Atomic-Scale Scanning of Domain Network in the Ferroelectric HfO2 Thin Film.

Ferroelectric HfO2-based thin films have attracted much interest in the utilization of ferroelectricity at the nanoscale for next-generation electronic devices. However, the structural origin and stabilization mechanism of the ferroelectric phase are not understood because the film is typically nanocrystalline with active yet stochastic ferroelectric domains. Here, electron microscopy is used to map the in-plane domain network structures of epitaxially grown ferroelectric Y:HfO2 films in atomic resolution. The ferroelectricity is confirmed in free-standing Y:HfO2 films, allowing for investigating the structural origin for their ferroelectricity by 4D-STEM, high-resolution STEM, and iDPC-STEM. At the grain boundaries of <111>-oriented Pca21 orthorhombic grains, a high-symmetry mixed-(R3m, Pnm21) phase is induced, exhibiting enhanced polarization due to in-plane compressive strain. Nanoscale Pca21 orthorhombic grains and their grain boundaries with mixed-(R3m, Pnm21) phases of higher symmetry cooperatively determine the ferroelectricity of the Y:HfO2 film. It is also found that such ferroelectric domain networks emerge when the film thickness is beyond a finite value. Furthermore, in-plane mapping of oxygen positions overlaid on ferroelectric domains discloses that polarization is suppressed at vertical domain walls, while it is active when domains are aligned horizontally with subangstrom domain walls. In addition, randomly distributed 180° charged domain walls are confined by spacer layers.

Three-year outcomes following non-ST-segment elevation myocardial infarction and new-generation drug-eluting stent implantation, stratified by patient age (under and over 75 years) and left ventricular ejection fraction: A prospective cohort study.

Due to limited published data, we investigated 3-year outcomes according to left ventricular ejection fraction (LVEF) in patients older and younger than 75 years with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent successful newer-generation drug-eluting stent (DES) implantation. This research analyzed the data of 4558 patients (1032 older adults [≥75 years] and 3526 younger adults [<75 years]) from the Korea Acute MI Registry-NIH. We further divided the older group based on LVEF: heart failure (HF) with reduced EF (HFrEF, ≤40%, n = 196; group A), HF with mildly reduced EF (HFmrEF, 41-49%, n = 228; group B), and HF with preserved EF (HFpEF, ≥50%, n = 608; group C). Similarly, the younger group was divided into HFrEF (group D, n = 353), HFmrEF (group E, n = 577), and HFpEF (group F, n = 2596). The primary outcome was a composite of major adverse cardiac events (MACE) at 3 years, including all-cause death, recurrent MI, any repeat revascularization, or hospitalization for HF. MACE rates were highest in the HFrEF groups (A and D), followed by the HFmrEF groups (B and E), and lowest in the HFpEF groups (C and F) for both age groups. All-cause death, cardiac death (CD), all-cause death or MI, and hospitalization for HF rates were higher in group A than in groups B and C, and higher in group D than in groups E and F. Across all LVEF categories, MACE, all-cause death, CD, and non-CD, and all-cause death or MI rates were higher in the older group. This multicenter cohort study demonstrates that older patients have higher mortality rates compared to younger patients. Additionally, MACE rates were highest in the HFrEF group, followed by the HFmrEF group, and lowest in the HFpEF group across both age groups. Further research is needed to confirm these findings.

Expansion microscopy of axonemal dyneins in islet primary cilia.

Primary cilia are sensory organelles that mediate critical cellular functions yet are difficult to visualize because of their small size and low abundance. Expansion microscopy (ExM) is an imaging method that physically expands biological specimens using a swellable hydrogel, facilitating downstream imaging of small cellular structures. In this study, we apply ExM with confocal imaging to probe axonemal dynein expression in murine and human pancreatic islets. Innovations include an updated ExM workflow adapted from 2D cultured cells to 3D tissue optimized for intact pancreatic islets, and demonstration of axonemal dynein protein expression in islet primary cilia and centrioles. Four dynein subunits were consistently detected in both expanded and nonexpanded samples across species, including DNAI1, DNAH5, DNAH11, and DNALI1, where DNAI1 expression was the most readily detectable and seen to exhibit a distinct ring-like symmetry on super-resolution imaging. We discuss technical issues contributing to ExM success, including antibody performance across ExM and conventional sample preparation and imaging protocols, and the need to validate findings using gene knockdowns and controls. We conclude that ExM is a useful approach for identifying ciliary proteins in pancreatic islet tissue and may be broadly applicable to studying protein composition of other organelles.

Antibacterial Immunonegative Coating with Biocompatible Materials on a Nanostructured Titanium Plate for Orthopedic Bone Fracture Surgery.

Periprosthetic infections resulting from bacterial biofilm formation following surgical bone fracture fixation present important clinical challenges. Conventional orthopedic implant materials, such as titanium, are prone to biofilm formation. This study introduces a novel surface for orthopedic titanium plates, optimized for clinical application in human bone fractures. Leveraging nanostructure-based surface coating technology, the plate achieves an antibacterial/immunonegative surface using biocompatible materials, including poloxamer 407, epigallocatechin gallate, and octanoic acid. These materials demonstrate high biocompatibility and thermal stability after autoclaving. The developed plate, named antibacterial immunonegative surface, releases antibacterial agents and prevents adhesion between human tissue and metal surfaces. Antibacterial immunonegative surface plates exhibit low cell toxicity, robust antibacterial effects against pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, high resistance to biofilm formation on the implant surface and surrounding tissues, and minimal immune reaction in a rabbit femoral fracture model. This innovation holds promise for addressing periprosthetic infections and improving the performance of orthopedic implants.

Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation.

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Renin-angiotensin system inhibitors and non-ST-elevation myocardial infarction outcomes based on left ventricular ejection fraction.

BACKGROUND: We assessed left ventricular ejection fraction (LVEF) to compare the effects of renin-angiotensin system inhibitors (RASI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We categorized 4558 patients with NSTEMI as either RASI users (3752 patients) or non-users (806 patients). The 3-year patient-oriented composite outcome (POCO), which included all-cause death, recurrent myocardial infarction, any repeat revascularization, or hospitalization for heart failure (HF), was the primary outcome. To compare clinical outcomes, a multivariable-adjusted hazard ratio (aHR) was calculated after performing multicollinearity tests on all significant confounding variables (P < 0.05). RESULTS: Among RASI users, the aHRs for POCO, all-cause death, and cardiac death were significantly higher in the HF with reduced EF (HFrEF) subgroup than in the HF with mildly reduced EF (HFmrEF) (1.610, 2.120, and 2.489; P < 0.001, <0.001, and <0.001; respectively) and HF with preserved EF (HFpEF) (2.234, 3.920, and 5.215; P < 0.001, <0.001, and <0.001; respectively) subgroups. The aHRs for these variables were significantly higher in the HFmrEF subgroup than the HFpEF subgroup (1.416, 1.843, and 2.172, respectively). Among RASI non-users, the aHRs for these variables were significantly higher in the HFrEF subgroup than the HFmrEF (2.573, 3.172, and 3.762, respectively) and HFpEF (2.425, 3.805, and 4.178, respectively) subgroups. In three LVEF subgroups, RASI users exhibited lower aHRs for POCO and all-cause death than RASI non-users. CONCLUSION: In the RASI users group, the aHRs for POCO and mortality were highest in the HFrEF subgroup, intermediate in the HFmrEF subgroup, and lowest in the HFpEF subgroup.

Assessing the Impact of Defacing Algorithms on Brain Volumetry Accuracy in MRI Analyses.

Background and Purpose: To ensure data privacy, the development of defacing processes, which anonymize brain images by obscuring facial features, is crucial. However, the impact of these defacing methods on brain imaging analysis poses significant concern. This study aimed to evaluate the reliability of three different defacing methods in automated brain volumetry. Methods: Magnetic resonance imaging with three-dimensional T1 sequences was performed on ten patients diagnosed with subjective cognitive decline. Defacing was executed using mri_deface, BioImage Suite Web-based defacing, and Defacer. Brain volumes were measured employing the QBraVo program and FreeSurfer, assessing intraclass correlation coefficient (ICC) and the mean differences in brain volume measurements between the original and defaced images. Results: The mean age of the patients was 71.10±6.17 years, with 4 (40.0%) being male. The total intracranial volume, total brain volume, and ventricle volume exhibited high ICCs across the three defacing methods and 2 volumetry analyses. All regional brain volumes showed high ICCs with all three defacing methods. Despite variations among some brain regions, no significant mean differences in regional brain volume were observed between the original and defaced images across all regions. Conclusions: The three defacing algorithms evaluated did not significantly affect the results of image analysis for the entire brain or specific cerebral regions. These findings suggest that these algorithms can serve as robust methods for defacing in neuroimaging analysis, thereby supporting data anonymization without compromising the integrity of brain volume measurements.

Effect of diabetes mellitus on 3-year outcomes in patients with acute myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Diabetes mellitus (DM) is a significant factor in increased mortality rates among patients with acute myocardial infarction (AMI), but research on its impact on the long-term outcomes in patients with MI with nonobstructive coronary arteries (MINOCA) is limited. Thus, a comparison of the 3-year clinical outcomes between the DM and non-DM groups among patients with MINOCA was undertaken. METHODS: From the Korea AMI Registry-National Institute of Health dataset, 10,774 AMI patients were enrolled. After applying the exclusion criteria, 379 patients with MINOCA were included. The primary clinical outcomes were major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction (MI), repeat coronary revascularization, and stroke. The secondary outcomes were the individual components of MACCE. RESULTS: The adjusted hazard ratios for 3-year MACCE (2.287, p = 0.010), all-cause death (2.845, p = 0.004), and non-cardiac death (non-CD, 3.914, p = 0.008) were higher in the DM group than in the non-DM group. It is speculated that the higher non-CD rate in the MINOCA group is attributable to a higher proportion of patients with non-ST-segment elevation MI in the total study population. The CD, recurrent MI, revascularization, and stroke rates were similar between the DM and non-DM groups. DM, advanced age, cardiopulmonary resuscitation on admission, and non-use of statin medications were significant predictors of MACCE. CONCLUSIONS: In this study involving patients with MINOCA, the DM group exhibited a higher 3-year mortality rate than the non-DM group. Thus, DM demonstrated a hazardous effect even in patients with MINOCA.

Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival.

Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, three-dimensional hydrogels of crosslinked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger ß1 integrin activation and instead actuate a TGF-ß1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.

Effects of Positive Airway Pressure on Cardiorespiratory Fitness in Patients with Concomitant Obstructive Sleep Apnea and Cardiovascular Disease.

Background and Objectives: Obstructive sleep apnea (OSA) is common in cardiovascular disease (CVD), although positive airway pressure (PAP) treatment has not been demonstrated to improve the cardiovascular outcome. The objective of this study is to investigate the impact of adherence to PAP therapy on cardiopulmonary exercise testing (CPET) performance in patients with concomitant OSA and CVD. Materials and Methods: This preliminary study involved symptomatic OSA patients requiring PAP treatment who had CVD. All subjects underwent polysomnography, echocardiography, and CPET at baseline. After 6 to 12 months of PAP treatment, CPET performance was re-assessed. The changes in CPET parameters before and after PAP treatment were compared between patients who were adherent to PAP and patients who were not adherent to PAP. Results: A total of 16 OSA patients with an apnea-hypopnea index of 32.0 ± 23.4 were enrolled. Patients were classified into the adherent (n = 9) and non-adherent (n = 7) groups with regard to PAP adherence. After 6 to 12 months of PAP treatment, the PAP-adherent group showed a greater increase in peak VO2 than the PAP-non-adherent group, but the difference between the two groups was not significant (p = 0.581). The decrease in ventilatory equivalent for the carbon dioxide slope (VE/VCO2) was significantly greater in the PAP-adherent group compared to the PAP-non-adherent group (p = 0.030). Conclusions: Adherence to PAP therapy for OSA is associated with an improvement in the VE/VCO2 slope, as an index of the ventilatory response to exercise, in patients with CVD. Screening for sleep apnea in CVD patients may be warranted, and strategies to optimize adherence to PAP in these patients are beneficial. Further evidence is needed to elucidate whether CPET could be routinely used to monitor treatment responses of OSA to PAP therapy in patients with CVD.

High prevalence of ALPK3 premature terminating variants in Korean hypertrophic cardiomyopathy patients.

Background: The alpha-protein kinase 3 (ALPK3) gene (OMIM: 617608) is associated with autosomal recessive familial hypertrophic cardiomyopathy-27 (CMH27, OMIM: 618052). Recently, several studies have shown that monoallelic premature terminating variants (PTVs) in ALPK3 are associated with adult-onset autosomal dominant hypertrophic cardiomyopathy (HCMP). However, these studies were performed on patient cohorts mainly from European Caucasian backgrounds. Methods: To determine if this finding is replicated in the Korean HCMP cohort, we evaluated 2,366 Korean patients with non-syndromic HCMP using exome sequencing and compared the cohort dataset with three independent population databases. Results: We observed that monoallelic PTVs in ALPK3 were also significantly enriched in Korean patients with HCMP with an odds ratio score of 10-21. Conclusions: We suggest that ALPK3 PTV carriers be considered a risk group for developing HCMP and be monitored for cardiomyopathies.

Deterministic Orientation Control of Ferroelectric HfO2 Thin Film Growth by a Topotactic Phase Transition of an Oxide Electrode.

The scale-free ferroelectricity with superior Si compatibility of HfO2 has reawakened the feasibility of scaled-down nonvolatile devices and beyond the complementary metal-oxide-semiconductor (CMOS) architecture based on ferroelectric materials. However, despite the rapid development, fundamental understanding, and control of the metastable ferroelectric phase in terms of oxygen ion movement of HfO2 remain ambiguous. In this study, we have deterministically controlled the orientation of a single-crystalline ferroelectric phase HfO2 thin film via oxygen ion movement. We induced a topotactic phase transition of the metal electrode accompanied by the stabilization of the differently oriented ferroelectric phase HfO2 through the migration of oxygen ions between the oxygen-reactive metal electrode and the HfO2 layer. By stabilizing different polarization directions of HfO2 through oxygen ion migration, we can gain a profound understanding of the oxygen ion-relevant unclear phenomena of ferroelectric HfO2.

Comparative proteomics analysis of biofilms and planktonic cells of Enterococcus faecalis and Staphylococcus lugdunensis with contrasting biofilm-forming ability.

Biofilms make it difficult to eradicate bacterial infections through antibiotic treatments and lead to numerous complications. Previously, two periprosthetic infection-related pathogens, Enterococcus faecalis and Staphylococcus lugdunensis were reported to have relatively contrasting biofilm-forming abilities. In this study, we examined the proteomics of the two microorganisms' biofilms using LC-MS/MS. The results showed that each microbe exhibited an overall different profile for differential gene expressions between biofilm and planktonic cells as well as between each other. Of a total of 929 proteins identified in the biofilms of E. faecalis, 870 proteins were shared in biofilm and planktonic cells, and 59 proteins were found only in the biofilm. In S. lugdunensis, a total of 1125 proteins were identified, of which 1072 proteins were found in common in the biofilm and planktonic cells, and 53 proteins were present only in the biofilms. The functional analysis for the proteins identified only in the biofilms using UniProt keywords demonstrated that they were mostly assigned to membrane, transmembrane, and transmembrane helix in both microorganisms, while hydrolase and transferase were found only in E. faecalis. Protein-protein interaction analysis using STRING-db indicated that the resulting networks did not have significantly more interactions than expected. GO term analysis exhibited that the highest number of proteins were assigned to cellular process, catalytic activity, and cellular anatomical entity. KEGG pathway analysis revealed that microbial metabolism in diverse environments was notable for both microorganisms. Taken together, proteomics data discovered in this study present a unique set of biofilm-embedded proteins of each microorganism, providing useful information for diagnostic purposes and the establishment of appropriately tailored treatment strategies. Furthermore, this study has significance in discovering the target candidate molecules to control the biofilm-associated infections of E. faecalis and S. lugdunensis.

Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction.

This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96-1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI.Trial registration: NCT04734028.

Prognostic Impact of CYP2C19 Genotypes on Long-Term Clinical Outcomes in Older Patients After Percutaneous Coronary Intervention.

BACKGROUND: Carriers of CYP2C19 loss-of-function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. METHODS AND RESULTS: The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel-based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3-year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all-cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3-year clinical outcomes. CONCLUSIONS: In older patients, the presence of any CYP2C19 loss-of-function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. REGISTRATION: URL: https://clinicaltrials.gov. Identifier: NCT04734028.

Risk of Head and Neck Cancer in Patients with Psoriasis: A Nationwide Population-based Study.

An association between psoriasis and cancer risk has been suggested in prior studies, but few have focused on head and neck cancers. Using the Korean National Health Insurance Service database, the relevance between psoriasis and head and neck cancer risks was investigated in a cross-sectional study of 3,869,264 individuals over 20 years of age, who received general health examination in 2009 and were followed until 2020. Head and neck cancer incidence rates were compared between individuals with and without psoriasis, and contributing factors were analysed. The head and neck cancer risk was significantly increased in the psoriasis group compared with the non-psoriasis group (hazard ratio [HR] 1.36; 95% confidence interval [CI] 1.07-1.74; p = 0.01) after adjusting for age, sex, body mass index, income, smoking, alcohol, exercise, diabetes mellitus, hypertension and dyslipidaemia. The risk was especially elevated for nasopharyngeal (HR 2.04; 95% CI 1.12-3.70; p = 0.02) and salivary gland cancer (HR 1.96; 95% CI 1.08-3.56; p = 0.03). Alcohol consumption significantly influenced the risk, particularly for oropharyngeal and oral cavity cancer. Our study provides insights into the potential risks of head and neck cancer in patients with psoriasis, which could aid in refining patient management strategies.

Association of Age- and Body Mass Index-Stratified High On-Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients.

BACKGROUND: Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on-treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. METHODS AND RESULTS: The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m2 or >22.6 kg/m2). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106-1.867]; P=0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095-2.290]; P=0.015) compared with the those with non-HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542-0.959]; P=0.024). Meanwhile, patients with HPR with BMI >22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140-1.688]; P=0.001). No differences were shown in major bleeding. CONCLUSIONS: HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

The First Korean Case with Cardiac, Facial, and Digital Anomalies with Developmental Delay Caused by De Novo TRAF7 p.Arg655Gln Variant.

TRAF7-related disorders represent some of the rarest inherited disorders, exhibiting clinical features that overlap with cardiac, facial, and digital anomalies with developmental delay (CAFDADD) syndrome, as well as blepharophimosis-mental retardation syndrome (BMRS). A 36-year-old male, presenting with total blindness, blepharophimosis, and intellectual disability, was admitted for the assessment of resting dyspnea several months previously. He had a history of being diagnosed with obstructive sleep apnea (OSA). Transesophageal and transthoracic echocardiography unveiled right ventricular dilatation without significant pulmonary hypertension, bicuspid aortic valve with aortic root aneurysm, and aortic regurgitation in the proband. Sanger sequencing identified a de novo TRAF7 variant (c.1964G>A; p.Arg655Gln). Subsequently, aortic root replacement using the Bentall procedure was performed. However, despite the surgery, he continued to experience dyspnea. Upon re-evaluating OSA with polysomnography, it was discovered that continuous positive airway pressure support alleviated his symptoms. The underlying cause of his symptoms was attributed to OSA, likely exacerbated by the vertebral anomaly and short neck associated with CAFDADD syndrome. Clinicians should be attentive to the symptoms associated with OSA as it is a potentially serious medical condition in patients with TRAF7 variants.

Application of artificial intelligence in hypertension.

Hypertension is an important modifiable risk factor for morbidity and mortality associated with cardiovascular disease. The incidence of hypertension is increasing not only in Korea but also in many Western countries due to the aging of the population and the increase in unhealthy lifestyles. However, hypertension control rates remain low due to poor adherence to antihypertensive medications, low awareness of hypertension, and numerous factors that contribute to hypertension, including diet, environment, lifestyle, obesity, and genetics. Because artificial intelligence (AI) involves data-driven algorithms, AI is an asset to understanding chronic diseases that are influenced by multiple factors, such as hypertension. Although several hypertension studies using AI have been published recently, most are exploratory descriptive studies that are often difficult for clinicians to understand and have little clinical relevance. This review aims to provide a clinician-centered perspective on AI by showing recent studies on the relevance of AI for patients with hypertension. The review is organized into sections on blood pressure measurement and hypertension diagnosis, prognosis, and management.

The Impact of Polymers on Enzalutamide Solid Self-Nanoemulsifying Drug Delivery System and Improved Bioavailability.

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.