Differences in the Association of Lifestyle-Related Modifiable Risk Factors with Incident Cardiovascular Disease Between Individuals with and without Diabetes.

AIMS: Individuals with diabetes have a high risk of developing cardiovascular disease (CVD). Little was known whether the association between modifiable risk factors and incident CVD would change according to the presence of diabetes. METHODS: In this study, we analyzed 4,132,006 individuals including 173,262 individuals (4.2%) with diabetes registered in the JMDC Claims Database, and compared the association between modifiable risk factors and risk of CVD between individuals with and without diabetes. RESULTS: The median age was 44 years, and 57.5% were men. Multivariable Cox regression analyses showed that the relationship of obesity, hypertension, and dyslipidemia with incident CVD was attenuated in individuals with diabetes, whereas that of non-ideal eating habits, smoking, and physical inactivity with incident CVD was pronounced in those with diabetes. The hazard ratio per 1-point increase in non-ideal lifestyle-related factors was 1.03 [95% confidence interval (CI) 1.03-1.04] in individuals with non-diabetes, whereas 1.09 [95% CI 1.07-1.11] in individuals with diabetes (p-value for interaction < 0.001). Further, hazard ratios for developing CVD were 1.02 [95% 1.01-1.04] in individuals not having diabetes, whereas 1.09 [95% CI 1.04-1.13] in individuals having diabetes for the increase of lifestyle-related factor after 1-year follow-up (p-value for interaction 0.007). CONCLUSION: Our analysis utilizing a nationwide epidemiological dataset presented that the relationship of lifestyle-related factors with incident CVD would be pronounced in people having diabetes, suggesting that the maintenance of a healthy lifestyle would play a more important role in the development of CVD in individuals having diabetes. (244 words).

Our investigation utilizing a nationwide epidemiological cohort showed a pronounced relationship of lifestyle-related factors with incident CVD in individuals with diabetes. The HRs (95% CI) for the occurrence of CVD events showed a progressive increase with each additional lifestyle-related factor. This trend was more prominent among individuals with diabetes than those without diabetes. The association between changes in the number of lifestyle-related factors over a year and the risk of developing CVD was also more pronounced in individuals with diabetes. These results suggest that maintaining healthy lifestyle habits would be more important for the CVD prevention in individuals having diabetes.

Serum interleukin-6 levels at the start of the second course of atezolizumab plus bevacizumab therapy predict therapeutic efficacy in patients with advanced hepatocellular carcinoma: a multicenter analysis.

BACKGROUND AND AIM: Serum interleukin-6 (IL-6) before the administration of atezolizumab plus bevacizumab (Atez + Bev) is a prognostic biomarker in patients with hepatocellular carcinoma (HCC) treated with Atez + Bev. We previously revealed that the neutrophil-to-lymphocyte ratio and serum chemokine levels during treatment with Atez + Bev were more useful as prognostic biomarkers. Therefore, we examined the predictive ability of serum IL-6 for the efficacy of Atez + Bev in patients with HCC. METHODS: We enrolled 94 patients with HCC who received treatment with Atez + Bev. Initial responses were assessed through dynamic computed tomography or magnetic resonance imaging. The levels of IL-6 in serum were measured before and at the initiation of the second course of Atez + Bev. Subsequently, the relationship of IL-6 levels with treatment efficacy was evaluated. RESULTS: IL-6 levels at the initiation of the second course tended to be higher in patients with progressive disease versus those with non-progressive disease in the initial evaluation (P = 0.054). Moreover, the cutoff value (7.4 pg/mL) was useful in stratifying patients by overall survival (i.e. low vs high: not reached vs 21.4 months, respectively, P = 0.001) and progression-free survival (low vs high: 11.9 vs 5.2 months, respectively, P = 0.004). This result was reproduced in patients with HCC who received Atez + Bev as first-line therapy. In the multivariate analyses, IL-6 levels at the initiation of the second course were independent predictive factors for progression-free and overall survival. CONCLUSIONS: Serum levels of IL-6 at the initiation of the second course of treatment may predict Atez + Bev efficacy and prognosis in HCC.

Relationship between the Thermodynamic Quantities and Coordination Structure of Oxide Ions in CaCl2-Based Chloride Melts.

Measuring the thermodynamic quantities and coordination structure of oxide ions in CaCl2-based melts is essential for comprehensively understanding the relationship between the thermodynamic and microscopic behaviors of high-temperature molten salts. In this study, the standard formal chemical potentials of oxide ion, µO2- o', and activity coefficient, γO2- , in NaCl-CaCl2, NaCl-KCl-CaCl2, and LiCl-KCl-CaCl2 melts at 873 K, were evaluated by measuring the dependence of potential of O2/O2- on the oxygen partial pressure by using non-consumable ceramic electrodes; the µO2- o' was -527 ± 0.3, - 535 ± 0.1, and -538 ± 0.2 kJ mol-1 and the γO2- was 0.10, 0.30, and 0.45 for each melt. In addition, the coordination structure of oxide ions in each melt was investigated by combining high-temperature Raman spectroscopy and density functional theory calculations. The coordination structures of oxide ions were identified as [NaO2]3- and [CaOCl3]3- in the NaCl-CaCl2 melt, [CaOCl2]2- in the NaCl-KCl-CaCl2 melt, and [LiCaO]+ and [Li3KO]2+ in the LiCl-KCl-CaCl2 melt, revealing that the stable structure was significantly different depending on the melt composition. The activity coefficients showed a tendency to depend on the nearest-neighbor cation coordinated with the oxide ion. The reported data will provide insights into the physicochemical properties of high-temperature melts and contribute to controlling the compatibility of materials and melts in pyrochemical engineering processes.

Understanding the Manufacturing Process of Lipid Nanoparticles for mRNA Delivery Using Machine Learning.

Lipid nanoparticles (LNPs), used for mRNA vaccines against severe acute respiratory syndrome coronavirus 2, protect mRNA and deliver it into cells, making them an essential delivery technology for RNA medicine. The LNPs manufacturing process consists of two steps, the upstream process of preparing LNPs and the downstream process of removing ethyl alcohol (EtOH) and exchanging buffers. Generally, a microfluidic device is used in the upstream process, and a dialysis membrane is used in the downstream process. However, there are many parameters in the upstream and downstream processes, and it is difficult to determine the effects of variations in the manufacturing parameters on the quality of the LNPs and establish a manufacturing process to obtain high-quality LNPs. This study focused on manufacturing mRNA-LNPs using a microfluidic device. Extreme gradient boosting (XGBoost), which is a machine learning technique, identified EtOH concentration (flow rate ratio), buffer pH, and total flow rate as the process parameters that significantly affected the particle size and encapsulation efficiency. Based on these results, we derived the manufacturing conditions for different particle sizes (approximately 80 and 200 nm) of LNPs using Bayesian optimization. In addition, the particle size of the LNPs significantly affected the protein expression level of mRNA in cells. The findings of this study are expected to provide useful information that will enable the rapid and efficient development of mRNA-LNPs manufacturing processes using microfluidic devices.

Significance of eGFR and proteinuria for cardiovascular disease in individuals beyond 85 years.

BACKGROUND: There are limited data on how advancing age influences prediction of CVD risk based on the estimated glomerular filtration rate (eGFR) and proteinuria, especially in older adults, including those aged ≥ 85 years. This study aimed to clarify the association of eGFR and proteinuria with CVD outcomes and the impact of age on this association. METHODS: The distribution of eGFR and urine protein in Japan was assessed retrospectively using real-world administrative claims and health checkup data collected between April 2014 and November 2022. We investigated the associations of these two parameters with the incidence of CVD, with an emphasis on the impact of aging. RESULTS: We assessed 1 829 020 individuals for distribution of eGFR and proteinuria; after excluding those with known CVD, their association with CVD risk was examined in 1 040 101 individuals aged ≥ 40 years. The prevalence of impaired kidney function (eGFR <60 mL/min/1.73 m2) increased with age, being 0.7%, 9.2%, 21.9%, 40.2%, and 60.2% at the ages of 18-39, 40-64, 65-74, 75-84, and ≥ 85 years (P for trend < 0.001); similarly, the proportion with positive proteinuria increased with age, being 2.7%, 4.3%, 5.6%, 9.2%, and 15.8%, respectively (P for trend < 0.001). Both eGFR and urine protein were identified to be independent risk factors for CVD. Hazard ratios for CVD increased significantly when eGFR was <45 mL/min/1.73 m2 at the ages of 40-64, 65-74, and 75-84 and <30 mL/min/1.73 m2 at ≥ 85 years, while proteinuria remained significantly associated with a high CVD risk regardless of age. These findings were consistent even when analyzed separately by sex. CONCLUSIONS: This study identified eGFR and urine dipstick proteinuria to be independent risk factors for CVD, even among individuals aged ≥ 85 years. However, the contribution of eGFR to the CVD risk was attenuated by aging, whereas proteinuria remained less affected by advancing age.

Age-Dependent Relationship of Physical Inactivity with Incident Cardiovascular Disease: Analysis of a Large Japanese Cohort.

BACKGROUND: There have been limited studies examining age-dependent associations between physical inactivity and cardiovascular disease (CVD). We aimed to clarify the age-dependent relationship of physical inactivity with incident CVD. METHODS: We analyzed 1,097,424 participants aged 18-105 years without a history of CVD enrolled in the DeSC database (median age, 63 years; 46.4% men). We categorized participants into the following 4 groups based on age: ≤44 years (n=203,835), 45-64 years (n=403,619), 65-79 years (n=437,236), ≥80 years (n=52,734). We used three physical inactivity components gained from the self-reported questionnaire during a health checkup. The outcomes were composite CVD events including myocardial infarction, stroke, and heart failure, and each CVD event. RESULTS: During a mean follow-up of 3.2±1.9 years, 81,649 CVD events were observed. The hazard ratios of three physical inactivity components for CVD events increased with age category (P for interaction <0.001). For example, the hazard ratio (95% confidence interval) of physical inactivity defined as not doing light, sweaty exercise for 30 minutes at least twice a week for incident CVD in the groups aged ≤44 years, 45-64 years, 65-79 years, and ≥80 years were 0.97 (0.88-1.05), 1.08 (1.05-1.12), 1.12 (1.10-1.15), and 1.17 (1.12-1.21), respectively (P for interaction <0.001). This association was consistent across subtypes of CVD, including heart failure, myocardial infarction, and stroke. CONCLUSIONS: The association of physical inactivity with a higher risk of developing CVD increased with age. Preventive efforts for physical activity optimization may be more valuable in older people.

Chronic Tonsillitis and IgA Nephropathy: Findings From a Nationwide Japanese Cohort Study.

RATIONALE & OBJECTIVE: Little is known regarding the association between chronic tonsillitis and the onset of IgA nephropathy (IgAN). In the present study, we examined the potential relationship between chronic tonsillitis and a subsequent risk of developing IgAN. STUDY DESIGN: Observational cohort study. SETTING: & Participants: 4,311,393 individuals without a history of IgAN identified between January 2005 to May 2022 within a Japanese nationwide epidemiological database, the JMDC Claims Database, representing health claims to over 60 insurers. EXPOSURE: Comorbid chronic tonsillitis based on diagnosis codes. OUTCOME: IgAN occurrence. ANALYTICAL APPROACH: Cause-specific Cox proportional hazards analysis adjusting for potential confounding factors were employed to estimate hazard ratios (HRs). RESULTS: Comorbid chronic tonsillitis was identified in 12,842 individuals, constituting 0.3% of the cohort. The cohort had a median age of 44 years (interquartile range: 36-53), and males accounted for 57.9%, with a follow-up of 1,089 days (interquartile range: 532-1,797), during which 2,653 cases of IgAN developed. Cumulative incidence curve showed a higher cumulative incidence of IgAN in individuals with chronic tonsillitis compared to their counterparts without this condition. Multivariable cause-specific analysis further demonstrated that individuals with chronic tonsillitis had an elevated risk of developing IgAN, with a HR of 2.72 (95% confidence interval: 1.79-4.14). LIMITATIONS: Potential residual confounders, and lack of consideration for ethnic distinctions. CONCLUSIONS: Using a largescale epidemiological dataset, these findings suggest a relationship between chronic tonsillitis and an elevated risk of IgAN development in the general Japanese population.

Prevalence and relevance of cachexia as diagnosed by two different definitions in patients undergoing hemodialysis: A retrospective and exploratory study.

OBJECTIVE: Cachexia is present in various chronic diseases and is associated with decreased quality of life and increased risk of morbidity and mortality. However, evidence regarding the association of cachexia with prognosis in patients undergoing hemodialysis is limited. We assessed cachexia using two definitions and compared prevalence, functional impairment, and prognostic impact in patients undergoing hemodialysis. METHODS: We enrolled outpatients undergoing hemodialysis at two centers retrospectively. We assessed cachexia using the conventional cachexia (Evans' criteria) and the Asian Working Group for Cachexia (AWGC) criteria. The study examined all-cause mortality and functional status (Clinical Frailty Scale and short physical performance battery). We used Cox proportional hazards model to examine the association with prognosis, and logistic regression analysis to examine the association with functional impairment. RESULTS: Among 367 patients (mean age, 67 years; 63 % male), cachexia prevalence, as defined by Evans' criteria and AWGC, was 21.3 % and 35.2 %, respectively. Cachexia as defined by Evans' criteria was associated with an increased risk of all-cause mortality (hazard ratio [HR], 95 % confidence interval [CI]: 1.81, 1.02-3.23). Also, cachexia as defined by AWGC criteria showed suggestive association with increasing mortality (HR, 95 % CI: 1.56, 0.90-2.70). Similar results were seen between cachexia and functional impairment. CONCLUSIONS: Among patients on hemodialysis, cachexia was highly prevalent and was associated with poor prognosis and functional impairment. Detecting cachexia in earlier stages may be useful for risk stratification in this population.

Change in Body Mass Index and Cardiovascular Outcomes in Patients With Cancer.

OBJECTIVE: To investigate the association between body mass index (BMI) changes and the risk of cardiovascular disease (CVD) in patients with cancer. PATIENTS AND METHODS: This retrospective observational study used data from the JMDC Claims Database obtained between January 2005, and April 2021. We included 52,344 individuals (median [IQR] age, 53 years [46 to 60 years]; 23,584 [45.1%] men) with cancer and no prior CVD. Patients were classified into 3 groups based on the percentage change in BMI from the initial health checkup to the checkup 1 year later: -5.0% or less (BMI loss), -5.0% to 5.0% (stable BMI), and 5.0% or more (BMI gain). The primary end point was composite CVD events including heart failure, atrial fibrillation, ischemic heart disease, and stroke. RESULTS: During a median follow-up period of 763 days (IQR, 369 to 1274 days), 3124 composite CVD events were observed. Compared with stable BMI, the hazard ratios (HRs) of BMI loss and gain for CVD events were 1.16 (95% CI, 1.00 to 1.34) and 1.10 (95% CI, 0.96 to 1.25), respectively. A U-shaped association was observed between the BMI changes and CVD events, particularly for nonatherosclerotic CVD outcomes including heart failure and atrial fibrillation. Compared with stable BMI, both BMI loss and gain increased the risk of heart failure (HR, 1.30; 95% CI, 1.08 to 1.57 and HR, 1.22; 95% CI, 1.02 to 1.47, respectively) and atrial fibrillation (HR, 1.70; 95% CI, 1.18 to 2.45 and HR, 1.55; 95% CI, 1.07 to 2.24, respectively). CONCLUSION: Cancer survivors with BMI loss and gain were at greater risk of CVD. Body mass index loss is associated with a higher risk of CVD.

A polygenic score method boosted by non-additive models.

Dominance heritability in complex traits has received increasing recognition. However, most polygenic score (PGS) approaches do not incorporate non-additive effects. Here, we present GenoBoost, a flexible PGS modeling framework capable of considering both additive and non-additive effects, specifically focusing on genetic dominance. Building on statistical boosting theory, we derive provably optimal GenoBoost scores and provide its efficient implementation for analyzing large-scale cohorts. We benchmark it against seven commonly used PGS methods and demonstrate its competitive predictive performance. GenoBoost is ranked the best for four traits and second-best for three traits among twelve tested disease outcomes in UK Biobank. We reveal that GenoBoost improves prediction for autoimmune diseases by incorporating non-additive effects localized in the MHC locus and, more broadly, works best in less polygenic traits. We further demonstrate that GenoBoost can infer the mode of genetic inheritance without requiring prior knowledge. For example, GenoBoost finds non-zero genetic dominance effects for 602 of 900 selected genetic variants, resulting in 2.5% improvements in predicting psoriasis cases. Lastly, we show that GenoBoost can prioritize genetic loci with genetic dominance not previously reported in the GWAS catalog. Our results highlight the increased accuracy and biological insights from incorporating non-additive effects in PGS models.

The Current Achievements of Multi-Gene Panel Tests in Clinical Settings for Patients with Non-Small-Cell Lung Cancer.

Some multi-gene panel tests have been implemented in clinical settings to guide targeted therapy in non-small-cell lung cancer (NSCLC) in Japan. The current performance of multi-gene panel tests under the condition that the Oncomine Dx Target Test (ODxTT) and Amoy Dx® Pan Lung Cancer PCR panel (AmoyDx-multi) are available remains relatively unknown. We retrospectively reviewed consecutive patients with NSCLC, whose FFPE samples were considered for genetic testing. We assessed the submission rates, the success rates, and the driver oncogene detection rates of multi-gene panel tests. A total of 225 patients were histologically newly diagnosed with NSCLC or diagnosed with a recurrence of NSCLC without a previous multi-gene panel test at our institution. Among the 225 patients, the FFPE samples of 212 patients (94.2%) were submitted for multi-gene panel testing, including 191 samples (84.9%) for the ODxTT and 21 samples (9.3%) for the AmoyDx-multi. Among the 212 samples submitted to multi-gene panel tests, the success rate was 99.5% (211/212). The detection rate of driver oncogene alterations for all histologies was 52.4% (111/212), and that for adenocarcinoma was 69.7% (106/152). A favorable submission rate and success rate of multi-gene panel tests were shown, along with a favorable detection rate in recent clinical settings.

Integration of Computational Pipeline to Streamline Efficacious Drug Nomination and Biomarker Discovery in Glioblastoma.

Glioblastoma multiforme (GBM) is the deadliest, most heterogeneous, and most common brain cancer in adults. Not only is there an urgent need to identify efficacious therapeutics, but there is also a great need to pair these therapeutics with biomarkers that can help tailor treatment to the right patient populations. We built patient drug response models by integrating patient tumor transcriptome data with high-throughput cell line drug screening data as well as Bayesian networks to infer relationships between patient gene expression and drug response. Through these discovery pipelines, we identified agents of interest for GBM to be effective across five independent patient cohorts and in a mouse avatar model: among them are a number of MEK inhibitors (MEKis). We also predicted phosphoglycerate dehydrogenase enzyme (PHGDH) gene expression levels to be causally associated with MEKi efficacy, where knockdown of this gene increased tumor sensitivity to MEKi and overexpression led to MEKi resistance. Overall, our work demonstrated the power of integrating computational approaches. In doing so, we quickly nominated several drugs with varying known mechanisms of action that can efficaciously target GBM. By simultaneously identifying biomarkers with these drugs, we also provide tools to select the right patient populations for subsequent evaluation.

Surface terminations control charge transfer from bulk to surface states in topological insulators.

Topological insulators (TI) hold significant potential for various electronic and optoelectronic devices that rely on the Dirac surface state (DSS), including spintronic and thermoelectric devices, as well as terahertz detectors. The behavior of electrons within the DSS plays a pivotal role in the performance of such devices. It is expected that DSS appear on a surface of three dimensional(3D) TI by mechanical exfoliation. However, it is not always the case that the surface terminating atomic configuration and corresponding band structures are homogeneous. In order to investigate the impact of surface terminating atomic configurations on electron dynamics, we meticulously examined the electron dynamics at the exfoliated surface of a crystalline 3D TI (Bi 2 Se 3 ) with time, space, and energy resolutions. Based on our comprehensive band structure calculations, we found that on one of the Se-terminated surfaces, DSS is located within the bulk band gap, with no other surface states manifesting within this region. On this particular surface, photoexcited electrons within the conduction band effectively relax towards DSS and tend to linger at the Dirac point for extended periods of time. It is worth emphasizing that these distinct characteristics of DSS are exclusively observed on this particular surface.

Comparison of incident hypertension between SGLT2 inhibitors vs. DPP4 inhibitors.

Although several randomized clinical trials have reported the potential benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing blood pressure (BP), whether SGLT2i can reduce incident hypertension is unknown. We analyzed individuals with diabetes who were newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of hypertension. A propensity score matching algorithm was employed to compare the subsequent development of hypertension between the SGLT2i and DPP4i groups. After propensity score matching, 5708 well-balanced pairs of SGLT2i and DPP4i users were identified. SGLT2i administration was associated with a reduced risk of hypertension (HR 0.91, 95% CI: 0.84-0.97). The advantage of SGLT2i use over DPP4i use for incident hypertension was generally consistent in several sensitivity analyses, and subgroup analyses showed that SGLT2i use was significantly associated with a lower risk of hypertension in men, patients with baseline HbA1c of <7.5%, and baseline systolic blood pressure ≥127 mmHg. Our investigation using nationwide real-world data demonstrated the potential advantage of SGLT2i over DPP4i in reducing the development of hypertension in individuals with diabetes.

Risk of cancer history in cardiovascular disease among individuals with hypertension.

Hypertension is the leading risk factor for cardiovascular disease (CVD). Although cancer has recently been increasingly recognized as a novel risk factor for CVD events, little is known about whether co-morbid cancer in individuals with hypertension could further increase the risk of CVD events. We sought to determine the association between the cancer history and the risk of CVD in individuals with hypertension. We retrospectively analyzed a large cohort of 747,620 individuals diagnosed with hypertension from January 2005 through May 2022 using the JMDC Claims Database. Composite CVD events, including myocardial infarction (MI), angina pectoris (AP), stroke, heart failure (HF), and atrial fibrillation (AF), were recorded, and a Cox proportional hazard regression was done to estimate hazard ratios (HR) based on the history of cancer and chemotherapy. 26,531 individuals had a history of cancer. During the mean follow-up period of 1269 ± 962 days, 67,154 composite CVD events were recorded. Compared with individuals without a cancer history, cancer survivors had a higher risk of developing composite CVD events (HR: 1.21, 95% confidence interval [CI]: 1.17-1.26). The HRs (95% CIs) associated with cancer history for MI, AP, stroke, HF, and AF were 1.07 (0.90-1.27), 1.13 (1.06-1.20), 1.14 (1.06-1.24), 1.31 (1.25-1.38), and 1.22 (1.10-1.35), respectively. Lastly, individuals who had received chemotherapy for cancer had a particularly higher risk of developing CVD compared to those who did not undergo chemotherapy. A history of cancer was associated with a greater risk of developing CVD among individuals with hypertension.

Awareness of Being Prescribed Antihypertensive Medications and Cardiovascular Outcomes.

BACKGROUND: Hypertension is a major cause of cardiovascular disease (CVD). In patients with hypertension, unawareness of the disease often results in poor blood pressure control and increases the risk of CVD. However, data in nationwide surveys regarding the proportion of unaware individuals and the implications of such on their clinical outcomes are lacking. We aimed to clarify the association between unawareness of being prescribed antihypertensive medications among individuals taking antihypertensive medications and the subsequent risk of developing CVD.Methods and Results: This retrospective cohort study analyzed data from the JMDC Claims Database, including 313,715 individuals with hypertension treated with antihypertensive medications (median age 56 years). The primary endpoint was a composite of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Overall, 19,607 (6.2%) individuals were unaware of being prescribed antihypertensive medications. During the follow-up period, 33,976 composite CVD endpoints were documented. Despite their youth, minimal comorbidities, and the achievement of better BP control with a reduced number of antihypertensive prescriptions, unawareness of being prescribed antihypertensive medications was associated with a greater risk of developing composite CVD. Hazard ratios of unawareness of being prescribed antihypertensive medications were 1.16 for myocardial infarction, 1.25 for angina pectoris, 1.15 for stroke, 1.36 for heart failure, and 1.28 for atrial fibrillation. The results were similar in several sensitivity analyses, including the analysis after excluding individuals with dementia. CONCLUSIONS: Among individuals taking antihypertensive medications, assessing the awareness of being prescribed antihypertensive medications may help identify those at high risk for CVD-related events.

Sex Differences in the Association Between Depression and Incident Cardiovascular Disease.

Background: Depression is a known risk factor for cardiovascular disease (CVD), but the potential sex differences in this association remain unclear. Objectives: The aim of this study was to investigate the association between depression and subsequent CVD events, and to explore potential sex differences. Methods: The authors conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4,125,720 individuals aged 18 to 75 years without a history of cardiovascular disease or renal failure and missing data at baseline. Participants were followed up for a mean of 1,288 days to assess the association between depression and subsequent CVD events, such as myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Results: Our analysis revealed a significant association between depression and subsequent composite CVD events in both men and women, with a stronger association observed in women. The HR for the composite endpoint was 1.64 (95% CI: 1.59-1.70) in women and 1.39 (95% CI: 1.35-1.42) in men after multivariable adjustment (P for interaction <0.001). Furthermore, the individual components of the composite endpoint were also associated with depression in both men and women, each of which was also observed to be more strongly associated in women. Conclusions: Our study provides evidence of a significant association between depression and subsequent CVD events in both men and women, with a more pronounced association observed in women. These findings highlight the importance of addressing depression and tailoring prevention and management strategies according to sex-specific factors.

Unawareness of being prescribed medications for diabetes and incident cardiovascular disease.

BACKGROUND: Some patients with diabetes are unaware that they are prescribed medications for diabetes. The purpose of this study is to determine, using a Japanese nationwide epidemiologic database, the association between unawareness of being prescribed medication for diabetes and the risk of developing cardiovascular disease (CVD) in patients with diabetes. METHODS: This observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2022, including 94,048 patients with diabetes treated with medications. The primary endpoint was a composite endpoint including myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF). RESULTS: We identified 7561 composite CVD endpoints during a mean follow-up of 1199 ±â€¯902 days. Overall, 7779 (8.3 %) patients were unaware of being prescribed medications for diabetes. Those who did not know they were prescribed drugs were younger and had better glycemic control, but these individuals were at higher risk of developing combined CVD [hazard ratio (HR) 1.13, 95 % confidence interval (95 % CI) 1.04-1.22]. HRs of unawareness of being prescribed medications for diabetes were 1.33 (95 % CI 1.06-1.68) for MI, 1.13 (95 % CI 0.97-1.31) for stroke, 1.10 (95 % CI 1.00-1.21) for HF, and 1.19 (95 % CI 0.97-1.47) for AF, respectively. CONCLUSIONS: In patients with diabetes taking medications for diabetes, even if they are young and have good glycemic control, unawareness of being prescribed medications for diabetes was associated with a greater risk of developing CVD. It is important that they receive adequate education from their healthcare providers to accurately identify their treatment status.

Photoelectron Imaging Signature for Selective Formation of Icosahedral Anionic Silver Cages Encapsulating Group 5 Elements: M@Ag12- (M = V, Nb, and Ta).

An assembly of 13 atoms can form highly symmetric architectures like those belonging to D3h, Oh, D5h, and Ih point groups. Here, using photoelectron imaging spectroscopy in combination with density functional theory (DFT) calculations, we present a simple yet convincing experimental signature for the selective formation of icosahedral cages of anionic silver clusters encapsulating a dopant atom of group 5 elements: M@Ag12- (M = V, Nb, and Ta). Their photoelectron images obtained at 4 eV closely resemble one another: only a single ring is observed, which is assignable to photodetachment signals from a 5-fold degenerate superatomic 1D electronic shell in the 1S21P61D10 configuration of valence electrons. The perfect degeneracy represents an unambiguous fingerprint of an icosahedral symmetry, which would otherwise be lifted in all of the other structural isomers. DFT calculations confirm that Ih forms are the most stable and that D5h, Oh, and D3h structures are not found even in metastable states.