively reviewed the medical records of 970 patient who visited the Department of Urology, Juntendo University Hospital between October 2015 and October 2016. Patients were selected who were 65 years of age or older and were being evaluated by the Kihon Checklist (KCL) to assess frailty. We examined the prevalence of comorbid frailty in urological diseases, identified factors associated with comorbid frailty in urological diseases, and examined KCL scores in urological diseases with a high prevalence of frailty. Results: A total of 405 participants were included. Of these, 21.7% were frail, 20.5% were pre‐frail, and 57.8% were robust. LUTS, overactive bladder, and neurogenic bladder showed a statistically significant relationship with comorbid frailty, with high frailty prevalence rates of 44/140 (31.4%), 19/36 (52.8%), and 4/6 (66.7%), respectively. Factors related to the comorbid frailty according to multivariate analysis were female sex (P = 0.001), older age (P < 0.001), and LUTS (P < 0.033). Of the KCL subscale scores, instrumental activities of daily living (P = 0.008), physical function (P < 0.001), oral function (P = 0.008), housebound (P = 0.009), and depression (P = 0.034) were higher in LUTS patients than in non‐LUTS patients. Conclusions: Among patients with urological diseases, those with LUTS were found to have a high prevalence of frailty. Geriatr Gerontol Int 2023; 23: 609–615. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
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48. Spheroid formation induces chemokine production in trophoblast‐derived Swan71 cells.
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Kanda, Tatsuhito, Kagami, Kyosuke, Iizuka, Takashi, Kasama, Haruki, Matsumoto, Takeo, Sakai, Yuya, Suzuki, Takuma, Yamamoto, Megumi, Matsuoka, Ayumi, Yamazaki, Rena, Hattori, Akira, Horie, Akihito, Daikoku, Takiko, Ono, Masanori, and Fujiwara, Hiroshi more...
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MACROPHAGE inflammatory proteins ,GENE expression ,CELL differentiation ,CHEMOKINES ,IMMUNE response - Abstract
Problem: In the cell column of anchoring villi, the cytotrophoblast differentiates into extravillous trophoblast (EVT) and invades the endometrium in contact with maternal immune cells. Recently, chemokines were proposed to regulate the decidual immune response. To investigate the roles of chemokines around the anchoring villi, we examined the expression profiles of chemokines in the first‐trimester trophoblast‐derived Swan71 cells using a three‐dimensional culture model. Method of Study: The gene expressions in the spheroid‐formed Swan71 cells were examined by microarray and qPCR analyses. The protein expressions were examined by immunochemical staining. The chemoattractant effects of spheroid‐formed Swan71 cells were examined by migration assay using monocyte‐derived THP‐1 cells. Results: The expressions of an EVT marker, laeverin, and matrix metalloproteases, MMP2 and MMP9, were increased in the spheroid‐cultured Swan71 cells. Microarray and qPCR analysis revealed that mRNA expressions of various chemokines, CCL2, CCL7, CCL20, CXCL1, CXCL2, CXCL5, CXCL6, CXCL8, and CXCL10, in the spheroid‐cultured Swan71 cells were up‐regulated as compared with those in the monolayer‐cultured Swan71 cells. These expressions were significantly suppressed by hypoxia. Migration assay showed that culture media derived from the spheroid‐formed Swan71 cells promoted THP‐1 cell migration. Conclusion: This study indicated that chemokine expressions in Swan71 cells increase under a spheroid‐forming culture and the culture media have chemoattractant effects. Since three‐dimensional cell assembling in the spheroid resembles the structure of the cell column, this study also suggests that chemokines play important roles in the interaction between EVT and immune cells in their early differentiation stage. [ABSTRACT FROM AUTHOR] more...
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- 2023
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49. CD30 induces Reed‐Sternberg cell‐like morphology and chromosomal instability in classic Hodgkin lymphoma cell lines.
- Author
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Watanabe, Mariko, Hatsuse, Hiromi, Nagao, Kazuaki, Nakashima, Makoto, Uchimaru, Kaoru, Otsu, Makoto, Miyazaki, Koji, and Horie, Ryouichi
- Abstract
Classic Hodgkin lymphoma (cHL) is characterized by multinucleated cells called Reed‐Sternberg (RS) cells and genetic complexity. Although CD30 also characterizes cHL cells, its biological roles are not fully understood. In this report, we examined the link between CD30 and these characteristics of cHL cells. CD30 stimulation increased multinucleated cells resembling RS cells. We found chromatin bridges, a cause of mitotic errors, among the nuclei of multinucleated cells. CD30 stimulation induced DNA double‐strand breaks (DSBs) and chromosomal imbalances. RNA sequencing showed significant changes in the gene expression by CD30 stimulation. We found that CD30 stimulation increased intracellular reactive oxygen species (ROS), which induced DSBs and multinucleated cells with chromatin bridges. The PI3K pathway was responsible for CD30‐mediated generation of multinucleated cells by ROS. These results suggest that CD30 involves generation of RS cell‐like multinucleated cells and chromosomal instability through induction of DSBs by ROS, which subsequently induces chromatin bridges and mitotic error. The results link CD30 not only to the morphological features of cHL cells, but also to the genetic complexity, both of which are characteristic of cHL cells. [ABSTRACT FROM AUTHOR] more...
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- 2023
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50. Effects of plasticizer diisobutyl adipate on the Japanese medaka (Oryzias latipes) endocrine system.
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Horie, Yoshifumi, Ramaswamy, Babu Rajendran, Ríos, Juan Manuel, Yap, Chee Kong, and Okamura, Hideo
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ENDOCRINE system ,THYROTROPIN receptors ,ORYZIAS latipes ,PLASTICIZERS ,THYROID hormone receptors ,GONADOTROPIN releasing hormone - Abstract
Plasticizer pollution of the water environment is one of the world's most serious environmental issues. Phthalate plasticizers can disrupt endocrine function in vertebrates. Therefore, this study analyzed thyroid‐related, reproduction‐related, and estrogen‐responsive genes in Japanese medaka (Oryzias latipes) to determine whether non‐phthalate diisobutyl adipate (DIBA) plasticizer could affect endocrine hormone activity or not. Developmental toxicity during fish embryogenesis was also evaluated. At a concentration of 11.57 mg/l, embryonic exposure to DIBA increased the mortality rate. Although abnormal development, including body curvature, edema, and lack of swim bladder inflation, was observed at 3.54 and 11.57 mg/l DIBA, growth inhibition and reduced swimming performance were also observed. In addition, DIBA exposure increased the levels of thyroid‐stimulating hormone beta‐subunit (tshβ) and deiodinase 1 (dio1) but decreased the levels of thyroid hormone receptor alpha (trα) and beta (trβ). These results suggest that DIBA has thyroid hormone‐disrupting activities in fish. However, kisspeptin (kiss1 and kiss2), gonadotropin‐releasing hormone (gnrh1), follicle‐stimulating hormone beta (fshβ), luteinizing hormone beta (lhβ), choriogenin H (chgH), and vitellogenin (vtg1) expression did not change dose‐dependently in response to DIBA exposure, whereas gnrh2 and vtg2 expression was elevated. These results indicate that DIBA has low estrogenic activity and does not disrupt the endocrine reproduction system in fish. Overall, this is the first report indicating that non‐phthalate DIBA plasticizer is embryotoxic and disrupt thyroid hormone activity in fish. Embryonic exposure to non‐phthalate plasticizer, DIBA resulted in abnormal embryo development, increased swim bladder non‐inflation in larvae, decreased swimming performance, and alterations in thyroid hormone‐related gene expression, indicating DIBA's potential to disrupt thyroid hormone activity in fish. However, this exposure had no dose‐dependent effect on kisspeptin, gonadotropin, chgH, and vtg1 expression, indicating DIBA's weak estrogenic activity and inability to disrupt the endocrine reproductive system in fish. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
- Full Text
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