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日本人若年女性におけるHPVワクチン接種のHPV感染に対する長期有効性 : リアルワールドデータ
Get PDF新潟大学Niigata University博士（医学）In Japan, public funding for HPV vaccination began in 2010 for girls aged 13–16 years (birth cohort years 1994–1997) and women born in 1994 who turned 25 in 2019. We aimed to verify the long-term effectiveness of the bivalent HPV vaccine in women aged 25 years. Subjects were women aged 25–26 years who underwent cervical can-cer screening and HPV testing in Niigata from 2019 to 2020 (birth cohort years 1993–1994). Information on vaccination status and sexual behavior was obtained from a questionnaire and municipal records. We compared the HPV infection rates of the vac-cinated and unvaccinated groups. Of the 429 registrants, 150 (35.0%) and 279 (65.0%) were vaccinated and unvaccinated, respectively. The average period from HPV vaccination to HPV testing was 102.7 months (8.6 years), with a median of 103 months (range 92–109 months). The HPV high-risk infection rate was 21.3% (32/150) in the vaccinated group and 23.7% (66/279) in the unvaccinated group (P = 0.63). The HPV16/18 infection rate was 0% (0/150) in the vaccinated group and 5.4% (15/279) in the unvaccinated group, showing a significant difference (P = 0.0018), and the vac-cine effectiveness was 100%. The cross-protective type HPV31/45/52 infection rate in the vaccinated group was significantly lower than that in the unvaccinated group (3.3% vs. 10.0%, P = 0.013). There was no significant difference in the mean age at sexual debut and the number of previous sexual partners between the two groups. We have demonstrated the long-term 9-year effectiveness of the bivalent vaccine against HPV infection for the first time in Japan.Kurosawa M, Sekine M, Yamaguchi M, et al. Long-term effectiveness of HPV vaccination against HPV infection in young Japanese women: Real-world data. Cancer Sci. 2022; 113: 1435–1440. doi:10.1111/cas.15282新大院博（医）第1213
酵母atg変異体における非選択的および選択的オートファジーの包括的解析とAtg8共役系非存在時のオートファジー活性の特徴解明
Get PDF新潟大学Niigata University博士（医学）Most autophagy-related genes, or ATG genes, have been identified through studies using budding yeast. Although the functions of the ATG genes are well understood, the contributions of individual genes to non-selective and various types of selective autophagy remain to be fully elucidated. In this study, we quantified the activity of non-selective autophagy, the cytoplasm-to-vacuole targeting (Cvt) pathway, mitophagy, endoplasmic reticulum (ER)-phagy and pexophagy in all Saccharomyces cerevisiae atg mutants. Among the mutants of the core autophagy genes considered essential for autophagy, the atg13 mutant and mutants of the genes involved in the two ubiquitin-like conjugation systems retained residual autophagic functionality. In particular, mutants of the Atg8 ubiquitin-like conjugation system (the Atg8 sys-tem) exhibited substantial levels of non-selective autophagy, the Cvt pathway and pexophagy, although mitophagy and ER-phagy were undetectable. Atg8-system mutants also displayed intravacuolar vesicles resembling autophagic bodies, albeit at significantly reduced size and frequency. Thus, our data suggest that membranous sequestration and vacuolar delivery of autophagic cargo can occur in the absence of the Atg8 system. Alongside these findings, the comprehensive analysis conducted here provides valuable datasets for future autophagy research.Tamara Ginevskaia, Aleksei Innokentev, Kentaro Furukawa, Tomoyuki Fukuda, Manabu Hayatsu, Shun-ichi Yamashita, Keiichi Inoue, Shinsuke Shibata, Tomotake Kanki, Comprehensive analysis of non-selective and selective autophagy in yeast atg mutants and characterization of autophagic activity in the absence of the Atg8 conjugation system, The Journal of Biochemistry, Volume 176, Issue 3, September 2024, Pages 217–227, https://doi.org/10.1093/jb/mvae042新大院博（医）第1222
ロシアにおける大豆品種の包括的分析 : 大豆品種多様性への洞察
Get PDF新潟大学Niigata University博士（農学）Soybean seeds are known for their high protein content and rich biochemical composition, presenting a promising solution to global challenges in addressing protein deficiency. Comparative analysis of soybean varieties across different countries offers valuable insights into global soybean cultivation practices. In the context of Russia, a country with diverse agricultural landscapes and varying climatic conditions, understanding the diversity of soybean varieties is crucial. The Russian Federation, while constituting approximately 1% of global soybean production, ranks as the seventh largest producer worldwide. In 2023, soybean production in Russia reached 4.6 million tons, cultivated across 3.5 million hectares of arable land. The thesis explores various aspects of soybean breeding in Russia, focusing on historical development, current trends, and future prospects. This study is structured into several significant chapters, each contributing to an important understanding of the topic. The Introduction chapter sets the stage by outlining the importance of soybeans as a global crop, detailing their nutritional value, economic significance, and the role they play in addressing global food security. This section also introduces the primary research objectives and the scope of the study, emphasizing the need for a detailed analysis of soybean breeding within the Russian context. In the Materials and Methods chapter, the study site is described in detail, highlighting Russia's vast geographic and climatic diversity, which has unique challenges and opportunities for soybean cultivation. The chapter outlines the data sources used, including national agricultural databases, and describes the statistical and geospatial analysis methods used to process and visualize the data. The Results and Discussion chapter is the core of the thesis, divided into multiple sub-sections. The first sub-section reviews global trends in soybean production, comparing production volumes, harvested areas, and yield data across major soybean-producing countries. This analysis helps understand Russia's position within the global soybean market. Next sub-section focuses on the trends in soybean production within Russia. It provides information on the historical and current state of soybean farming across various Russian regions. The study identifies the Central Federal District as having the highest yield potential, while the Volga Federal District excels in oil content and the Far Eastern Federal District in protein content of soybean varieties. A significant portion of the chapter is dedicated to analyzing the diversity of soybean varieties registered in Russia. The study traces the origin of these varieties, noting that approximately 40% are of foreign origin, with the Krasnodar and Amur regions being pivotal in the registration of new varieties. The analysis also examines the maturity periods of these varieties and their adaptation to regional climatic conditions. The chapter on Soybean Breeding in the Far East examines the historical development and current practices in the Amur Region, a key area for soybean cultivation in Russia. It highlights the pioneering work of Soviet breeder V.A. Zolotnitsky and the ongoing efforts to develop high-yield, high-protein soybean varieties suited to the region's climatic conditions. The study also includes a comprehensive analysis of Soybean varietal characteristics, discussing yield, protein, and oil content across different regions. This section uses advanced statistical and geospatial techniques to provide a nuanced understanding of how regional climates affect these characteristics. Special attention is given to the soybean industry in the Far East, particularly the Amur Region. The study examines the impact of climate change on soybean cultivation in Russia. It presents data on temperature trends and discusses how these changes influence soybean yields and varietal performance. This section also includes a detailed mapping of active temperature accumulations using the Triangulated Irregular Network (TIN) method. The Import and Export Analysis section provides insights into Russia's role in the global soybean market. It reviews trade data, identifies key importers and exporters, and discusses the competitive landscape of soybean production. The study highlights the increasing demand for non-GMO soybeans from international markets, particularly Japan and China. Overall, this thesis provides a detailed and comprehensive analysis of soybean breeding in Russia, offering valuable insights for researchers, policymakers, and industry stakeholders involved in the global soybean market.Journal of Infrastructure, Policy and Development. 2024, 8(8)新大院博(農)第252
アムール州における大豆生産のための深層施肥播種機の開発
Get PDF新潟大学Niigata University博士（農学）The scientific work discusses the benefits of minimum tillage technology, which involves loosening soil and applying fertilizer below the main crop. This method reduces the operations needed to cultivate row crops like soybeans, wheat, and others. This research aims to enhance crop yields by optimizing the process of fertilization at deeper levels. The study focuses on a machine-tractor unit that is used for pre-sowing fertilization. The subject of the research is to analyze how technological processes and technical tools impact the efficiency of fertilizer application and soybean yield. The developed tool is designed to perform simultaneously such operations as cutting slits in the soil up to 30 cm deep and 2 cm wide. This helps to regulate the water supply to the plant roots. And the arrow-shaped coulter cuts the root system of weeds and loosens the soil at depth. And it applies an additional dose of fertilizer through the seed pipe installed on it. In the research, we used computer simulations to analyze the final model of the soil deepener within a computer-aided manufacturing system (CAD) while considering all operating parameters and conditions. To properly evaluate the model, we conducted a mathematical analysis. As a result, we were able to determine the amount of traction load that impacts the functioning of the soil deepener. The mathematical analysis showed that the traction load affecting one of the tools was 2500 N for black soil and 5000 N for clay soil. The design was analyzed for integrity, identifying points that could cause damage and areas subjected to loads. Structural deformations were analyzed to determine safety factors, concluding that the selected materials and attachment methods meet operational requirements. A field experiment was conducted to reveal the effect of soil deepening and different depths of granular fertilizer application on vegetable soybean yield. The study involved five different treatments for growing vegetable soybeans. Control (no treatment), Compost (spreading manure over the experimental plot of the field with subsequent incorporation into the soil), and 3 treatments of deep fertilizer application (DP) to a depth of 100 mm, 125 mm, and 150 mm, respectively, below the level of the sowing main crop with soil deepening (cutting a slot in the soil). The Enrei soybean variety was planted between May 31st, with a seeding rate of 240-280 thousand germinating seeds per hectare (20-40kg/ha), at a depth of 4-5 cm. In variant 2, compost was applied at a rate of 100 kg/ha. For deep placement, Lime nitrogen (Ca(CN)2) was used, with a dose of 150 kg per hectare. Crop care included harrowing, mechanical treatment of soybean rows, and repeating these steps three times. The experiment was conducted on a 399 m² area, with a plot size of 7 m by 3.8 m (26.6 m²), and randomized plot placement. As a result of the field experiment, we obtained that the DP 100 variant (deep placement) has the greatest prospects for increasing pod yield. Control and DP 100 perform slightly better in 100-seed mass, while Compost, DP 150, and DP 125 show slightly lower values. DP 100 surpasses both vegetable and grain soybean yields, resulting in a 20.63% increase in vegetable soybean yield (1.52 t/ha) and a 15.18% increase in grain soybean yield (1.03 t/ha) compared to the control. DP 125 also exhibits competitive performance, highlighting DP 100's potential effectiveness in enhancing soybean yields. The outcomes of the experiments were utilized in analyzing and executing the last design of the soil deepener tool.新大院博(農)第248
脳腫瘍に伴うのう胞液を対象とした脳腫瘍関連遺伝子変異の検出
Get PDF新潟大学Niigata University博士（医学）Purpose Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was per-formed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. Methods Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Addition-ally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligoden-drogliomas and grading is possible from cyst fluid cfDNA. Results Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Vari-ant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson’s correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. Conclusion Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diag-nosing brain tumors.Journal of Neuro-Oncology. 2024, 166, 273–282.新大院博（医）第1162
圧迫性頚髄症患者における重症度別の歩行解析
Get PDF新潟大学Niigata University博士（医学）Introduction: Gait disturbance due to compressive cervical myelopathy has been previously described. However, data on how gait disturbance varies with the degree of lower extremity motor impairment are limited. Therefore, we investigated the characteristics of gait analysis based on severity and determined how gait disturbance progresses in compressive cervical myelopathy. Methods: We enrolled 44 patients (32 men and 12 women; mean age, 65.0 years) out of 108 consecutive patients with compressive cervical myelopathy who underwent spinal cord decompression surgery in our hospital. The exclusion criteria were inability to gait and complications affecting gait. Twenty-two patients with Japanese Orthopaedic Association scores 1 or 2 for lower extremity motor functions were assigned to the severe group, and 22 patients who scored 3 or 4 were as-signed to the moderate group. Gait analysis was performed preoperatively using a long thin-type sensor sheet, and 25 healthy volunteers were assigned to the control group. Results: Stride length, swing phase, and gait speed decreased whereas step angle, stance phase, and double support dura-tion increased as myelopathy progressed. Step width was significantly larger in the severe group than in the moderate and control groups. The cutoff values based on severe myelopathy with the inability to ascend or descend stairs without support were 60% for the stride length percentage of body height and 100 cm/s for gait speed. Conclusions: Decreases in stride length, swing phase, and gait speed and increases in step angle, stance phase, and dou-ble support duration are compensatory changes as cervical myelopathy progresses. Step width is a compensatory change that is not significantly altered in moderate myelopathy but increases when gait becomes affected, such that the patient can-not ascend or descend stairs without support.Tatsuo Makino, Kei Watanabe, Tatsuki Mizouchi, Takaaki Urakawa, Masayuki Ohashi, Hideki Tashi, Keitaro Minato, Yuki Tanaka, Hiroyuki Kawashima, Gait Analysis by the Severity of Gait Disturbance in Patients with Compressive Cervical Myelopathy, Spine Surgery and Related Research, 2023, Volume 7, Issue 6, Pages 488-495, Released on J-STAGE November 27, 2023, Advance online publication July 06, 2023, Online ISSN 2432-261X, https://doi.org/10.22603/ssrr.2023-0104, https://www.jstage.jst.go.jp/article/ssrr/7/6/7_2023-0104/_article/-char/en新大博（医）第1196
日本の後期高齢者における入院費の地域格差の検討 : 全国データを用いた３階層のマルチレベル分析
Get PDF新潟大学Niigata University博士（医学）Introduction: In Japan, a country at the forefront of population aging, significant geographic variation has been observed in inpatient medical expenditures for older adults aged 75 and above (IMEP75), both at the small- and large-area levels. However, our understanding of how different levels of administrative (geographic) units contribute to the overall geographic disparities remains incomplete. Thus, this study aimed to assess the degree to which geographic variation in IMEP75 can be attributed to municipality-, secondary medical area (SMA)-, and prefecture-level characteristics, and identify key factors associated with IMEP75. Methods: Using nationwide aggregate health insurance claims data of municipalities for the period of April 2018 to March 2019, we conducted a multilevel linear regression analysis with three levels: municipalities, SMA, and prefectures. The contribution of municipality-, SMA-, and prefecture-level correlates to the overall geographic variation in IMEP75 was evaluated using the proportional change in variance across six constructed models. The effects of individual factors on IMEP75 in the multilevel models were assessed by estimating beta coefficients with their 95% confidence intervals. Results: We analysed data of 1,888 municipalities, 344 SMAs, and 47 prefectures. The availability of healthcare resources at the SMA-level and broader regions to which prefectures belonged together explained 57.3% of the overall geographic variance in IMEP75, whereas the effects of factors influencing healthcare demands at the municipality-level were relatively minor, contributing an additional explanatory power of 2.5%. Factors related to long-term and end-of-life care needs and provision such as the proportion of older adults certified as needing long-term care, long-term care benefit expenditure per recipient, and the availability of hospital beds for psychiatric and chronic care and end-of-life care support at home were associated with IMEP75. Conclusion: To ameliorate the geographic variation in IMEP75 in Japan, the reallocation of healthcare resources across SMAs should be considered, and drivers of broader regional disparities need to be further explored. Moreover, healthcare systems for older adults must integrate an infrastructure of efficient long-term care and end-of-life care delivery outside hospitals to alleviate the burden on inpatient care.This article is submitted version of below: Shirakura Y, Shobugawa Y and Saito R (2024) Geographic variation in inpatient medical expenditure among older adults aged 75 years and above in Japan: a three-level multilevel analysis of nationwide data. Front. Public Health. 12:1306013. doi: 10.3389/fpubh.2024.1306013
First publication by Frontiers in Public Health新大博（医）第1200
MPB70 とそのプロモーターを利用した遺伝子組換えは、BCG 東京での効率的な遺伝子発現と分泌を可能とする
Get PDF新潟大学Niigata University博士（医学）新大博（医）第1203