Publications by authors named "Yosuke Fujii"

Nirmatrelvir/ritonavir (NMV/r) and molnupiravir are oral antiviral drugs approved for the treatment of early symptomatic patients with mild to moderate COVID-19 at high risk of progression to severe disease in Japan. This study evaluated, from a Japanese payer perspective, the cost-effectiveness of NMV/r compared with molnupiravir among patients with COVID-19. This cost-effectiveness model describes the COVID-19 disease history and the impact of antiviral treatment on short-term and long-term outcomes.

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  • Over 80% of hepatocellular carcinoma (HCC) cases show aberrations in the TERT gene, which plays a crucial role in cellular immortality by stabilizing telomere length, although its exact role in liver cancer development is not fully understood.
  • Researchers created a mouse model with elevated TERT expression in the liver to study its effects during chronic inflammation and found that TERT overexpression accelerates liver tumor development, particularly when the p53 tumor suppressor is inactive.
  • TERT enhances NFκB activity and promotes cell cycle progression by degrading the p21 protein, leading to increased expression of cell cycle-related molecules in HCC tissues, suggesting a direct link between TERT dysregulation and the progression of liver cancer
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Glasdegib is a potent, selective, oral inhibitor of the hedgehog signaling pathway. In this phase I study, previously untreated Japanese patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes were treated with glasdegib (100 mg once daily) combinations: low-dose cytarabine (20 mg twice daily; cohort 1, n = 6; expansion cohort, n = 15); daunorubicin and cytarabine (60 mg/m i.v.

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  • ALS is a serious neurodegenerative disease that urgently requires new treatment options, prompting the investigation of the Src/c-Abl inhibitor bosutinib, originally used for chronic myelogenous leukemia (CML), as a potential therapy for ALS.
  • The study was a phase 1 trial conducted in Japan to assess the safety and tolerability of bosutinib in ALS patients, with participants receiving escalating doses, starting from 100 mg to 400 mg, based on the occurrence of dose-limiting toxicities (DLTs).
  • Results showed that the drug was generally well-tolerated at doses up to 300 mg, with common side effects being gastrointestinal issues, liver function changes, and rashes; however, DLTs occurred at
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Background: Intensivists play an essential role in improving the outcomes of critically ill patients in intensive care units (ICUs). The transition of ICU physician staffing from low-intensity ICUs (elective intensivist or no intensivist consultation) to high-intensity ICUs (mandatory intensivist consultation or a closed ICU) improves clinical outcomes. However, whether a transition from high-intensity to low-intensity ICU staffing affects ICU outcomes and quality of care remains unknown.

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Whether a droplet slides or not on inclined solid surface is mainly influenced by a balance between the adhesion force at contact area and the gravitational force exerted on the droplet. Especially as the adhesion force is a key parameter for the determination of the sliding behavior of droplets. The adhesion force is mainly estimated by experimental observation for the sliding motion of the droplet.

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A man in his 50s was referred to the hospital with fever, right lower abdominal pain, and bloody diarrhea. Based on computed tomography images and characteristic varioliform erosions observed during the colonoscopic examination, the patient was diagnosed with fulminant amebic colitis. Intravenous metronidazole was administered immediately.

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Objectives: Histidine-rich glycoprotein (HRG) and high-mobility group box 1 (HMGB1) regulate the activation of neutrophils and vascular endothelium. The aim of this study was to quantify HRG and HMGB1 levels in patients with Kawasaki disease (KD) and evaluate their use in the clinical management of KD.

Methods: This study was prospectively performed.

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The absolute indications for lower limb replantation are not unequivocally established; rather, this procedure is still challenging and controversial. We report a case of a young male who underwent bilateral leg amputation, followed by unilateral replantation. The patient demonstrated good 10-year outcomes.

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  • Precision medicine customizes healthcare based on individual genetic and clinical factors, yet its use in perioperative management is limited despite known genetic markers linked to anesthetic responses.
  • The study validated six specific SNP loci in Japanese patients using genomic DNA from saliva and compared results from nanopore sequencing to traditional dideoxy sequencing.
  • Findings showed that nanopore sequencing effectively identified genotypes and estimated allele frequencies accurately within a short analysis timeframe, indicating its potential as a reliable tool for SNP genotyping and risk assessment in surgical outcomes.
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  • The study examines antipsychotic prescription trends among Japanese children and adolescents (≤17 years) in outpatient settings from 2006 to 2012, using a large dataset.
  • It found that 65.1% of the patients were aged 13-17 and 52.9% were male, with an increase in second-generation antipsychotic monotherapy prescriptions from 53.8% to 78.3% during the study period.
  • Risperidone was the most commonly prescribed drug, and about 25% of patients received initial doses that were lower than recommended.
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Introduction: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC.

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In event-driven clinical trials comparing the survival functions of two groups, the number of events required to achieve the desired power is usually calculated using the Freedman formula or the Schoenfeld formula. Then, the sample size and the study duration derived from the required number of events are considered; however, their combination is not uniquely determined. In practice, various combinations are examined considering the enrollment speed, study duration, and the cost of enrollment.

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to more than 200 countries. In light of this situation, the Japanese Government declared a state of emergency in seven regions of Japan on 7 April 2020 under the provisions of the law. The medical care delivery system has been under pressure.

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The coronavirus disease 2019 (COVID-19) pandemic is overwhelming Japan's intensive care capacity. This study aimed to determine the number of patients with COVID-19 who required intensive care and to compare the numbers with Japan's intensive care capacity. Publicly available datasets were used to obtain the number of confirmed patients with COVID-19 undergoing mechanical ventilation and extracorporeal membrane oxygenation (ECMO) between 15 February and 19 July 2020 to determine and compare intensive care unit (ICU) and attending bed needs for patients with COVID-19, and to estimate peak ICU demands in Japan.

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Background: Pulmonary vein thrombosis (PVT) and cerebral infarction are rare but critical complications after video-assisted thoracic surgery (VATS).

Case Presentation: We experienced two cases of massive middle cerebral artery infarction after VATS for the left upper lobe. Although the precise source of their embolus was never identified, both cases were clinically suspected PVT.

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The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment-naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression-free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. Japanese patients enrolled in the study (N = 67) were randomized to receive avelumab + axitinib (N = 33) or sunitinib (N = 34); 67% vs 59% had PD-L1+ tumors (≥1% of immune cells) and 6%/64%/27% vs 6%/82%/12% had International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable/intermediate/poor risk status. In patients who received avelumab + axitinib vs sunitinib, median PFS (95% confidence interval [CI]) was not estimable (8.

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Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive and severe neurodegenerative disease caused by motor neuron death. There have as yet been no fundamental curative medicines, and the development of a medicine for ALS is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified an Src/c-Abl inhibitor, bosutinib, as a candidate molecular targeted therapy for ALS.

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Inotuzumab ozogamicin (InO) is a targeted treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). InO was previously studied in INO-VATE, an international, open-label, randomized phase 3 trial comparing InO against standard of care (SoC). In the present subgroup analysis, we evaluated outcomes in the 55 Asian patients who were randomized in INO-VATE (31 InO and 24 SoC).

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Developments in observing system technologies and ocean data assimilation (DA) are symbiotic. New observation types lead to new DA methods and new DA methods, such as coupled DA, can change the value of existing observations or indicate where new observations can have greater utility for monitoring and prediction. Practitioners of DA are encouraged to make better use of observations that are already available, for example, taking advantage of strongly coupled DA so that ocean observations can be used to improve atmospheric analyses and vice versa.

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Warfarin is a drug used for anticoagulation management, with a narrow therapeutic range and multiple drug-drug interactions. Adherence and proper use of concomitant medication are thus fundamental to the efficacy and safety of warfarin therapy. In 2012, we retrospectively analyzed data from three large-scale pharmacy chains in Japan.

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  • A phase II study explored the effects of axitinib dose titration on overall survival in patients with metastatic renal cell carcinoma, revealing potential clinical benefits for treatment-naïve individuals.
  • Researchers analyzed baseline characteristics to see how they influenced overall survival, finding significant distinctions between patients who lived beyond 24 months and those who did not.
  • Key findings included that patients with longer survival had fewer metastatic sites, better blood counts, and a longer time between diagnosis and treatment, while disease progression was the main reason for stopping treatment in both survival groups.
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Hassall's corpuscles (HCs) are composed of cornifying, terminally differentiated medullary thymic epithelial cells (mTECs) that are developed under the control of Aire. Here, we demonstrated that HC-mTECs show features of cellular senescence and produce inflammatory cytokines and chemokines including CXCL5, thereby recruiting and activating neutrophils to produce IL-23 in the thymic medulla. We further indicated that thymic plasmacytoid dendritic cells (pDCs) expressing IL-23 receptors constitutively produced Ifna, which plays a role in single positive (SP) cell maturation, in an Il23a-dependent manner.

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Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice.

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