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Cervical cancer remains among the most common cancers in women worldwide and can be prevented by vaccination. The Ministry of Health, Labour and Welfare of Japan suspended active recommendation of regular human papillomavirus (HPV) vaccines in 2013 because of various symptoms including chronic pain and motor impairment. This nationwide case‐control study from April 2013 to March 2017 targeted women aged 20‐24 years old at cervical screening. We compared HPV vaccination exposure between those with abnormal and normal cytology. Abnormal cytology was classified based on the results of histological test and we calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 – OR) × 100. A total of 2483 cases and 12 296 controls (one‐to‐five matching) were eligible in 31 municipalities in Japan. The distribution of histological abnormalities among cases was 797 CIN1 (including dysplasia) (32.1%), 165 CIN2 (6.7%), 44 CIN3 (1.8%), and eight squamous cell carcinoma (SCC) (0.3%). The OR of HPV vaccination compared with no vaccination for abnormal cytology, CIN1+, CIN2+, and CIN3+ versus controls was 0.42 (95% CI, 0.34‐0.50), 0.42 (95% CI, 0.31‐0.58), 0.25 (95% CI, 0.12‐0.54), and 0.19 (95% CI, 0.03‐1.15), respectively, equating to a vaccine effectiveness of 58.5%, 57.9%, 74.8%, and 80.9%, respectively. Eight patients had SCC, none was vaccinated. This nationwide case‐control study in Japan demonstrated a substantial risk reduction in abnormal cytology and CIN among women who did versus those who did not receive HPV vaccination. This nationwide case‐control study with official vaccination records in Japan demonstrated a substantial risk reduction in abnormal cytology and CIN among women who did versus those who did not receive HPV vaccination.

Background: Since June 2013, Japan has suspended proactive recommendation of human papillomavirus (HPV) vaccination due to self-reported diverse symptoms, including pain and motor dysfunction, as possible serious adverse events following immunization. Although these symptoms may be seen in adolescents without HPV vaccination, their frequency, taking into account disease severity, has not been examined.Methods: A two-stage, descriptive, nationwide epidemiological survey was conducted in 2016, with a 6-month target period from July 1 to December 31, 2015, to estimate the prevalence and incidence of diverse symptoms among Japanese adolescents without HPV vaccination. Participants were 11,037 medical departments in hospitals selected nationwide by stratified random sampling. Eligible patients had to satisfy four criteria: (1) aged 12–18 years upon visiting hospital; (2) having at least one of four symptoms/disorders (pain or sensory dysfunction, motor dysfunction, autonomic dysfunction, or cognitive impairment); (3) symptoms/disorders persisting for at least 3 months; and (4) both criteria (2) and (3) influence attendance at school or work. We then extracted data of patients with diverse symptoms similar to those after HPV vaccination while considering opinions of doctors in charge.Results: Estimated 6-month period prevalence of diverse symptoms among girls aged 12–18 years without HPV vaccination was 20.2 per 100,000. Annual incidence was estimated to be 7.3 per 100,000.Conclusion: Adolescent Japanese girls without HPV vaccination also visited hospitals with diverse symptoms similar to those following HPV vaccination. Our findings predict the medical demands for coincident diverse symptoms, which are temporally associated with but not caused by HPV vaccination of Japanese adolescents.

Occupational asbestos exposure occurs in many workplaces and is a well‐known cause of mesothelioma and lung cancer. However, the association between nonoccupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause‐specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos‐related diseases. The study population consisted of 143 929 residents in Amagasaki City before 1975 until 2002, aged 40 years or older on January 1, 2002. Follow‐up was carried out from 2002 to 2015. Standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated by sex, using the mortality rate of the Japanese population as reference. A total of 38 546 deaths (including 303 from mesothelioma and 2683 from lung cancer) were observed. The SMRs in the long‐term residents’ cohort were as follows: death due to all causes, 1.12 (95% CI, 1.10‐1.13) in men and 1.07 (95% CI, 1.06‐1.09) in women; lung cancer, 1.28 (95% CI, 1.23‐1.34) in men and 1.23 (95% CI, 1.14‐1.32) in women; and mesothelioma, 6.75 (95% CI, 5.83‐7.78) in men and 14.99 (95% CI, 12.34‐18.06) in women. These SMRs were significantly higher than expected. The increased SMR of mesothelioma suggests the impact of occupational asbestos exposure among men and nonoccupational asbestos exposure among women in the long‐term residents’ cohort. In addition, the high level of excess mortality from mesothelioma has persisted, despite the mixture of crocidolite and chrysotile no longer being used for three or four decades. Our paper provides an investigation on the cause‐specific mortality among the residents in a unique urban area where asbestos‐related factories were concentrated in Japan. The excess mortality due to mesothelioma suggests the impact of occupational asbestos exposure in men and nonoccupational asbestos exposure in women in the cohort.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that starts in early childhood and has a comprehensive impact on psychosocial activity and education as well as general health across the lifespan. Despite its prevalence, the current diagnostic criteria for ADHD are debated. Saccadic eye movements are easy to quantify and may be a quantitative biomarker for a wide variety of neurological and psychiatric disorders, including ADHD. The goal of this study was to examine whether children with ADHD exhibit abnormalities during a visually guided pro-saccadic eye-movement and to clarify the neurophysiological mechanisms associated with their behavioral impairments. Thirty-seven children with ADHD (aged 5-11 years) and 88 typically developing (TD) children (aged 5-11 years) were asked to perform a simple saccadic eye-movement task in which step and gap conditions were randomly interleaved. We evaluated the gap effect, which is the difference in the reaction time between the two conditions. Children with ADHD had a significantly longer reaction time than TD children (p < 0.01) and the gap effect was markedly attenuated (p < 0.01). These results suggest that the measurement of saccadic eye movements may provide a novel method for evaluating the behavioral symptoms and clinical features of ADHD, and that the gap effect is a potential biomarker for the diagnosis of ADHD in early childhood.

Background: A high body mass index (BMI) has been proposed as an important risk factor for pancreatic cancer. However, this association of BMI with pancreatic cancer risk has not been confirmed in Asian populations. Methods: We evaluated the association between BMI (either at baseline or during early adulthood) and pancreatic cancer risk by conducting a pooled analysis of nine population-based prospective cohort studies in Japan with more than 340,000 subjects. Summary hazard ratios (HRs) were estimated by pooling study-specific HRs for unified BMI categories with a random-effects model. Results: Among Japanese men, being obese at baseline was associated with a higher risk of pancreatic cancer incidence (≥30 kg/m2 compared with 23 to <25 kg/m2, adjusted HR 1.71; 95% confidence interval [CI], 1.03–2.86). A J-shaped association between BMI during early adulthood and pancreatic cancer incidence was seen in men. In contrast, we observed no clear association among women, although there may be a positive linear association between BMI at baseline and the risk of pancreatic cancer (per 1 kg/m2, adjusted HR 1.02; 95% CI, 1.00–1.05). Conclusions: Pooling of data from cohort studies with a considerable number of Japanese subjects revealed a significant positive association between obesity and pancreatic cancer risk among men. This information indicates that strategies that effectively prevent obesity among men might lead to a reduced burden of pancreatic cancer, especially in Asian populations.

A causal relationship between mesothelioma and occupational asbestos exposure is well known, while some studies have shown a relationship to non‐occupational exposures. The aim of this study was to quantify the risk of mesothelioma death associated with neighborhood asbestos exposure due to a large‐scale asbestos‐cement (AC) plant in Amagasaki, Japan, adjusting properly risk factors including occupational exposures. We conducted a nested case‐control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with the neighborhood exposure were estimated by a conditional logistic‐regression model. For quantitative assessments for neighborhood exposure, we adopted cumulative indices for individuals' residential histories at each residence‐specific asbestos concentration multiplied by the duration during the potential exposure period of 1957–1975 (crocidolite). We observed an increasing, dose‐dependent risk of mesothelioma death associated with neighborhood exposure, demonstrating that ORs in the highest quintile category were 21.4 (95% confidence interval [CI] 5.8–79.2) for all, 23.7 (95% CI 3.8–147.2) for males, and 26.0 (95% CI 2.8–237.5) for females compared to the lowest quintile, respectively. A quantitative assessment for risk of mesothelioma deaths, adjusting for occupational and non‐occupational exposures separately, showed a dose‐dependent association with neighborhood exposure and no substantial gender differences in magnitude. We adopted cumulative indices that considered residence‐specific asbestos (crocidolite) concentrations and durations exposed during the period 1957–1975 for evaluation of neighborhood exposure. By adjusting properly for occupational and other considerable exposures, we demonstrated quantitative risk assessments of mesothelioma deaths dose‐dependently associated with neighborhood exposure due to a large‐scale asbestos cement plant in Amagasaki City, Japan. Our findings also showed there was no substantial gender difference in the magnitude of the risk in relation to neighborhood asbestos exposure.

This retrospective study aimed to develop and validate a deep learning model for the classification of coronavirus disease-2019 (COVID-19) pneumonia, non-COVID-19 pneumonia, and the healthy using chest X-ray (CXR) images. One private and two public datasets of CXR images were included. The private dataset included CXR from six hospitals. A total of 14,258 and 11,253 CXR images were included in the 2 public datasets and 455 in the private dataset. A deep learning model based on EfficientNet with noisy student was constructed using the three datasets. The test set of 150 CXR images in the private dataset were evaluated by the deep learning model and six radiologists. Three-category classification accuracy and class-wise area under the curve (AUC) for each of the COVID-19 pneumonia, non-COVID-19 pneumonia, and healthy were calculated. Consensus of the six radiologists was used for calculating class-wise AUC. The three-category classification accuracy of our model was 0.8667, and those of the six radiologists ranged from 0.5667 to 0.7733. For our model and the consensus of the six radiologists, the class-wise AUC of the healthy, non-COVID-19 pneumonia, and COVID-19 pneumonia were 0.9912, 0.9492, and 0.9752 and 0.9656, 0.8654, and 0.8740, respectively. Difference of the class-wise AUC between our model and the consensus of the six radiologists was statistically significant for COVID-19 pneumonia ( p value = 0.001334). Thus, an accurate model of deep learning for the three-category classification could be constructed; the diagnostic performance of our model was significantly better than that of the consensus interpretation by the six radiologists for COVID-19 pneumonia.

Aim Timely use of automated external defibrillators by lay rescuers significantly improves the chances of survival in out‐of‐hospital cardiac arrest cases. We aimed to identify the factors influencing whether lay rescuers bring automated external defibrillators to the scene of nontraumatic out‐of‐hospital cardiac arrests in schoolchildren in Japan. Methods Data on out‐of‐hospital cardiac arrests among schoolchildren from April 2008 to December 2021 were obtained from the database of the Stop and Prevent cardIac aRrest, Injury, and Trauma in Schools study. A multivariate Modified Poisson regression analysis was performed to evaluate the factors influencing whether a lay rescuer brought an automated external defibrillator to the scene of out‐of‐hospital cardiac arrest and the year‐by‐year changes in automated external defibrillator delivery for each factor were assessed. Results Of the 333 nontraumatic out‐of‐hospital cardiac arrests across the entire study period, lay rescuers brought automated external defibrillators in 85.3% of cases. Female patients and incidents occurring during non‐sports activities had lower proportions of automated external defibrillator delivery. Significant year‐by‐year improvements in automated external defibrillator delivery were observed, with the overall proportion increasing from 73.7% in 2008–2010 to 93.3% in 2020–2021. However, the trend was less pronounced for female students, non‐sports activities, and incidents occurring in classrooms/other locations than their counterparts. Conclusions AED delivery to the scene of OHCA in schools has improved overall, with the proportion increasing from 73.7% in 2008–2010 to 93.3% in 2020–2021. However, there is still room for improvement, particularly in female patients, and incidents during non‐sports activities. We investigated factors affecting whether lay rescuers bring AEDs to nontraumatic OHCAs in Japanese schools. From 2008 to 2021, overall AED delivery rates improved significantly, but incidents involving female students and those occurring during non‐sport activities still show lower AED delivery rates. Further efforts are necessary to address these disparities.

Chronic enteropathy associated with SLCO2A1 gene (CEAS) is caused by loss-of-function mutations in SLCO2A1 , which encodes a prostaglandin (PG) transporter. In this study, we report a sibling case of CEAS with a novel pathogenic variant of the SLCO2A1 gene. Compound heterozygous variants in SLCO2A1 were identified in an 8-year-old boy and 12-year-old girl, and multiple chronic nonspecific ulcers were observed in the patients using capsule endoscopy. The splice site mutation (c.940 + 1G>A) of the paternal allele was previously reported to be pathogenic, whereas the missense variant (c.1688T>C) of the maternal allele was novel and had not yet been reported. The affected residue (p.Leu563Pro) is located in the 11th transmembrane domain (helix 11) of SLCO2A1. Because SLCO2A1 mediates the uptake and clearance of PGs, the urinary PG metabolites were measured by liquid chromatography coupled to tandem mass spectrometry. The urinary tetranor-prostaglandin E metabolite levels in the patients were significantly higher than those in unaffected individuals. We established cell lines with doxycycline-inducible expression of wild type SLCO2A1 (WT-SLCO2A1) and the L563P mutant. Immunofluorescence staining showed that WT-SLCO2A1 and the L563P mutant were dominantly expressed on the plasma membranes of these cells. Cells expressing WT-SLCO2A1 exhibited time- and dose-dependent uptake of PGE 2 , while the mutant did not show any uptake activity. Residue L563 is very close to the putative substrate-binding site in SLCO2A1, R561 in helix 11. However, in a molecular model of SLCO2A1, the side chain of L563 projected outside of helix 11, indicating that L563 is likely not directly involved in substrate binding. Instead, the substitution of Pro may twist the helix and impair the transporter function. In summary, we identified a novel pathogenic variant of SLCO2A1 that caused loss-of-function and induced CEAS.

Red meat and processed meat have been suggested to increase risk of colorectal cancer (CRC), especially colon cancer. However, it remains unclear whether these associations differ according to meat subtypes or colon subsites. The present study addressed this issue by undertaking a pooled analysis of large population‐based cohort studies in Japan: 5 studies comprising 232 403 participants (5694 CRC cases) for analysis based on frequency of meat intake, and 2 studies comprising 123 635 participants (3550 CRC cases) for analysis based on intake quantity. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model and then pooled using the random effect model. Comparing the highest vs lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20; 95% CI, 1.01‐1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30; 95% CI, 1.05‐1.61). Frequent intake of pork was associated with an increased risk of distal colon cancer in women (pooled HR 1.44; 95% CI, 1.10‐1.87) for “3 times/wk or more” vs “less than 1 time/wk”. Frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39; 95% CI, 0.97‐2.00; P trend = .04) for “almost every day” vs “less than 1 time/wk”. No association was observed for chicken consumption. The present findings support that intake of beef, pork (women only), and processed red meat (women only) might be associated with a higher risk of colon (distal colon) cancer in Japanese. As shown in figure A and figure B, comparing the highest versus lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20, 95% CI 1.01‐1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30, 95% CI 1.05‐1.61). Figure C shows that frequent intake of pork was associated with an increased risk of DCC in women (pooled HR 1.44, 95% CI 1.10‐1.87) for “3 times/week or more” versus “<1time/week”. Figure D shows that frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39, 95% CI 0.97‐2.00; p‐trend=0.04) for “almost every day” versus “<1 time/week”.