Focusing on the theme of global health and medicine, at the beginning of the new era (Reiwa) in Japan, we are pleased and honored to launch Global Health & Medicine, an international, open-access, peer-reviewed journal, published by the National Center for Global Health and Medicine (NCGM), which is a national research and development agency in Japan that covers advanced general medicine, basic science, clinical science, and international medical collaboration. The journal is dedicated to publishing high-quality original research that contributes to advancing global health and medicine, with the goal of creating a global information network for global health, basic science as well as clinical science oriented for clinical application. We aspire to identify, attract, and publish original research that supports advances of knowledge in critical areas of global health and medicine.

Japan is aging rapidly, and its society is changing. Population aging and social change are mutually linked and appear to form a vicious cycle. Post-war Japan started to invest intensively in infectious disease control by expanding health services and achieving universal medical insurance coverage in 1961. The high economic growth in the 1960s contributed to generate a thick middle class layer, but the lingering economic slump after the economic bubble crisis after 1991 and globalization weakened this segment of society. Health disparity has been acknowledged and social determinates of health have been focused. In this article, the author reviewed the response course to health challenges posed by population aging in Japan, and aims to offer lessons to learn for Asian nations that are also rapidly aging. The core viewpoints include: i) review health policy transformations until the super-aged society, ii) discuss how domestic issues in aging can be a global issue, iii) analyze its relationship with Japanese global health engagement, iv) debate the context of social determinates of health, and v) synthesize these issues and translate to future directions.

The Meetings of Health Ministers of the Group of Twenty (G20) that started at the G20 Summit in Berlin, Germany in 2017 have provided a platform for the discussion of global health matters such as antimicrobial resistance (AMR), public health emergencies, and universal health coverage. Similar issues are also discussed at meetings of the G7 and the World Health Assembly (WHA). This article will examine recent data to explore the characteristics of the G20 and its potential for improving health outcomes. G20 countries have a leading role to play in helping other countries improve global health outcomes because member countries have already faced many issues associated with aging society and increased prevalence of non-communicable diseases (NCDs). Indeed, 71% of the world's elderly population lives in the G20 countries and most of these countries have a high proportional mortality from NCDs of more than 70%. G20 countries are also responsible for a disproportionate share of global impacts. For instance, 72% of CO₂ emissions are produced by G20 countries. Migration dynamics and its consequences also need to be considered from the perspective of optimizing health outcomes. Moreover, 78% of the world's top 50 pharmaceutical companies are located in the G20 countries. There is ample room for G20 countries to pursue collaborative and cooperative approaches that can complement the roles of the G7 and WHA in similar health issues. The G20 could, for example, share experiences on dealing with aging and NCDs, reduce their CO₂ emissions, prohibit the production of lowquality medicines, and use standardized health check-up formats for migrants and refugees to transfer their own health information. As a group, the G20 countries have the potential to solve global health problems and other issues. The convening of high-level health meetings at G20 summits has the potential to facilitate such endeavors.

Based on data from the Chinese Center for Disease Control and Prevention (CDC), there were a total of 861,042 people with human immunodeficiency virus (HIV)/ immune deficiency syndrome (AIDS) as of December 31, 2018 in China, a total of 148,589 new HIV infections, and 38,134 AIDS-related deaths in the year 2018. As of 2017, only 74% of people living with HIV knew their status, 80% of people living with HIV were receiving treatment, and 91% were virally suppressed in China. Although mankind has made great progress in the fight against AIDS in recent years, the vision of ending the AIDS epidemic still faces many challenges in China. Due to the huge population and the imbalance in the prevalence of HIV/AIDS in China, expanding HIV screening and early detection remains the key to China’s response to HIV. Limitations of antiviral therapy (ART), rejection or discontinuation of an immediate ART strategy by people infected with HIV, and the difficult search for a cure for AIDS all limit the coverage and quality of treatment. The high price of drugs and lack of vaccines present enormous challenges; social discrimination still exists, and participation by non-governmental organizations in prevention, treatment, and care is limited. As part of the future response to HIV, HIV eradication programs should continue to be explored, and attention should be paid to long-term care for people living with HIV.

One of the important missions of the Hepatitis Information Center is to disseminate information regarding liver disease. The Hepatitis Information Center, National Center for Global Health and Medicine (NCGM) has been endeavoring to ensure that reliable and up-to-date information on liver disease is accessible to all people, regardless of age, disability, and background. Described here are several initiatives with regard to the dissemination of information about liver disease including: i) Education tool for youth, ii) Conversion of materials on liver diseases into audio format for the visually impaired, and iii) Hepatic Disease Medical Navigation System (Hepatic Navi). Hepatic Navi is a web-based search tool that informs users of the location and other information concerning medical centers where people can be tested for the hepatitis virus for free or at reduced cost. Hepatic Navi consolidates data from 47 prefectures into one database. The system depicts data via an interface that can be accessed anywhere with a PC, tablet, smart phone, or mobile phone. As a result, it has become possible for anyone from anywhere to access information on hepatitis virus testing. By using Hepatic Navi, it is anticipated that general people in need feel free to access to the testing and further treatment for virus hepatitis.

During the last two decades, there has been a dramatic increase in so-called non-B non-C hepatocellular carcinoma (NBNC HCC) in Japan. Majority of NBNC HCC are considered as so-called metabolic HCC and some could be related to occult HBV infection. Although there have been some reports on histological features predominant in metabolic HCC, very few specific driver genes for NBNC HCC have been reported. Most of the NBNC HCC are found incidentally and are relatively large in size. Since liver function is generally normal or subnormal, such patients have a higher chance for undergoing curative surgery. Although there has been slightly conflicting long-term outcomes reported for NBNC HCC, slightly better outcomes may be expected compared to other etiologies after curative surgery. However, risk of recurrence depends on the background liver. NBNC HCC in cirrhotic patients have a persistently higher risk of tumor recurrence requiring a long-term postoperative surveillance. It would be safe to conclude at this moment that NBNC HCCs should be treated using the same surgical strategy as HCCs with viral origin, same operative indications and same follow-up protocol.

Diabetes is one of the well-established independent risk factors for cardiovascular diseases. Diabetes induces dyslipidemia which is characterized by elevated fasting triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C), and such diabetic dyslipidemia is a crucial determinant for atherogenesis and atherosclerotic progression in patients with diabetes. Previous measurement methods of lipoproteins have problems including time-consuming (ultracentrifugation) and inaccurate and impossible measurements of TG-rich lipoproteins such as chylomicron, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL). Our developed anion-exchange high-performance liquid chromatography (AEX-HPLC) can measure all fractions of lipoproteins accurately. Our studies using AEX-HPLC showed that IDL and VLDL in type 2 diabetes were higher than non-diabetic subjects, and IDL and VLDL were higher in the order of type 2 diabetic patients with obesity, type 2 diabetic patients without obesity, and non-diabetic subjects. Here, we also describe the underlying mechanisms for development of diabetic dyslipidemia.

We designed, synthesized, and identified two novel nonpeptidic HIV-1 protease inhibitors (PIs), GRL-037 and GRL-044, containing P2-tetrahydropyrano-tetrahydrofuran (Tp-THF), P1-benzene and P1-methoxybenzene, respectively, and P2'-isopropyl-aminobenzothiazole (Ip-Abt), based on the structure of the prototypic PI, darunavir (DRV). The 50% inhibitory concentrations (IC₅₀s) of GRL-037 and GRL-044 against wild-type HIV-1_NL4-3 were 0.042 and 0.0028-0.0033 nM with minimal cytotoxicity profiles compared to the IC₅₀ values of four most potent FDA-approved PIs, ranging from 2.6 to 70 nM. GRL-044 was also potent against HIV-2_EHO (IC₅₀=0.0004 nM) and various PI-resistant HIV-1 variants (IC₅₀ ranging from 0.065 to 19 nM). In the selection assays we conducted, the emergence of HIV-1 variants resistant to GRL-044 was significantly delayed compared to that against DRV. Thermal stability test using differential scanning fluorimetry employing purified HIV-1 protease (PR) and SYPRO^® Orange showed that both GRL-037 and GRL-044 tightly bound to PR. A28S substitution emerged in the homologous recombination-based selection assays with GRL-044. Structural analyses showed that the larger size of GRL-044 over DRV, enabling GRL-044 to fit better to the hydrophobic cavity of protease, contributed to the greater potency of GRL-044 against HIV-1. Structural analyses also suggested that the van der Waals surface contact of GRL-044 with A28' appears to be better compared to that of DRV because of the larger surface of Ip-Abt of GRL-044, which may be partially responsible for the emergence of A28S. The present antiviral data and structural features of GRL-044 should provide molecular insights for further design and development of potent and "resistance-repellant" novel PIs.

Along improvement of prognosis of HIV-1-infected patients due to successful anti-retroviral therapy, main causes of death in the patients have been changing from AIDS to non-AIDS defining malignancies (NADM) recently. However, little is known about the prevalence and incidence of NADM in patients, and especially in HIV-1-infected hemophiliacs. We prospectively conducted NADM screening with FDG-PET, chest CT, upper gastrointestinal endoscopy, tumor markers, and stool occult blood in hemophiliacs with a mean age of 48.9 years. Screening was done twice from December 2016 through March 2019; the first screening was used to calculate prevalence in 69 patients and the second was used to calculate incidence in 56 patients. The first screening revealed 4 cases of malignancies; three were cases of thyroid cancer and one was a case of a neuroendocrine tumor in the pancreas; prevalence was 5.8% (95% CI: 0.2-11.4%). During a mean follow-up of 1.2 years with 68.2 person-years (PYs), cancer was diagnosed in 2 cases (pancreatic and liver cancer) during the second screening. Incidence was 2.99/100 PY. It can be speculated that there might be around 40 cases of undiagnosed NADM currently and 20 cases of new NADM annually in this population, because 718 HIV-1-infected hemophiliacs are surviving in Japan according to the 2018 Nationwide Survey on Coagulation Disorders. Screening for NADM in HIV-1-infected hemophiliacs at other hospitals is strongly recommended.

In the United States, hepatocellular carcinoma (HCC) incidence rates were approximately three times higher in over 30 years. To investigate the long-term outcomes of patients who underwent resection, ablation, and trans-arterial chemoembolization (TACE) of HCC, we analyzed the National Cancer Data Base (NCDB), which is a nationwide oncology outcomes database and covers approximately 70% of new cancer cases in the United States. A total of 56,512 patients with HCC in the NCDB during 2004-2013 were retrospectively analyzed. Results showed that liver resection (48.5%) and ablation (57.0%) were performed more frequently than TACE (31.5%) in patients with AJCC stage I HCC. The 5-year overall survival (OS) was significantly higher in patients undergoing resection (52.4%) than in patients undergoing ablation (40.5%; P < 0.001) and patients undergoing TACE (36.1%; P < 0.001). For patients with AJCC stage I, the 5-year OS of patients undergoing resection (51.6%; P < 0.001) and patients undergoing ablation (51.1%, P = 0.005) remains significantly better than patients undergoing TACE (40.0%). However, the 5-year OS did not differ significantly between patients undergoing resection and patients undergoing ablation (P = 0.486). Additionally, the findings of our study confirm that the sub-stratification of T1 category by HCC diameter in the AJCC staging eighth edition (i.e., T1a, HCC diameter ≤ 2 cm and T1b, HCC diameter > 2 cm) is valid, with a 5-year OS of 54.1% and 50.4%, respectively (P = 0.031).