Background/Objectives: Smoking is an established cofactor for cervical carcinogenesis, but evidence on how Smoking Pattern Changes around cohort entry relate to risk in Japan is limited. We quantified cervical cancer risk by baseline smoking status and by changes between two routine health checkups in a nationwide cohort. Methods: We used the Japan Medical Data Center claims–checkup database between January 2005 and July 2022. Women with ≥2 pre-index checkups were included; the index date was the second checkup. Self-reported smoking at each visit defined never, former (quit), new (initiated), and current (persistent) smokers; checkup pairs >36 months apart were excluded. Incident cervical cancer required ICD-10 C53 plus cancer-directed treatment (surgery, radiotherapy, or systemic antineoplastic therapy). Multivariable Cox models estimated hazard ratios (HRs) with 95% CIs, adjusting for age, BMI, alcohol, exercise, hypertension, diabetes, cerebrovascular and cardiovascular disease, and cholangitis. Results: Among 1,330,797 women, incidence rates (per 100,000 person-years) were 151.4 in never smokers and 244.9 in ever smokers. Ever versus never smoking was associated with higher risk (HR 1.53, 95% CI 1.43–1.62). A graded risk was observed across Smoking Pattern Change categories versus never: former HR 1.44 (1.15–1.79), new HR 1.51 (1.20–1.90), current HR 1.54 (1.44–1.64). By age, HRs were 1.58 (1.47–1.70) for <50 years and 1.35 (1.17–1.55) for 50–64 years; ≥65 years was not statistically significant (HR 0.69, 0.30–1.59). Conclusions: Smoking was associated with substantially higher cervical cancer risk, with a clear risk gradient from former to new to current smoking. The rapid elevation in new smokers and residual risk after quitting support integrating proactive cessation and initiation prevention into risk-stratified screening and routine health-check programs in Japan.

Background: Low high-density lipoprotein cholesterol (HDL-C) is an established marker of cardiovascular risk. However, HDL-C levels may change over time in relation to metabolic status, lifestyle factors, and medication use, and the cardiovascular implications of longitudinal HDL-C changes remain incompletely understood. Methods: We conducted a retrospective cohort study using the JMDC Claims Database, including 3,387,924 adults who underwent at least two health checkups between 2005 and 2021. Participants were categorized into four groups based on HDL-C changes between two time points: persistently low, low to normal, normal to low, and persistently normal. The primary outcome was incident composite cardiovascular disease (CVD), including myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Cox proportional hazards models were used to estimate hazard ratios (HRs) with adjustment for demographic and clinical covariates. Results: During a mean follow-up of 4.3 years, persistently low HDL-C was associated with the highest risk of composite CVD compared with persistently normal HDL-C (HR 1.15, 95% CI 1.12–1.19). Both Low-to-Normal and Normal-to-Low groups also showed elevated risks (HR 1.10, 95% CI 1.06–1.14; HR 1.14, 95% CI 1.10–1.19, respectively). The strongest association was observed for myocardial infarction, whereas the association with stroke was modest and less consistent after full adjustment. Conclusions: Longitudinal changes in HDL-C were associated with cardiovascular risk after adjustment for cardiometabolic factors and medication use. Persistently low HDL-C conferred the greatest risk, and serial HDL-C patterns may provide additional information for cardiovascular risk assessment beyond a single baseline measurement.

Purpose: Fluid intelligence (FI), a core cognitive function involved in reasoning and problem-solving, has been linked to psychiatric outcomes in observational studies. However, causal inferences remain challenging due to confounding and reverse causation. This study aimed to investigate the causal effects of FI on 10 major psychiatric disorders using Mendelian randomization (MR).Methods: We performed a phenome-wide association study-based two-sample MR analysis to evaluate the effects of genetically proxied FI on 10 psychiatric disorders. Genome-wide association study summary statistics were obtained from large-scale European cohort studies. The inverse-variance-weighted method served as the primary analytical method, and complementary sensitivity analyses were conducted to assess pleiotropy and heterogeneity.Results: Higher FI was causally associated with a reduced risk of attention-deficit/hyperactivity disorder (ADHD) (odds ratio [OR], 0.72; P< 0.001), schizophrenia (OR, 0.69; P= 0.016), and post-traumatic stress disorder (PTSD) (OR, 0.93; P= 0.006). In contrast, FI was positively associated with an increased risk of autism spectrum disorder (ASD; OR, 1.43; P < 0.001) and anorexia nervosa (OR, 1.39; P= 0.005). No significant associations were observed for major depressive disorder, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, or postpartum depression. Sensitivity analyses supported the robustness of these findings, with no evidence of directional pleiotropy or undue influence of individual single-nucleotide polymorphisms.Conclusion: This study provides genetic evidence that higher FI exerts divergent causal effects across psychiatric disorders, protective in externalizing and stress-related conditions (ADHD, PTSD, and schizophrenia) but associated with an increased risk of neurodevelopmental and internalizing conditions (ASD and anorexia nervosa). These findings highlight the need for a nuanced understanding of cognitive capacity in psychiatric vulnerability and guide preventive strategies tailored to disorder-specific cognitive profiles.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome integrates metabolic, kidney, and cardiovascular abnormalities into a five-stage framework, but stroke-specific evidence across the full CKM spectrum remains limited in East Asian populations.Methods: We conducted retrospective cohort studies using Korean National Health Insurance Service and Japanese JMDC data. Participants were classified into CKM stages 0–4 and followed for total, ischemic, and hemorrhagic stroke. Cox models were fitted independently in each cohort with multivariable adjustment.FindingsWe included 4,524,279 participants in Korea and 767,913 in Japan. In Korea, adjusted hazard ratios (HRs) for total stroke versus stage 0 were 1.19 (95% CI 1.15–1.22), 1.41 (1.38–1.46), 1.65 (1.59–1.71), and 1.73 (1.67–1.78) for stages 1–4. In Japan, stage 1 was not associated with total stroke (HR 1.05, 0.86–1.28), whereas stages 2–4 were associated with higher risk (2.47, 2.13–2.86; 4.26, 3.21–5.66; 3.77, 3.08–4.61). Similar patterns were observed for ischemic and hemorrhagic stroke.Interpretation: Across two independent East Asian populations, advanced CKM stages were associated with higher incident stroke risk. Stage 2 was the earliest stage at which increased risk was consistently evident in both countries, supporting the regional applicability of CKM staging while highlighting population-specific differences at earlier stages.Funding: Sungkyunkwan University; BK21 FOUR program, Ministry of Education, Republic of Korea; National Research Foundation of Korea; and Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2025-02309552).

Purpose: Osteosarcopenia, characterized by the concurrent deterioration of bone and muscle, is increasingly recognized as a major geriatric syndrome. However, its causal role in degenerative spinal disorders remains unclear owing to confounding and reverse causation in observational studies.Methods: Two-sample Mendelian randomization (MR) was performed using appendicular lean mass (ALM), hand grip strength (HGS), walking pace (WP), and total bone mineral density (BMD) as variables. The outcomes included intervertebral disc disorder (IVDD), spinal stenosis, and spondylosis. Bidirectional MR analysis was also conducted. Genome-wide association study data were obtained from the UK Biobank, Million Veteran Program and Genetic Investigation of Anthropometric Traits (GIANT) consortium. Inverse-variance weighted was the main method for evaluating the causal relationship. Linkage disequilibrium score regression (LDSC) was used to assess genetic correlations. Multivariable MR incorporating body mass index was performed to identify the direct and indirect pathways.Results: LDSC revealed significant genetic correlations between ALM and total BMD and degenerative spinal disorders, and WP showed consistent negative genetic correlations across outcomes. In univariable MR, genetically predicted higher ALM was associated with increased risks of IVDD, spinal stenosis, and spondylosis, whereas faster WP and higher total BMD were protective. HGS showed no robust association in the primary MR analyses, although a modest protective signal for spondylosis appeared only after outlier correction. Reverse-direction MR provided limited evidence of causality.Conclusion: Osteosarcopenia-related traits exhibit heterogeneous causal relationships with degenerative spinal disorders. Muscle mass (ALM) was positively associated with the risk of spinal disorders, whereas mobility (WP) and bone density (BMD) were protective. Body size-related pathways likely contribute to these relationships, and method-dependent findings—particularly for HGS and reverse-direction analyses—should be interpreted cautiously.

Habtamu Milkias Wolde, Sunyeup Kim, Minyoung Kim, Ali Raza, Yeonsun Yu, Kihoon Moon, Sunhwa Kim, Yeongjae Kim, Beom Seok Jeong, Youngoh Bae, Seung Won Lee. KOBRA Reports 2026;2:. https://doi.org/10.64066/kobrareports.26.0019