Publications by authors named "Takahiro Kodama"

In this study, we experimentally demonstrate a PPLN-based free-space to SMF (single-mode fiber) conversion system capable of efficient long-wavelength down-conversion from 518 nm, optimized for minimal loss in highly turbid water, to 1540 nm, which is ideal for low-loss transmission in standard SMF. Leveraging the nonlinear optical properties of periodically poled lithium niobate (PPLN), we achieve a wavelength conversion efficiency of 1.6% through difference frequency generation while maintaining a received optical signal-to-noise ratio of 10.

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Hepatocellular carcinoma presents strong sexual dimorphism, being 2-3 times more frequent in males than in females; however, the role of sex in response to immunotherapies in HCC remains unknown. We demonstrate that NOTCH1, an understudied oncogene in HCC, elicits sexually dimorphic anti-tumor immunity and response to FDA-approved immunotherapies. Surprisingly, males harboring NOTCH1-driven tumors displayed enhanced anti-tumor immune responses, which, in mice, were mediated by dendritic and T cells.

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Aim: The incidence of and factors involved in gastroesophageal varix-related events in hepatitis C virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear.

Methods: We conducted a multicenter study using prospective data from 478 hepatitis C virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria.

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Regular exercise is believed to suppress cancer progression. However, the precise molecular mechanisms by which exercise prevents cancer development remain unclear. In this study, using a steatosis-associated liver cancer mouse model, we found that regular exercise at a speed of 18 m/min for 20 min daily suppressed liver cancer development.

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Article Synopsis
  • Researchers developed a new mouse model to study chronic hepatitis B (CHB) by delivering the HBV genome and a key enzyme, allowing for detailed immune profiling in a lab setting.
  • The CHB mice showed ongoing HBV infection and had signs of exhausted immune cells, with treatments using IFNα and a TLR7 agonist leading to viral suppression and immune enhancement.
  • This study's mouse model mimics immune exhaustion seen in CHB patients and suggests that targeted treatments could help restore immune function against HBV.
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Objectives: In Japan, population-based epidemiological data on respiratory syncytial virus (RSV) infections are limited. To elucidate the epidemiology of RSV before the introduction of new prophylactic drugs, we conducted a population-based study during and after the SARS-CoV-2 pandemic.

Methods: This study was performed in four hospitals in Chiba City and three hospitals in Ichihara City.

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Aim: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C.

Methods: We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.

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Background: There is a need for novel noninvasive markers for metabolic dysfunction-associated steatotic liver disease (MASLD) to stratify patients at high risk for liver-related events including liver cancer and decompensation. In the present study, we used proteomic analysis of proteins in extracellular vesicles (EVs) to identify new biomarkers that change with fibrosis progression and can predict the development of liver-related events.

Methods: We analyzed serum EVs from 50 patients with MASLD assessed for liver fibrosis by biopsy and identified proteins that altered with advanced fibrosis.

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Article Synopsis
  • A recent study explored the use of serum growth differentiation factor-15 (GDF15) as a biomarker to identify high-risk patients with metabolic dysfunction-associated steatotic liver disease (MASLD) who need closer follow-up for liver cancer.
  • Researchers analyzed GDF15 levels in over 500 MASLD patients and found that high levels were linked to increased liver cancer risk, regardless of fibrosis stage or standard risk indicators like the Fib-4 index.
  • The findings suggest that GDF15 could be a convenient and effective indicator for determining which MASLD patients should undergo regular monitoring for liver cancer, thus potentially improving patient outcomes.
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Obesity is a risk factor for pancreatic cancer development, partly due to the tissue environment of metabolic disorder-related inflammation. We aimed to detect a tissue environment marker triggered by obesity-related metabolic disorders related to pancreatic cancer progression. In murine experiments, Bl6/j mice fed a normal diet (ND) or a high-fat diet (HFD) were orthotopically injected with mPKC1, a murine-derived pancreatic cancer cell line.

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This review examines the latest epidemiological and molecular pathogenic findings of metabolic-associated hepatocellular carcinoma (HCC). Its increasing prevalence is a significant concern and reflects the growing burden of obesity and metabolic diseases, including metabolic dysfunction-associated steatotic liver disease, formerly known as nonalcoholic fatty liver disease, and type 2 diabetes. Metabolic-associated HCC has unique molecular abnormality and distinctive gene expression patterns implicating aberrations in bile acid, fatty acid metabolism, oxidative stress, and proinflammatory pathways.

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Article Synopsis
  • Approximately 250 million people globally are chronically infected with hepatitis B virus (HBV), which is linked to liver cancer but its integration into cancer cells isn't fully understood.
  • Researchers aimed to find vulnerability factors related to HBV-infected liver cancer using CRISPR technology, focusing on the differences between normal and HBV-integrated liver cells.
  • Four key genes were identified as potential vulnerability factors, with INSIG2 playing a significant role in inhibiting cell growth specifically in HBV-integrated liver cells by causing cell cycle arrest through a CDK2-dependent mechanism.
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  • - This study evaluated the effectiveness and safety of atezolizumab plus bevacizumab in treating unresectable hepatocellular carcinoma in real-world settings, involving 222 patients from 19 hospitals.
  • - The findings revealed an objective response rate of 22.0% and a median progression-free survival of 5.7 months, with certain factors (like younger age, more tumors, and macrovascular invasion) linked to shorter progression-free survival.
  • - Despite a median overall survival not being reached, key risk factors for reduced survival included absence of hyperlipidemia, multiple intrahepatic tumors, macrovascular invasion, and elevated neutrophil-to-lymphocyte ratios, with 36.0% of
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  • The study investigates the effects of the COVID-19 pandemic on the diagnosis and treatment of hepatocellular carcinoma (HCC) in Japan from January 2019 to December 2021.
  • There was a notable decline in HCC-related medical practices during Japan's first state of emergency in April-May 2020, resulting in fewer new diagnoses of HCC compared to previous and later periods.
  • Despite the decrease in diagnoses, the pandemic did not negatively impact tumor progression or treatment times for HCC patients.
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  • The study analyzed 206 patients with decompensated cirrhosis due to hepatitis C treated with direct-acting antivirals (DAA) from February 2019 to December 2021 in Japan.
  • Patients were mostly older, with 76% classified as Child-Pugh class B (CP-B), and the survival rates were promising, with high 2- and 3-year liver transplantation (LT)-free survival rates.
  • The research found that liver function, assessed at 12 weeks after DAA treatment, was a crucial predictor of prognosis, rather than the baseline liver function at the start of treatment.
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Background: Pancreatitis is known to be an important risk factor for pancreatic ductal adenocarcinoma (PDAC). However, the exact molecular mechanisms of how inflammation promotes PDAC are still not fully understood. Regnase-1, an endoribonuclease, regulates immune responses by degrading mRNAs of inflammation-related genes.

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Aim: Alterations in microbial composition of gut microbiota due to antibiotics (ATB) may lead to resistance to immune checkpoint inhibitors (ICIs). This study aimed to assess the impact of ATB use on therapeutic response in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab.

Methods: This study retrospectively analyzed 105 patients with HCC treated with atezolizumab plus bevacizumab as a primary systemic therapy from prospectively-registered, multicenter, cohorts.

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We evaluated the value of secreted glycoprotein thrombospondin-2 (TSP-2) to predict hepatocellular carcinoma (HCC) occurrence in chronic hepatitis C (CHC) patients after Hepatitis C virus (HCV) elimination by direct-acting antiviral agents (DAAs). A total of 786 CHC patients without an HCC history who achieved a sustained virological response (SVR) with DAAs were randomly assigned 2:1, with 524 patients as the derivation cohort and 262 patients as the validation cohort. Serum TSP-2 levels at the end of treatment were measured by enzyme-linked immunosorbent assay (ELISA).

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Background: Patients with advanced fibrosis are at risk for developing hepatocellular carcinoma (HCC) even after hepatitis C virus (HCV) elimination. We previously reported that serum fucosylated haptoglobin (Fuc-Hp) levels increase as the disease progresses from chronic hepatitis to cirrhosis and then HCC. However, it remains unclear whether serum Fuc-Hp levels can stratify the risk of HCC occurrence after a sustained virological response (SVR) is achieved with direct-acting antivirals (DAAs) in patients with advanced liver fibrosis.

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Background And Aim: Liver function can be improved in patients with chronic hepatitis C virus (HCV) infection who achieved sustained virologic response (SVR) with direct-acting antiviral (DAA) treatment. However, to our knowledge, the impact of liver function improvement after SVR on prognosis has not been investigated.

Methods: A total of 716 patients with chronic HCV infection and compensated advanced liver fibrosis who began receiving DAA treatment between September 2014 and August 2018 in 25 Japanese hospitals and achieved SVR were enrolled.

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Article Synopsis
  • The study aimed to evaluate how direct-acting antiviral therapy affects the long-term health outcomes of patients with decompensated cirrhosis caused by hepatitis C virus.
  • It compared 37 patients undergoing treatment with sofosbuvir and velpatasvir (SOF/VEL) to a historical control group of 65 untreated patients, focusing on rates of liver decompensation, hospitalization, and survival.
  • Results showed that the treatment group had significantly fewer decompensated events and better survival rates over two years, but the risk of developing hepatocellular carcinoma (HCC) was still high in both groups.
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This study proposed a new small star topology network architecture connecting a secondary fiber link between adjacent small cell base stations for disaster tolerance in the access span of a short-reach point-to-multipoint optical communication system. Compared to the edge-side optical node independent architecture, the proposed network architecture exhibits a high robustness and small number of optical components. We compared the conventional and proposed configurations for survivability in the case of a major disaster with a triple-link failure.

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Background & Aims: Signal transducer and activator of transcription 3 (STAT3) is known as a pro-oncogenic transcription factor. Regarding liver carcinogenesis, however, it remains controversial whether activated STAT3 is pro- or anti-tumorigenic. This study aimed to clarify the significance and mechanism of STAT3 activation in hepatocellular carcinoma (HCC).

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