市野 直浩

近年,大規模言語モデル(large language models;LLM)が世界的に様々な分野で注目を集めている。LLMとは,非常に巨大なデータセットとディープラーニング技術を用いて構築された言語モデルである。LLMは,人間に近い流暢な会話が可能であら,自然言語を用いたさまざまな処理を高精度で行えることから,世界中で注目を集めている。本研究では,LLMであるOpenAI社が開発したChatGPTの異なる2つのモデル(GPT-3.5,GPT-4)にて,過去3年間の臨床検査技師国家試験におけるChatGPTの正答率について評価を行った。GPT-3.5による正答率の平均は51.4%であった。一方,GPT-4では79.8%の正答率結果が得られた。本結果より,ChatGPTはこの先医療現場における有効なアドバイザーとして進化する可能性をもつことが示唆された。しかし,今回不正解となった20%の中には,患者を診断する際に誤診につながりかねない回答が含まれており,今後のChatGPTの精度向上は必須と考えられる。今回の検証は,LLMにおけるChatGPTの臨床検査領域での多様な応用の進展に寄与すると考えられ,この先の発展に期待したい。(著者抄録)

INTRODUCTION: High-frequency oscillation (HFO) in scalp electroencephalography is a promising new noninvasive prognostic epilepsy biomarker, but further data are needed to ascertain the utility of this parameter. The present work investigated the association between epileptic activity and scalp HFO in pediatric patients with various types of epilepsy, using multivariable regression models to correct for possible confounding factors. METHODS: The authors analyzed 97 subjects who were divided into groups with active epilepsy (within 1 year of seizure), seizure-free epilepsy (>1 year without seizure), and nonepilepsy. Regarding the frequency of seizure occurrence as an indicator of epileptic activity, we categorized subjects into four groups (Daily/Weekly, Monthly, Yearly, and Rarely). RESULTS: Multiple linear regression analysis showed that the scalp HFO detection rate was significantly higher in patients with active epilepsy than in those with nonepilepsy (β [95% confidence interval] = 2.77 [1.79-4.29]; P < 0.001). The association between scalp HFO detection rate and frequency of seizure occurrence was highest in the Daily/Weekly group (β [95% confidence interval] = 3.38 [1.57-7.27]; P = 0.002), followed by Monthly and Yearly groups (β [95% confidence interval] = 2.42 [1.02-5.73]; P = 0.046 and 0.36 [0.16-0.83]; P = 0.017). In addition, HFO duration, number of peaks, and number of channels detected were significantly higher in patients with active epilepsy. CONCLUSIONS: Pediatric patients with active epilepsy and high frequency of seizure occurrence exhibited a higher scalp HFO detection rate. These results may help to establish HFO detectable by noninvasive scalp electroencephalography as a biomarker of active epilepsy in pediatric patients.

Background: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has become a global health problem. NAFLD has few initial symptoms and may be difficult to detect early, so there is need for a minimally invasive early detection marker. We hypothesized that miR-122 and miR-20a levels combined, as the miR-122/miR-20a ratio might detect NAFLD more sensitively. Methods: This study involved 167 participants with low alcohol intake. Those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 44), which was further classified into mild (n = 26) and severe (n = 18) groups based on echogenic intensity and hepatic vessel and diaphragm visualization. Participants without fatty liver were included in the normal group, except for those with an abnormal body mass index, glycated hemoglobin, and systolic blood pressure (n = 123) values. Serum miR-122 and miR-20a expression levels in participants were measured by real-time polymerase chain reaction, and the miR-122/miR-20a was calculated. Results: In the NAFLD group, miR-122 expression was significantly higher and the miR-20a was significantly lower than in the normal group, in agreement with previous studies. miR-122/miR-20a was also significantly higher in the NAFLD group. Receiver operating characteristic curve analysis was performed with miR-122/miR-20a as an NAFLD detection marker, and the area under the curve of miR-122/miR-20a was significantly larger than that of miR-122 or miR-20a alone. Conclusions: The miR-122/miR-20a ratio, combined with miR-122 and miR-20a levels, is a useful biomarker to detect NAFLD with high sensitivity.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global health problem. In recent years, the inhibitory effect of brain-derived neurotrophic factor (BDNF) on diabetes mellitus and fatty liver has been clarified. The purpose of this study was to analyze the relationship between serum BDNF and NAFLD which caused by abnormal metabolism of glucose and lipids. This cross-sectional study involved 429 participants (mean age, 63.5 years: men, 38.5%) with low alcohol intake. Of the participants, those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 88), and the others were classified as the normal (n = 341) group. The NAFLD group was further classified into a mild group (n = 60) and a severe group (n = 28) based on the intensity of echogenicity and visualization of the hepatic vessels and diaphragm. Median BDNF levels were higher in the NAFLD group than the normal group (35.5 vs. 42.3 ng/mL, p < 0.01). Furthermore, BDNF levels tended to be associated with the severity of NAFLD (p < 0.01). In addition to the univariate analysis, in the sex- and age-adjusted model, there was a significant association between the BDNF levels and NAFLD severity (p < 0.01). The fully adjusted regression analysis also showed a positive association between the serum BDNF level and NAFLD (p < 0.01). These results suggest that NAFLD patients have a compensatory increase in circulating BDNF levels.

BACKGROUND: There is limited evidence regarding the relationship between Diabetes mellitus (DM) in middle age and mild cognitive impairment after a follow-up. Therefore, we investigated the relationship between fasting blood glucose (FBG) levels in middle age and cognitive function (assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) in later life, following over 15 years of follow-up in the Aichi Workers' Cohort Study in Japan. METHODS: Participants were 253 former local government employees aged 60-79 years in 2018 who participated in a baseline survey conducted in 2002. Using baseline FBG levels and self-reported history, participants were classified into the normal, impaired fasting glucose (IFG) and, and DM groups. Total MoCA-J score ranges from 0 to 30, and cognitive impairment was defined as MoCA-J score ≤25 in this study. A general linear model was used to estimate the mean MoCA-J scores in the FBG groups, adjusted for age, sex, educational year, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, total cholesterol, and estimated glomerular filtration rate. RESULTS: The mean MoCA-J score in the total population was 25.0, and the prevalence of MoCA-J score ≤25 was 49.0%. Multivariable-adjusted total MoCA-J scores were 25.2, 24.8, and 23.4 in the normal, IFG, and DM groups, respectively. The odds ratio of MoCA-J score ≤25 in the DM group was 3.29. CONCLUSIONS: FBG level in middle age was negatively associated with total MoCA-J scores assessed later in life, independent of confounding variables.

本学では、臨床検査技師教育課程において人体解剖実習を導入し、その有効かつ有益な教育方法を考察した。その結果、「心臓の構造を理解できた」と回答した学生は96%であり、他臓器においても80%以上と高率であった。また、医療職として必須の倫理的教育効果についても「ご遺体の尊厳についての理解」に関して96%の学生から肯定的な回答が得られた。一方で、教員の不足等による不満もあったが、今後は大学院生や勉学の意識の強い卒業生の実習参加などを通して、より広くかつ意義深い実習にしていきたいと考えている。(著者抄録)

Purpose It has been demonstrated that circulating microRNA profiles are affected by physiological conditions. Several studies have demonstrated that microRNAs play important roles in the regulation of adiposity. However, few have investigated the relationship between circulating microRNAs and obesity, which has become a major public health problem worldwide. This study investigated the association between circulating microRNAs and obesity in a Japanese population. Methods Obesity parameters, such as subcutaneous and visceral fat adipose tissue, body fat percentage, and body mass index were assessed in a cross-sectional sample of 526 participants who attended health examinations in Yakumo, Japan. In addition, five circulating microRNAs (miR-20a, -21, -27a, -103a, and -320), which are involved in adipocyte proliferation and differentiation, were quantified using real-time polymerase chain reaction amplification. Results We compared the circulating microRNA concentrations in a percentile greater than 75th (high) with below the value (low) of subcutaneous adipose tissue, visceral fat adipose tissue, body mass index, and per cent body fat. For visceral fat adipose tissue, significant decrease in miR-320 expression was observed in high group. Also, for body mass index, significant change of miR-20a, -27a, 103a, and 320 expression level was observed in high group. Multiple linear regression analysis demonstrated that circulating levels of some microRNA such as miR-27a were significantly associated with subcutaneous adipose tissue, visceral fat adipose tissue, and body mass index. Conclusions Our findings support the need for further studies to determine whether such changes are consistent across different populations and whether the identified microRNAs may represent novel biomarkers to predict the susceptibility and progression of obesity-related disorders.

AimGenome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection. MethodsThe SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. ResultsIn 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG+GG had significantly lower hepatitis B core-related antigen levels (P=0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P=0.0433), and less frequent HCC development (P=0.0256) than those with genotype AA. Multivariate analysis selected age (P=0.0460), platelet count (P=0.0481), -glutamyl transpeptidase (P=0.0030), and nucleotide/nucleoside analog treatment (P=0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P&lt;0.0001), a higher prevalence of HBV genotype C (P=0.0063), and a lower prevalence of the wild-type basal core promoter region (P=0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P&lt;0.0001), platelet count (P=0.0021), HBV DNA levels (P=0.0314), wild type of precore region (P=0.0015), and rs7453920 (P&lt;0.0001) as factors independently associated with HBsAg levels. ConclusionThis study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

北海道八雲町の検診受診者526名(男性219名、女性307名、39歳以上)を対象に、喫煙状況と各種microRNA(miRNA)発現との関連について検討した。定量的リアルタイムPCR法により血清miRNA発現を調べた。非喫煙者を基準として、元喫煙者と喫煙者の血清miRNAのオッズ比を算出した。lethal(let)-7d、miRNA(miR)-150、miR-192、miR-320の発現は喫煙者が非喫煙者よりも有意に多かった。多変量ロジスティック回帰分析により、喫煙者はmiRNA let-7d、miR-21、miR-122、miR-146、miR-150、miR-192、miR-197、miR-320の血清レベルが非喫煙者よりも有意に上昇しているのに対して、元喫煙者はmiR-1、miR-146、miR-150、miR-195、miR-320の血清レベルのオッズ比が有意に高かった。喫煙は各種血清miRNAの発現亢進と関連していることが示された。

はじめに:B型慢性肝炎の病態把握には線維化の程度を的確に診断することが重要である。B型慢性肝炎患者におけるVirtual Touch Quantification(VTQ)による肝硬度の有用性を検討した。対象:2009年〜2015年までに肝硬度測定を行ったB型肝炎患者339例(男性188例、病理組織診断:46例)を対象とした。方法:肝硬度の測定は、右肋間走査にて計10回行い中央値(Vs;m/s)を用いて検討を行った。結果:Vs値と各線維化マーカーを比較するとAPRI、ヒアルロン酸、PT、FIB-4、血小板との間に有意な相関(ρ=0.578、0.497、-0.486、0.438、-0.336)を認めた(p<0.0001)。各線維化stage別のVs値はF0-1(n=10):1.19(1.00-1.59)、F2(n=18):1.29(1.20-1.59)、F3(n=11):1.54(1.39-2.24)、F4(n=7):2.31(1.94-2.69)であり、F4はF0-1、F2に比べ有意に高値を示した(p=0.0155、0.0027)。また各stageのカットオフ値はF2以上:1.16、F3以上:1.36、F4:1.82であった。考察:VTQによるVs値測定は、各種線維化マーカーおよび肝線維化stageと良好な相関関係があり、さらに肝線維化stageと最もよく相関しており、肝線維化評価に有用と思われた。(著者抄録)

AIM: To evaluate the changes of shear-wave velocity (Vs) by acoustic radiation force impulse after treatment in chronic hepatitis C. METHODS: Eighty-seven patients with chronic hepatitis C were consecutively treated with combinations of interferon (IFN) plus ribavirin (RBV). Vs value (m/s) was measured with acoustic radiation force impulse before treatment, at end of treatment (EOT), 1 year after EOT, and 2 years after EOT. RESULTS: In patients with a sustained virological response (SVR) (n = 41), Vs significantly decreased at EOT [1.19 (1.07-1.37), P = 0.0004], 1 year after EOT [1.10 (1.00-1.22), P = 0.0001], and 2 years after EOT [1.05 (0.95-1.16), P &lt; 0.0001] compared with baseline [1.27 (1.11-1.49)]. In patients with a relapse (n = 26), Vs did not significantly decrease at EOT [1.23 (1.12-1.55)], 1 year after EOT [1.20 (1.12-1.80)], and 2 years after EOT [1.41 (1.08-2.01)] compared with baseline [1.39 (1.15-1.57)]. In patients with a nonvirological response (n = 20), Vs did not significantly decrease at EOT [1.64 (1.43-2.06)], 1 year after EOT [1.66 (1.30-1.95)], and 2 years after EOT [1.61 (1.36-2.37)] compared with baseline [1.80 (1.54-2.01)]. Among genotype 1 patients, baseline Vs was significantly lower in SVR patients [1.28 (1.04-1.40)] than in non-SVR patients [1.56 (1.20-1.83)] (P = 0.0142). CONCLUSION: Reduction of Vs values was shown in SVR patients after IFN-plus-RBV therapy by acoustic radiation force impulse.

Background: Circulating microRNAs (miRs) may be promising biomarkers for several diseases. We previously found that miR-122 can function as a biomarker for non-alcoholic fatty liver disease (NAFLD). However, little is known regarding the time course of circulating miR-122 levels during the development of NAFLD. Here, we examined circulating miR-122 levels using a rat model of NAFLD. Methods: To clarify changes in serum levels of miR-122 during development of NAFLD, experimental rats were fed a high-fat diet (HFD) for 2-10 weeks, while control rats received standard chow. Serum and liver tissue was collected from all animals at 2, 6, and 10 weeks of feeding. Clinical laboratory parameters (cholesterol, TG, AST, ALT, NEFA) were determined by biochemistry analyzer. Hepatic lipid accumulation was estimated by Oil red 0 staining. Circulating miR-122 levels were then measured by real-time polymerase chain reaction. Results: Over the 10 weeks of feeding, body weight, total liver lipids, and liver and serum triacylglycerol were increased in the HFD group compared to the control group. However, no significant changes in serum alanine aminotransferase activity were observed, suggesting that NAFLD status was mild. In contrast, we observed drastic up-regulation of circulating miR-122 levels. Our findings suggest that serum miR-122 level is indeed useful for assessing early NAFLD and might be superior to clinical markers traditionally used to monitor hepatic disease. (C) 2015 Elsevier B.V. All rights reserved.

Aim: To investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients. Methods: Two hundred and thirty-one patients with CHC were examined for PNPLA3 genotypes, liver stiffness measurements (LSM), and hepatocellular carcinoma (HCC) from May 2010 to October 2012 at Fujita Health University Hospital. The rs738409 single nucleotide polymorphism (SNP) encoding for a functional PNPLA3 I148M protein variant was genotyped using a TaqMan predesigned SNP genotyping assay. LSM was determined as the velocity of a shear wave (Vs) with an acoustic radiation force impulse. Vs cut-off values for cirrhosis were set at 1.55 m/s. We excluded CHC patients with a sustained virological response or relapse after interferon treatment. Results: PNPLA3 genotypes were CC, CG, and GG for 118, 72, and 41 patients, respectively. Multivariable logistic regression analysis selected older age (OR = 1.06; 95% CI: 1.03-1.09; p &lt; 0.0001), higher body mass index (BMI) (OR= 1.12; 95% CI: 1.03-1.22; p = 0.0082), and PNPLA3 genotype GG (OR = 2.07; 95% CI: 0.97-4.42; p = 0.0599) as the factors independently associated with cirrhosis. When 137 patients without past history of interferon treatment were separately assessed, multivariable logistic regression analysis selected older age (OR = 1.05; 95% CI: 1.02-1.09; p = 0.0034), and PNPLA3 genotype GG (OR = 3.35; 95% CI: 1.13-9.91; p = 0.0291) as the factors independently associated with cirrhosis. Multivariable logistic regression analysis selected older age (OR = 1.12; 95% CI: 1.07-1.17; p &lt; 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15-5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90-3.71); p = 0.0936) as the factors independently associated with HCC. Conclusion: PNPLA3 genotype I148M is one of risk factors for developing HCC in Japanese CHC patients, and is one of risk factors for progress to cirrhosis in the patients without past history of interferon treatment.