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Background: Although Japan is a major endemic area for human T-lymphotropic virus type 1 (HTLV-1) and the virus has been well-studied in this region, there is limited research on HTLV-1 in surrounding regions. In this study, we determined the complete genome sequences of HTLV-1 strains isolated from Taiwan and Japan and investigated the geographic characteristics of molecular subgroups and substitution mutations to understand the spread of HTLV-1 and its correlation with human migration. Methodology/Principal findings: The complete genome sequences of 26 HTLV-1 isolates from Taiwan were determined using next-generation sequencing and were compared with those of 211 isolates from Japan in terms of subgroup and genetic mutations. In total, 15/26 (58%) isolates from Taiwan belonged to the transcontinental subgroup and 11/26 (42%) isolates belonged to the Japanese subgroup. The transcontinental subgroup was significantly more prevalent among Taiwanese isolates than Japanese isolates (58% vs 18%, P < 0.0001). The mutation rate for the complete HTLV-1 sequence was as low as 0.2%. On examining individual base substitutions, the G-to-A mutation was predominant. Bayesian phylogenetic tree analysis estimated the time to the most recent common ancestor for the transcontinental and Japanese subgroups to be 28447 years. The transcontinental subgroups from Taiwan and Japan appeared to form clusters according to their respective regions. Conclusions/Significance: The transcontinental subgroup of HTLV-1 is predominant in Taiwan, while the Japanese subgroup is common in Japan. The difference in subgroup distribution may be attributed to the initial spread of the transcontinental subgroup in East Asia, followed by the influx of the Japanese subgroup. Author summary: Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects 5–10 million people worldwide. HTLV-1 infection can cause serious diseases including hematologic malignancy, adult T-cell leukemia/lymphoma (ATL), and progressive neurologic disease known as HTLV-1-associated myelopathy/tropical spastic paraplegia (HAM/TSP). An increase in the mortality rate among HTLV-1-infected individuals has become an issue of concern in recent years. Differences in HTLV-1 infection rates and subgroup distribution are considered to be caused by the historical global movement of HTLV-1-infected individuals. Furthermore, recent global population movements have resulted in the redistribution of HTLV-1-infected individuals, which may lead to outbreaks of ATL and HAM/TSP in non-endemic areas. In this study, we investigated the molecular characteristics of HTLV-1 in East Asia and found that the transcontinental subgroup was more prevalent in Taiwan, whereas the Japanese subgroup was common in Japan. The difference in subgroup distribution may be attributed to the initial spread of the transcontinental subgroup in East Asia, followed by the influx of the Japanese subgroup. [ABSTRACT FROM AUTHOR]

Background Guselkumab has demonstrated favourable safety and efficacy across individual clinical studies in adults with moderate-to-severe plaque psoriasis. Objectives To evaluate the safety of guselkumab in patients with psoriasis using pooled data from seven phase II/III studies (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan registration). Methods All studies, except NAVIGATE and ECLIPSE (active comparator-controlled only), included a 16-week placebo-controlled period; X-PLORE, VOYAGE 1 and VOYAGE 2 included both placebo and active controls. In most studies, guselkumab-treated patients received 100-mg subcutaneous injections at week 0, week 4, and then every 8 weeks thereafter. Safety data were summarized for the placebo-controlled period (weeks 0–16) and through the end of the reporting period (up to 5 years). Incidence rates of key safety events were integrated post hoc, adjusted for the duration of follow-up and reported per 100 patient-years (PY). Results During the placebo-controlled period, 544 patients received placebo (165 PY) and 1220 received guselkumab (378 PY). Through the end of the reporting period, 2891 guselkumab-treated patients contributed 8662 PY of follow-up. During the placebo-controlled period, in the guselkumab and placebo groups, respectively, rates of adverse events (AEs) were 346/100 PY and 341/100 PY, and infections were 95.9/100 PY and 83.6/100 PY. Rates of serious AEs (6.3/100 PY vs. 6.7/100 PY), AEs leading to discontinuation (5.0/100 PY vs. 9.7/100 PY), serious infections (1.1/100 PY vs. 1.2/100 PY), malignancy (0.5 patients/100 PY vs. 0.0 patients/100 PY) and major adverse cardiovascular events (MACE; 0.3/100 PY vs. 0.0/100 PY) were low and comparable between guselkumab and placebo. Through the end of the reporting period, safety event rates were lower than or comparable to the placebo-controlled period in guselkumab-treated patients: AEs, 169/100 PY; infections, 65.9/100 PY; serious AEs, 5.3/100 PY; AEs leading to discontinuation, 1.6/100 PY; serious infections, 0.9/100 PY; malignancy, 0.7/100 PY; and MACE, 0.3/100 PY. There were no cases of Crohn disease, ulcerative colitis, opportunistic infection or active tuberculosis related to guselkumab. Conclusions In this comprehensive analysis of 2891 guselkumab-treated patients with psoriasis followed for up to 5 years (8662 PY), guselkumab demonstrated favourable safety, consistent with previous reports. Safety event rates in guselkumab-treated patients were similar to those observed with placebo and were consistent throughout long-term treatment. [ABSTRACT FROM AUTHOR]

Background: Mapping disease rates is an important aspect of epidemiological research because it helps inform public health policy. Disease maps are often drawn according to local administrative areas (LAAs), such as counties, cities, or towns. In LAAs with small populations, disease rates are unstable and are prone to appear extremely high or low. The empirical Bayes methods consider variance differences among different LAAs, thereby stabilizing the disease rates. The methods of kriging break the constraints of geopolitical boundaries and produce a smooth curved surface in the form of contour lines, but the methods lack the stabilizing effect of the empirical Bayes methods., Methods: An easy-to-implement stabilized kriging method is proposed to map disease rates, which allows different errors in different LAAs., Results: Monte Carlo simulations revealed that the stabilized kriging method had smaller symmetric mean absolute percentage error than three other types of methods (the original LAA-based method, empirical Bayes methods, and traditional kriging methods) in nearly all scenarios considered. Real-world data analysis of oral cancer incidence rates in men from Taiwan demonstrated that the age-standardized rates in the central mountainous sparsely-populated region of Taiwan were stabilized using our proposed method, with no more large differences in numerical values, whereas the rates in other populous regions were not over-smoothed. Additionally, the stabilized kriging map had improved resolution and helped locate several hot and cold spots in the incidence rates of oral cancer., Conclusion: We recommend the use of the stabilized kriging method for mapping disease rates.

The Y-chromosome haplogroup C2c1a1a1-M407 is a predominant paternal lineage in Mongolic-speaking populations, especially in Buryats and Kalmyks. However, the origin and internal phylogeny of C2c1a1a1-M407 have not been investigated in detail. In this study, we analyzed twenty-three Y-chromosome sequences of haplogroup C2c1a1a1-M407 and its most closely related clades. We generated a high-resolution phylogenetic tree of haplogroup C2c1a1a1-M407 and its upstream clade C2c1a1-CTS2657, including 32 subclades and 144 non-private Y-chromosome polymorphisms. We discover that all available C2c1a1a1-M407 samples from Mongolic-speaking populations belong to its newly defined downstream clade C2c1a1a1b-F8465, whereas all samples of C2c1a1-CTS2657(xF8465) come from northern Han Chinese, Korean, and Japanese. Furthermore, we observe that C2c1a1a1b-F8465 and its subclade C2c1a1a1b1-F8536 expanded at approximately 0.86 and 0.44 thousand years ago, respectively. Therefore, we conclude that C2c1a1a1-M407 in Mongolic-speaking populations has originated from northeastern Asia. C2c1a1a1b1-F8536, the newly defined subclade of C2c1a1a1-M407, probably represents the genetic relationships between ancient Oyrats, modern Kalmyks, Mongolians, and Buryats.

Few studies have investigated the incidence rate of lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM) in Asian populations. We assessed the incidence of LPL/WM using data from 13 population-based cancer registries in Japan and data from the Taiwan National Cancer registry. During 1996-2003, a total of 280 new cases of LPL/WM were recorded in Japan and 56 were recorded in Taiwan, with the median age at diagnosis being 73 and 67 years, respectively. The incidence of LPL/WM showed male predominance in both countries. Crude age-specific incidence rates increased sharply with age in both countries, especially in people >65 years. Age-standardized (to the World standard population) incidence rates per 100,000 person-years were 0.043 (0.071 for men and 0.023 for women) and 0.031 (0.041 for men and 0.020 for women) in Japan and Taiwan, respectively. Age-standardized (to the 2,000 US standard population) incidence rates in Japan and Taiwan were lower than rates reported in the literature for Asians living in the United State. A significant increasing trend was observed in the incidence over the period from 1996 to 2003 in Japan alone. This report suggests that both environmental and/or genetic factors may be involved in LPL/WM development., (© 2013 UICC.)