Prognostic and diagnostic effects of high serum midkine levels in patients with hepatocellular carcinoma.

Midkine (MK) is a soluble cytokine, and its serum levels strongly correspond to protein expression levels in tumors. The present study aimed to clarify the clinicopathological and prognostic significance of serum MK (s-MK) in patients with hepatocellular carcinoma (HCC). Serum samples were obtained before surgery from 123 patients with HCC who had undergone surgery between January 2012 and December 2020. The receiver operating characteristic curve revealed that the best cut-off value for s-MK in differentiating HCC from healthy cases was 426 pg/ml. The clinicopathological variables and overall survival of patients were compared between the s-MK-positive group and s-MK-negative group. The sensitivity, specificity and accuracy of s-MK were 82.1, 97.4 and 88.0%, respectively. An s-MK-positive status was significantly associated with the number of tumors (≥2). The positivity rate of s-MK was significantly higher compared with that of α-fetoprotein and protein-induced by vitamin K absence-II. In total, only 28% of the patients were positive for s-MK. The s-MK-positive group showed significantly worse overall survival compared with the s-MK-negative group. Moreover, multivariate analysis revealed that an s-MK-positive status was independently associated with poor prognosis. s-MK was useful in detecting early HCC. The findings of this study indicated that the s-MK-positive status is associated with the number of tumors and can act as an independent prognostic risk factor.

Explainable artificial intelligence prediction-based model in laparoscopic liver surgery for segments 7 and 8: an international multicenter study.

BACKGROUND: Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. METHODS: We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. RESULTS: Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables "resection type" and "largest tumor size" for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables "tumor location," "blood loss," "complications," and "operation time." CONCLUSION: We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.

Prevalence, knowledge, and concerns regarding the use of heated tobacco products and electronic cigarettes among young Japanese physicians.

INTRODUCTION: Heated tobacco products (HTPs) and e-cigarettes (ECs) have gained traction as alternatives for harm reduction, especially in Japan. In particular, the use of HTPs is rapidly gaining popularity among young adults in Japan, with a prevalence of 10.9% in 2020. Despite uncertainties regarding the health effects of HTPs and ECs, concerns regarding nicotine and carcinogens persist. Although physicians play a vital role in smoking cessation, they lack awareness and concerns regarding HTPs. This study aimed to assess the prevalence, knowledge, and concerns regarding HTPs and ECs among young Japanese physicians. METHODS: A cross-sectional online survey was conducted in 2021 with 529 young Japanese physicians aged 24-39 years. Parameters assessed included awareness, smoking status, knowledge of HTPs and ECs, and concerns related to HTPs. Statistical analyses were conducted to assess prevalence, knowledge, and concerns by smoking status using the chi-squared test and logistic regression. RESULTS: Most participants were aware of HTPs (89.0%) and ECs (71.3%). Young male physicians preferred HTPs, while females favored ECs. Primary sources of information included newspapers and stories (56.8%), and TV (37.4%). Non-smokers (89.0%) demonstrated limited knowledge of these products. Concerns were highest and lowest among non-smokers and HTP users, respectively, with safety concerns being the most prevalent. CONCLUSIONS: Young physicians exhibited lower smoking rates than the general population, but HTP use was prominent among young male physicians. Concerns varied based on smoking status, indicating the need to address these issues among healthcare professionals. Despite high awareness, knowledge gaps, particularly among non-smokers, highlight the importance of public health and educational campaigns to disseminate knowledge among physicians, regardless of medical specialty.

A School-Based Program for Problematic Internet Use for Adolescents in Japan.

Despite the serious influence of problematic Internet use on mental health among Japanese adolescents, no randomized clinical trials have investigated universal school-based interventions for this potential health challenge. Therefore, this study aimed to assess the efficacy of a school-based educational program. This two-armed, parallel, cluster-based randomized clinical trial included 5312 students from 13 high schools situated in a mid-sized Japanese city. The students in the intervention arm received 10 weekly standardized sessions, including a combination of information provision and interactive sessions by schoolteachers. The students in the control group followed a standard school curriculum. A generalized estimating equation model was applied to assess the primary (Korean Scale for Internet Addiction [K-scale] score) and secondary (behavioral change status according to changes in the transtheoretical model smartphone addiction score and Internet usage time) outcomes two months after intervention completion. The intention-to-treat analysis included 2597 (97.2%) and 2504 (94.9%) students in the intervention and control groups, respectively. Nevertheless, a significant discrepancy emerged regarding the behavioral change status. Therefore, this school-based program did not improve the Internet or smartphone addiction scores among Japanese adolescents. Further studies are needed to develop appropriate interventions for adolescents.

Relationship between Telework Jetlag and Perceived Psychological Distress among Japanese Hybrid Workers.

Social jetlag is associated with physical and mental health problems. With the increased popularity of telework, we investigated a specific form of social jetlag that we termed "telework jetlag". This study aimed to clarify the relationship between telework jetlag-the difference in sleep and wake-up times between in-office and telework days-and mental health problems among Japanese hybrid workers. A cross-sectional study was conducted with 1789 participants from October to December 2021 using an online-based questionnaire. Telework jetlag, defined as the difference in the midsleep point between in-office and telework days, was investigated using two groups according to telework jetlag-those lagging <1 h versus ≥1 h. We used the six-item Kessler Scale as a nonspecific psychological distress scale for the outcome. Telework jetlag was significantly associated with psychological distress, and the ≥1 h group had a higher risk (odds ratio: 1.80) of developing high psychological distress (HPD) than the <1 h group in the multivariate analysis. Since most teleworkers are forced to have a hybrid work style that mixes going to work and teleworking, telework jetlag must be addressed to maintain the health of teleworkers.

Comparison of the responses of cross-sectional web- and paper-based surveys on lifestyle behaviors of Japanese adolescents.

Objective: In Japan, paper-based surveys are currently more effective than web-based surveys. This study compared the response rates and lifestyle behaviors between paper- and web-based surveys conducted among Japanese junior and senior high schools. Methods: In total, there were 42 and 64 junior and senior high schools, respectively, for the web-based surveys and 20 and 27 junior and senior high schools, respectively, for the paper-based surveys. The questionnaire covered lifestyle behaviors (e.g., alcohol consumption, smoking, exercise, eating, and sleep status), mental health, and plans to attend college. School- and student-level response rates by survey method were assessed, and so was the effect on the reporting of each lifestyle behavior using logistic regression models. Results: The school response rates were 16.0% and 38.3% for web- and paper-based surveys, respectively. The student response rates were 88.7% and 77.2%, respectively. The web-based group had significantly more female participants and lower response rates for higher grades in senior high schools. The odds of lifetime and current alcohol consumption and poor mental health were lower, whereas those of lifetime use of conventional cigarettes, shorter sleep duration, and plans to continue attending college were higher among web-based (vs. paper-based) participants. Conclusions: The school response rate was poor in the web-based survey. However, whether the differences in lifestyle behavior are attributed to selection bias or the survey method remains unclear.

Secondhand Smoke Exposure and Smoking Prevalence Among Adolescents.

Importance: Secondhand smoke is a substantial risk factor for youth health globally, including in Japan, where tobacco control policies should be reassessed. Objective: To assess trends in the prevalence of secondhand smoke exposure among Japanese adolescents from 2008 to 2017 and to examine the association between its frequency and smoking during the study period. Design, Setting, and Participants: This study comprised a nationally representative, self-administered, school-based, cross-sectional survey focusing on tobacco and alcohol use and related factors among students in grades 7 to 12 (ages 12-18 years) in Japan. This random sampling survey used single-stage cluster sampling. Using the national school directory, junior and senior high schools throughout Japan were randomly extracted from each regional block. All students enrolled in the sampled schools were included as participants, and school-based surveys were completed in 2008, 2012, and 2017. Data analysis was performed from January 1 to March 15, 2023. Main Outcomes and Measures: Prevalence of secondhand smoke exposure among adolescents in Japan from 2008 to 2017 and changes in the association between secondhand smoke exposure frequency and prevalence of smoking were examined using multiple logistic regression analysis. Results: Data were analyzed for 95 680 adolescents in 2008 (50.7% boys), 100 050 in 2012 (51.6% boys), and 64 152 in 2017 (53.9% boys). At baseline, 42.0%, 38.5%, and 34.6% of the participants were junior high school students in 2008, 2012, and 2017, respectively. Based on the 2008 surveys, 51.0% of adolescents in grades 7 to 12 were exposed to secondhand smoke in any place (≥1 day during the past 7 days), 37.2% were exposed at home, and 36.5% were exposed in public places. In 2017, 36.3% of participants were exposed to secondhand smoke in any place, 23.8% were exposed at home, and 27.0% were exposed in public places. An association between secondhand smoke exposure frequency and prevalence of smoking was observed consistently regardless of survey year, location, or pattern of exposure (adjusted odds ratios ranged from 2.29 [95% CI, 1.81-2.91] for 1-2 days at home to 11.15 [95% CI, 8.50-14.62] for 7 days in public places). Stratified analysis by higher education intention indicated that the prevalence of smoking and secondhand smoke exposure decreased but remained higher among adolescents who did not intend to pursue higher education. The association between secondhand smoke and smoking did not differ substantially between groups. Conclusions and Relevance: In this cross-sectional study, the prevalence of secondhand smoke exposure among adolescents in Japan decreased but remained at high levels overall. There may not be a hazard-free threshold for smoking. Enhancing comprehensive tobacco control strategies is Japan's first step toward achieving smoke-free environments to protect youths. Implementation and verification of the effectiveness of smoke-free legislation should be considered.

Safety of laparoscopic liver resection for high-risk patients.

BACKGROUND/PURPOSE: To investigate the safety of laparoscopic liver resections (LLRs) for high-risk patients (HRs) with preoperative comorbidities affecting the heart, lungs, kidneys, glucose tolerance, and central nervous system. METHODS: This retrospective study included 585 patients who had undergone total hepatectomies from 2006 to 2020. Among them, 239 patients underwent LLRs, and 349 underwent open liver resections (OLRs). The safety and validity of LLRs were analyzed by comparing outcomes and preoperative records between HRs and nonhigh-risk patients (nHRs). HRs were defined as patients with any type of chronic heart disease rated New York Heart Association II or higher, chronic obstructive pulmonary disease rated stage III or higher, chronic kidney disease rated stage III or higher, insulin-dependent diabetes mellitus, or cerebrovascular disease with neurological sequelae. RESULTS: A total of 117 LLRs (49.0%) were performed in HRs, and there were more patients with ASA class III or higher than nHRs. Complications of Clavien-Dindo classification grade 3b or higher were not observed in HRs and in only one nHR. Furthermore, no postoperative exacerbations of the five HRs factors were observed in either group. CONCLUSIONS: Rigorous assessment of surgical indications and perioperative management can promote safe LLRs, even in HRs with comorbidities.

Association and dose-response relationship between exposure to alcohol advertising media and current drinking: a nationwide cross-sectional study of Japanese adolescents.

BACKGROUND: Underage drinking is a public health concern. However, few studies have examined the association between alcoholic beverage advertising and underage drinking, particularly in countries with low underage drinking rates, such as Japan. Therefore, we aimed to investigate the relationship between exposure to advertising in various media and alcohol drinking among Japanese adolescents. METHODS: We conducted a cross-sectional study involving 15,683 adolescents (51% girls) using data from a nationwide lifestyle survey in 2021 among junior and senior high schools across Japan. Media types were websites, stores, and public transportation. We defined current drinking as alcohol consumption of ≥1 day in the 30 days preceding the survey. Multivariable logistic regression was used to examine the association between exposure to alcohol advertisements and current drinking, adjusting for sex, grades, school area, lifestyle (bedtime and having fun at school), and addictive behaviors (smoking status and parents' alcohol consumption). RESULTS: The prevalence of current drinking was 2.2% (2.3% of boys and 2.0% of girls). Students who were exposed to any alcohol advertising media had higher odds of current drinking compared with those who were not (odds ratio, 1.48; 95% confidence interval [CI], 1.18-1.87). Students who were exposed to web, in-store, and public transportation advertisements had odds ratios of 1.44 (95% CI, 1.14-1.81), 1.62 (1.28-2.05), and 1.45 (1.06-1.98) of current drinking, respectively, compared with those who were not. The association of exposure to alcohol advertising media with the prevalence of current drinking was similar among boys and girls (all p for sex interaction >0.1), except for that of exposure to web advertisements; its association with current drinking was more pronounced in girls (p for sex interaction = 0.046). Exposure to a larger cumulative number of different alcohol advertising media was independently associated with a higher prevalence of current drinking among all students, boys, and girls (p-values for trend <0.001, 0.031, and <0.001, respectively; p for sex interaction = 0.085). CONCLUSIONS: We found an association with a dose-response relationship between exposure to alcohol advertisements and current drinking among adolescents in junior and senior high schools across Japan. Our findings highlight the need for further advertising regulations to prevent underage drinking.

Lymphadenitis caused by Purpureocillium lilacinum in a patient with CARD9 deficiency.

We hereby make the first report of a case of mycosis caused by Purpureocillium lilacinum in CARD9 deficiency. A 40-year-old woman complained of lymph node swellings in the left cervical area. She also had chronic mucocutaneous candidiasis (CMC), and was found to have CARD9 deficiency. Lymphadenitis by P. lilacinum was confirmed. The diagnosis was difficult, as culturing the biopsy specimen at a cautiously selected temperature (25 °C) and genetic analysis were both required. Oral administration of voriconazole improved her lymphadenopathy.

Impact of chronotype, insomnia symptoms, sleep duration, and electronic devices on nonrestorative sleep and daytime sleepiness among Japanese adolescents.

OBJECTIVES: Nonrestorative sleep (NRS) and excessive daytime sleepiness (EDS) are important indicators of daytime dysfunction. Electronic media use before bedtime greatly affects adolescent sleep quality. However, few studies have examined factors associated with these symptoms. Therefore, we aimed to investigate the impact of chronotype, electronic device use before bedtime, and insomnia symptoms on NRS and EDS in Japanese adolescents. METHODS: A web-based cross-sectional survey of 2067 adolescents was conducted in 2022 to mainly assess sleep-related issues (sleep duration, chronotype, insomnia symptoms, NRS, and EDS), time spent using electronic devices, physical activity, and mental health. RESULTS: We analyzed data of 1880 adolescents (age, 16.4 ± 0.8 years; males, 56.7%). NRS and EDS prevalence rates were 54.9% and 39.4%, respectively. In multivariate analysis, evening chronotype [odds ratio (OR): 2.14, 95% confidence interval (CI): 1.58-2.89], difficulty initiating sleep (OR: 1.94, 95% CI: 1.43-2.64), <5 h sleep (OR: 1.77, 95% CI: 1.24-2.54), 5-6 h sleep (OR: 1.52, 95% CI: 1.20-1.93), and using electronic devices just before bedtime (OR: 1.48, 95% CI: 1.08-2.04) were associated with NRS. Evening chronotype (OR: 1.40, 95% CI: 1.07-1.82), early morning awakening (OR: 1.60, 95% CI: 1.02-2.50), using electronic devices just before bedtime (OR: 2.08, 95% CI: 1.48-2.93), and using electronic devices 30 min before bedtime (OR: 1.57, 95% CI: 1.07-2.29) were associated with EDS. CONCLUSION: Chronotype may be an important factor influencing NRS and EDS. Discontinuing electronic device use at least 30 min before bedtime could benefit affected adolescents.

The Outcome of Conversion to Hand-Assisted Laparoscopic Surgery in Laparoscopic Liver Resection.

BACKGROUND: Hand-assisted laparoscopic surgery (HALS) is known as a useful option. However, the outcome and predictor of conversion to HALS in laparoscopic liver resection (LLR) are unclear. METHODS: Data from consecutive patients who planned pure LLR between 2011 and 2020 were retrospectively reviewed. Univariate and multivariate analyses were performed and compared pure LLR, HALS, and converted open liver resection (OLR). RESULTS: Among the 169 LLRs, conversion to HALS was performed in 19 (11.2%) and conversion to OLR in 16 (9.5%). The most frequent reasons for conversion to HALS were failure to progress (11 cases). Subsequently, bleeding (3 cases), severe adhesion (2 cases), and oncological factors (2 cases) were the reasons. In the multivariable analysis, the tumor located in segments 7 or 8 (p = 0.002) was evaluated as a predictor of conversion to HALS. Pure LLR and HALS were associated with less blood loss than conversion to OLR (p = 0.005 and p = 0.014, respectively). However, there was no significant difference in operation time, hospital stay, or severe complications. CONCLUSIONS: The predictor of conversion to HALS was a tumor located in segments 7 or 8. The outcome of conversion to HALS was not inferior to pure LLR in terms of bleeding, operation time, hospital stay, or severe complication.

The effect of nonrestorative sleep on incident hypertension 1-2 years later among middle-aged Hispanics/Latinos.

BACKGROUND: Insomnia is known to be a major risk factor for incident hypertension. Nonrestorative sleep (NRS), which refers to insufficiently rested sleep, has reported to associate with various diseases. This study aimed to investigate the longitudinal association between insomnia-related symptoms including NRS and incident hypertension 1-2 years later by age group (young, 18-39 years and middle-age, 40-64 years) using existing cohort data involving Hispanics/Latinos. METHODS: This study included 1100 subjects who had participated in both the Hispanic Community Health Study/Study of Latinos and its follow-up study, the Sueño Ancillary Study, and met additional eligibility criteria. Incident hypertension was assessed by self-reported history and/or the use of antihypertensives. The Women's Health Initiative Insomnia Rating Scale (WHIIRS) was used to evaluate insomnia-related symptoms (difficulty initiating sleep, difficulty maintaining sleep, early morning awakening, difficulty returning to sleep, and NRS). Logistic regression analyses were conducted to assess the degree to which insomnia-related symptoms at baseline predicted incident hypertension. RESULTS: Among the participants (64% middle-aged, 36% young adults), 140 (12.7%) developed hypertension during the follow-up period. Among the sleep-related symptoms, only NRS predicted incident hypertension after adjusting for sociodemographic factors and physical condition (odds ratio: 1.88, 95% confidence interval: 1.10-3.21, p = 0.022) in middle-aged adults. None of the insomnia-related symptoms were associated with incident hypertension in the young adults. No association was found between WHIIRS-defined insomnia (total score ≥ 9) and incident hypertension in middle-aged adults or young adults. CONCLUSION: The present findings suggest the importance of focusing on NRS to help prevent the development of hypertension in middle-aged adults.

Optimal telework frequency in terms of sleep and labor productivity depends on the workers' psychological distress: A cross-sectional study in Tokyo, Japan.

OBJECTIVES: This study aimed to determine that workers' sleep and labor productivity differ with the telework frequency and that the optimal telework frequency depends on workers' psychological distress. METHODS: A cross-sectional study using an online-based questionnaire was conducted with 2,971 workers employed by Japanese companies from October to December 2021. We used the 6-item Kessler Scale, K6, as a nonspecific psychological distress scale to screen mental health conditions. A score of ≤ 4 was defined as low psychological distress (LPD), and a score of ≥ 5 was defined as high psychological distress (HPD). We used the Athens Insomnia Scale (AIS) as a measure of sleep quality. The Utrecht Work Engagement (UWES) and Work Functioning Impairment (WFun) scales were used as measures of labor productivity. Series of analysis of covariance (ANCOVA) was used for the data analysis. RESULTS: The analysis included 2,013 participants (1,390 men and 623 women; mean age 43.2 years, standard deviation 11.3). Multiple comparison tests showed that among the participants categorized HPD (HPD type), the AIS estimates were lowest in the 1-2 d/wk group, with significant differences between the 0-3 d/m and ≥ 5 d/wk groups. UWES estimates were lowest in the 3-4 d/wk group with significant differences between the participants categorized LPD (LPD type) and HPD type, while no significant differences were observed among the LPD type. The WFun estimates among the LPD type decreased significantly with increasing telework frequency, while no significant differences were observed among the HPD type. CONCLUSIONS: The optimal telework frequency for sleep and labor productivity may depend on the workers' psychological distress. The finding of this study could make a great contribution to occupational health activities and health promotion for teleworkers, which is necessary to make teleworking a sustainable work style.

[Surgical Resection as Local Therapy for Sister Mary Joseph's Nodule Due to Pancreatic Tail Cancer].

We experienced a case of resection of a metastatic umbilical tumor(Sister Mary Joseph's nodule: SMJN)derived from a pancreatic tail carcinoma. The patient was a 70-year-old woman. She visited her previous doctor with a chief complaint of lower abdominal pain and came to our hospital due to suspicion of pancreatic tail cancer. She was found to have metastases to multiple organs which was unresectable by surgery. After chemotherapy up to the second-line of treatment, she was diagnosed to have progressive disease. The decision was made to provide the best supportive care for the patient. Thereafter, the patient developed SMJN. She had hemorrhage from the tumor accompanied by body movement, and her activity of daily living became impaired. She had difficulty controlling the bleeding despite repeated hemostatic treatment at the outpatient clinic and at her home. However, she required frequent blood transfusions for her severe anemia. Therefore, we performed a resection of the SMJN to control bleeding and to relieve her symptoms. She had a good postoperative course and was discharged on the fifth postoperative day. Due to deterioration of her general condition, she expired on the 59th day after surgery. However, the patient was able to live at home without bleeding or pain by the umbilical tumor. The local resection was considered to be useful as a palliative surgical treatment for SMJN.

Experience-Related Factors in the Success of Beginner Endoscopic Ultrasound-Guided Biliary Drainage: A Multicenter Study.

Endoscopic ultrasound-guided biliary drainage (EUS-BD) has become comparable to endoscopic retrograde cholangiopancreatography and is now considered a first-line intervention for certain biliary obstructions. Although analysis of experience-related factors may help achieve better outcomes and contribute to its wider adoption, no concrete evidence exists regarding the required operator or institutional experience levels. This study aimed to analyze experience-related factors at beginner multicenters. Patients who underwent EUS-BD using self-expandable metal stents and/or dedicated plastic stents during the study period (up to the first 25 cases since introducing the technique) were retrospectively enrolled from seven beginner institutions and operators. Overall, 90 successful (technical success without early adverse events) and 22 failed (technical failure and/or early adverse events) cases were compared. EUS-BD-related procedures conducted at the time of applicable EUS-BD by each institution/operator were evaluated. The number of institution-conducted EUS-BD procedures (≥7) and operator-conducted EUS screenings (≥436), EUS-guided fine-needle aspirations (FNA) (≥93), and EUS-guided drainages (≥13) significantly influenced improved EUS-BD outcomes (p = 0.022, odds ratio [OR], 3.0; p = 0.022, OR, 3.0; p = 0.022, OR, 3.0; and p = 0.028, OR, 2.9, respectively). Our threshold values, which significantly divided successful and failed cases, were assessed using receiver operating characteristic curve analysis and may provide useful approximate indications for successful EUS-BD.

High-level production of 2-pyrone-4,6-dicarboxylic acid from vanillic acid as a lignin-related aromatic compound by metabolically engineered fermentation to realize industrial valorization processes of lignin.

2-Pyrone-4,6-dicarboxylic acid (PDC) is a valuable building block molecule produced from lignin-derived aromatic compounds by biological funneling. This study aimed to design a fermentation process for producing PDC from vanillic acid, which could be applied at an industrial production. Metabolomic analysis revealed that a high primary metabolic activity within cells was required to improve the production efficiency. Moreover, a medium with ammonium salts and no alkali metals was advantageous because it suppressed the formation of PDC-metal complexes. Resulting optimized process yielded the highest PDC titer and productivity ever reported: 99.9 g/L and 1.69 g/L/h, respectively. Per batch, 190 g of PDC was produced per liter of initial culture media, and the final liquid volume was 1.9 L. This study demonstrates the design of fermentation processes for the advanced industrial utilization of lignin by biological funneling.

Nonrestorative sleep is a risk factor for metabolic syndrome in the general Japanese population.

BACKGROUND: This longitudinal study aimed to investigate the effects of nonrestorative sleep on developing metabolic syndrome (MetS) and related diseases in a general Japanese middle-aged population. METHODS: Overall, 83,224 adults without MetS (mean age: 51.5 ± 3.5 years) from the Health Insurance Association in Japan were followed up for a maximum of 8 years between 2011 and 2019. The Cox proportional hazard method was used to determine whether nonrestorative sleep, assessed using a single-item question, was significantly associated with the respective development of MetS, obesity, hypertension, diabetes, and dyslipidemia. The MetS criteria were adopted by the Examination Committee for Criteria of Metabolic Syndrome in Japan. RESULTS: The mean follow-up duration was 6.0 years. The incidence rate of MetS was 50.1 person-years/1,000 during the study period. Data suggested that nonrestorative sleep was associated with MetS (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.08-1.16) and other disorders, such as obesity (HR: 1.07, 95% CI: 1.02-1.12), hypertension (HR: 1.07, 95% CI: 1.04-1.11), and diabetes (HR: 1.07, 95% CI: 1.01-1.12) but not with dyslipidemia (HR: 1.00, 95% CI: 0.97-1.03). CONCLUSIONS: Nonrestorative sleep is associated with the development of MetS and many of its core components in the middle-aged Japanese population. Therefore, assessing nonrestorative sleep may help identify individuals at a risk of MetS development.