Persistent Severe Headache After Removal of Fungus Ball From the Sphenoid Sinus: A Case Report.

OBJECTIVE: Granulomatous invasive fungal sinusitis (GIFS) is a rare and life-threatening disease, whereas fungus ball (FB) is the most common form of noninvasive fungal sinusitis. Both GIFS and FB primarily develop in immunocompetent patients, with the former associated with higher mortality and morbidity. METHODS: A chart review and review of the literature. RESULTS: We present the case of a 77-year-old woman with mixed fungal sinusitis who was successfully treated with voriconazole. CONCLUSIONS: GIFS and FB can coexist in extremely rare cases, known as mixed fungal sinusitis; however, the diagnosis and subsequent treatment of mixed fungal sinusitis can be delayed because of a lack of awareness of the underlying concept. Therefore, it is crucial for clinicians to recognize the concept of mixed fungal sinusitis.

Differential diagnosis of thyroid nodules using heterogeneity quantification software on ultrasound images: correlation with the Bethesda system and surgical pathology.

Ultrasonography (US)-guided fine-needle aspiration cytology (FNAC) is the primary modality for evaluating thyroid nodules. However, in cases of atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), supplemental tests are necessary for a definitive diagnosis. Accordingly, we aimed to develop a non-invasive quantification software using the heterogeneity scores of thyroid nodules. This cross-sectional study retrospectively enrolled 188 patients who were categorized into four groups according to their diagnostic classification in the Bethesda system and surgical pathology [II-benign (B) (n = 24); III-B (n = 52); III-malignant (M) (n = 54); V/VI-M (n = 58)]. Heterogeneity scores were derived using an image pixel-based heterogeneity index, utilized as a coefficient of variation (CV) value, and analyzed across all US images. Differences in heterogeneity scores were compared using one-way analysis of variance with Tukey's test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristic (AUROC) curve. The results of this study indicated significant differences in mean heterogeneity scores between benign and malignant thyroid nodules, except in the comparison between III-M and V/VI-M nodules. Among malignant nodules, the Bethesda classification was not observed to be associated with mean heterogeneity scores. Moreover, there was a positive correlation between heterogeneity scores and the combined diagnostic category, which was based on the Bethesda system and surgical cytology grades (R = 0.639, p < 0.001). AUROC for heterogeneity scores showed the highest diagnostic performance (0.818; cut-off: 30.22% CV value) for differentiating the benign group (normal/II-B/III-B) from the malignant group (III-M/V&VI-M), with a diagnostic accuracy of 72.5% (161/122). Quantitative heterogeneity measurement of US images is a valuable non-invasive diagnostic tool for predicting the likelihood of malignancy in thyroid nodules, including AUS or FLUS.

Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts.

BACKGROUND: The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. METHODS: 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. RESULTS: The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively. CONCLUSIONS: The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.

Determinants and effects of microvascular obstruction on serial change in left ventricular diastolic function after reperfused acute myocardial infarction.

Background: Although left ventricular (LV) diastolic dysfunction is more related to functional capacity after acute myocardial infarction (AMI), the determinants of LV diastolic functional change after reperfused AMI remain unknown. This study aimed to investigate the effects of microvascular obstruction (MVO) on mid-term changes in LV diastolic function after reperfused AMI. Methods: In a cohort of 72 AMI patients who underwent successful revascularization, echocardiography and cardiovascular magnetic resonance imaging were repeated at 9-month intervals. The late gadolinium enhancement (LGE) amount, segmental extracellular volume fraction, global LV, and left atrial (LA) phasic functions, along with mitral inflow and tissue Doppler measurements, were repeated. Results: Among the included patients, 31 (43%) patients had MVO. During the 9-month interval, LV ejection fraction (EF) and LV global longitudinal strain (GLS) were significantly improved in accordance with a decrease in LGE amount (from 18.2 to 10.3 g, p < 0.001) and LV mass. The deceleration time (DT) of early mitral inflow (188.6 ms-226.3 ms, p < 0.001) and LV elastance index (Ed; 0.133 1/ml-0.127 1/ml, p = 0.049) were significantly improved, but not in conventional diastolic functional indexes. Their improvements occurred in both groups; however, the degree was less prominent in patients with MVO. The degree of decrease in LGE amount and increase in LVEF was significantly correlated with improvement in LV-Ed or LA phasic function, but not with conventional diastolic functional indexes. Conclusions: In patients with reperfused AMI, DT of early mitral inflow, phasic LA function, and LV-Ed were more sensitive diastolic functional indexes. The degree of their improvement was less prominent in patients with MVO.

Status of MyHealthWay and Suggestions for Widespread Implementation, Emphasizing the Utilization and Practical Use of Personal Medical Data.

OBJECTIVES: In the Fourth Industrial Revolution, there is a focus on managing diverse medical data to improve healthcare and prevent disease. The challenges include tracking detailed medical records across multiple institutions and the necessity of linking domestic public medical entities for efficient data sharing. This study explores MyHealthWay, a Korean healthcare platform designed to facilitate the integration and transfer of medical data from various sources, examining its development, importance, and legal implications. METHODS: To evaluate the management status and utilization of MyHealthWay, we analyzed data types, security, legal issues, domestic versus international issues, and infrastructure. Additionally, we discussed challenges such as resource and infrastructure constraints, regulatory hurdles, and future considerations for data management. RESULTS: The secure sharing of medical information via MyHealthWay can reduce the distance between patients and healthcare facilities, fostering personalized care and self-management of health. However, this approach faces legal challenges, particularly relating to data standardization and access to personal health information. Legal challenges in data standardization and access, particularly for secondary uses such as research, necessitate improved regulations. There is a crucial need for detailed governmental guidelines and clear data ownership standards at institutional levels. CONCLUSIONS: This report highlights the role of Korea's MyHealthWay, which was launched in 2023, in transforming healthcare through systematic data integration. Challenges include data privacy and legal complexities, and there is a need for data standardization and individual empowerment in health data management within a systematic medical big data framework.

Corrigendum to "Glucose-lowering effect of Reducose® enriched with 1-deoxynojirimycin and l-leucine: Studies on insulin secretion in INS-1 cells and reduction of blood glucose in diabetic rats" <[Heliyon Volume 10, Issue 3, 15 February 2024, article e25499]>.

[This corrects the article DOI: 10.1016/j.heliyon.2024.e25499.].

ERBB2 Targeting Reveals a Significant Suppression of Tumorigenesis in Murine Endometrial Cancer with Pten Mutation.

Endometrial cancer is the most common gynecologic malignancy. PTEN is a negative regulator of PI3K signaling and is deficient in > 50% of primary human endometrial cancer. Amplification of ERBB2 promotes tumorigenesis and pathogenesis of several human cancers. However, the effect of ERBB2 targeting has not been studied in endometrial cancer with PTEN mutations. The murine model Pgrcre/+Erbb2f/fPtenf/f (Erbb2d/d Ptend/d) was developed to evaluate the effect of ERBB2 targeted therapy in endometrial cancer with PTEN deficiency. Histopathological and molecular analysis was performed for Ptend/d and Erbb2d/dPtend/d mice. Histopathological analysis revealed that Erbb2d/dPtend/d mice significantly reduced development and progression of endometrial cancer compared to Ptend/d mice. Furthermore, percentage of proliferative cells in Erbb2d/dPtend/d mice revealed anti-tumorigenic effect of Erbb2 ablation compared to Ptend/d mice. Our results demonstrate that Erbb2 ablation reveals a significant suppression of tumorigenesis on endometrial cancer of Ptend/d mice. Our results suggest that Erbb2 functions as an oncogene in endometrial cancer of Ptend/d mice implying that Erbb2 targeting can be used as an effective therapeutic approach for treatment of endometrial cancer with PTEN deficiency to hinder cancer development.

Using computed tomogram atrial myocardial thickness maps in high-power short-duration radiofrequency pulmonary vein isolation: UTMOST AF.

Background: High-power short-duration (HPSD) ablation creates wide, shallow lesions using radiofrequency (RF) heating. It is uncertain if adjusting RF energy based on atrial wall thickness provides extra benefits. We studied the safety and effectiveness of tailored HPSD energy based on left atrial (LA) wall thickness (LAWT) for circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF). Methods: We enrolled 212 patients (68.4% male, mean age: 59.5 ± 11.0 years) and randomly assigned them to two groups: LAWT-guided CPVI (WT, n = 108) and conventional CPVI (control, n = 104). Both groups used an open irrigated-tip deflectable catheter to apply 50 W for 10 s to the posterior LA, while controls used 60 W for 15 s on other LA regions. RF delivery time in WT was titrated (15 s at LAWT > 2.1 mm, 13 s at 1.4-2.1 mm, and 11 s at <1.4 mm) according to the computed tomogram-myocardial thickness color map. Results: After a mean follow-up of 13.4 ± 7.0 months, the WT and control groups showed no significant difference regarding clinical recurrence rate (13.9% vs. 5.8%, respectively; p = .061) and major complication rate (4.6% vs. 3.8%, respectively; p > .999). The total procedure time, cardioversion rate, and post-procedural AAD prescription rates did not significantly differ between the groups. Conclusions: The LAWT-guided energy titration strategy did not result in improved procedural safety and efficacy compared to the conventional 50-60 W-HPSD CPVI in patients with PAF.

Association of extra-pulmonary vein triggers with low-voltage area and clinical recurrence in patients with atrial fibrillation undergoing catheter ablation.

Background and Objectives: Although extra-pulmonary vein (PV) triggers (ExPVTs) play a role in atrial fibrillation (AF) recurrence after catheter ablation (AFCA), the mechanism is unknown. We explored whether the locations of ExPVTs were associated with low-voltage scar areas (LVAs). Methods: Among 2255 consecutive patients who underwent a de novo AFCA, 1696 (male 72.1%, median 60 years old, paroxysmal 64.7%) were included who underwent isoproterenol provocation and voltage mapping of the left atrium (LA) during their procedures. We investigated the associations between ExPVTs and their mean LA voltage and colocalization of ExPVTs within LVAs (<0.2 mV). Results: We observed ExPVTs in 181 (10.7%) patients (60 in the LA, 99 in the right atrium [RA], 16 biatrial, and 6 unmappable). A lower mean LA voltage was independently associated with the existence of ExPVTs (OR 0.77 per 1 SD mV increase, 95% CI 0.60-0.99, p = .039). Among 76 patients who had ExPVTs[LA], 43 (56.6%) had ExPVTs within LVAs. During a median of a 42-month follow-up, patients with ExPVTs had a higher AF recurrence than those without (HR 1.87, 95% CI 1.48-2.37, Log-rank p < .001), but colocalization of ExPVTs and LVAs (Log-rank p = .544) and the anatomical location of ExPVTs (Log-rank p = .084) did not affect the rhythm outcome. Conclusions: The presence of ExPVTs was associated with low LA voltage and poor rhythm outcome post-AFCA, but the colocalization of ExPVTs and LVA in LA did not affect rhythm outcome.

Interaction between phytoplankton and heterotrophic bacteria in Arctic fjords during the glacial melting season as revealed by eDNA metabarcoding.

The hydrographic variability in the fjords of Svalbard significantly influences water mass properties, causing distinct patterns of microbial diversity and community composition between surface and subsurface layers. However, surveys on the phytoplankton-associated bacterial communities, pivotal to ecosystem functioning in Arctic fjords, are limited. This study investigated the interactions between phytoplankton and heterotrophic bacterial communities in Svalbard fjord waters through comprehensive eDNA metabarcoding with 16S and 18S rRNA genes. The 16S rRNA sequencing results revealed a homogenous community composition including a few dominant heterotrophic bacteria across fjord waters, whereas 18S rRNA results suggested a spatially diverse eukaryotic plankton distribution. The relative abundances of heterotrophic bacteria showed a depth-wise distribution. By contrast, the dominant phytoplankton populations exhibited variable distributions in surface waters. In the network model, the linkage of phytoplankton (Prasinophytae and Dinophyceae) to heterotrophic bacteria, particularly Actinobacteria, suggested the direct or indirect influence of bacterial contributions on the fate of phytoplankton-derived organic matter. Our prediction of the metabolic pathways for bacterial activity related to phytoplankton-derived organic matter suggested competitive advantages and symbiotic relationships between phytoplankton and heterotrophic bacteria. Our findings provide valuable insights into the response of phytoplankton-bacterial interactions to environmental changes in Arctic fjords.

European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events.

BACKGROUND: A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. METHODS AND RESULTS: Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals. CONCLUSIONS: CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

Nondestructive Single-Atom-Thick Crystallographic Scanner via Sticky-Note-Like van der Waals Assembling-Disassembling.

Crystallographic characteristics, including grain boundaries and crystallographic orientation of each grain, are crucial in defining the properties of two-dimensional materials (2DMs). To date, local microstructure analysis of 2DMs, which requires destructive and complex processes, is primarily used to identify unknown 2DM specimens, hindering the subsequent use of characterized samples. Here, a nondestructive large-area 2D crystallographic analytical method through sticky-note-like van der Waals (vdW) assembling-disassembling is presented. By the vdW assembling of veiled polycrystalline graphene (PCG) with a single-atom-thick single-crystalline graphene filter (SCG-filter), detailed crystallographic information of each grain in PCGs is visualized through a 2D Raman signal scan, which relies on the interlayer twist angle. The scanned PCGs are seamlessly separated from the SCG-filter using vdW disassembling, preserving their original condition. The remaining SCG-filter is then reused for additional crystallographic scans of other PCGs. It is believed that the methods can pave the way for advances in the crystallographic analysis of single-atom-thick materials, offering huge implications for the applications of 2DMs.

The Effects of Radiofrequency Catheter Ablation for Atrial Fibrillation on Right Ventricular Function.

BACKGROUND AND OBJECTIVE: The effects of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) on right ventricular (RV) function are not well known. METHODS: Patients who underwent RFCA for AF and underwent pre- and post-procedural echocardiography were enrolled consecutively. Fractional area change (FAC), RV free-wall longitudinal strain (RVFWSL), and RV 4-chamber strain including the ventricular septum (RV4CSL) were measured. Changes in FAC, RVFWSL, and RV4CSL before and after RFCA were compared among paroxysmal AF (PAF), persistent AF (PeAF), and long-standing persistent AF (LSPeAF) groups. RESULTS: A total of 164 participants (74 PAF, 47 PeAF, and 43 LSPeAF; age, 60.8 ± 9.8 years; men, 74.4%) was enrolled. The patients with PeAF and LSPeAF had worse RV4CSL (p<0.001) and RVFWSL (p<0.001) than those with PAF and reference values. Improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared with the PAF and LSPeAF groups (ΔRV4CSL, 8.4% [5.1, 11.6] in PeAF vs. 1.0% [-1.0, 4.1] in PAF, 1.9% [-0.2, 4.4] in LSPeAF, p<0.001; ΔRVFWSL, 9.0% [6.9, 11.5] in PeAF vs. 0.9% [-1.4, 4.9] in PAF, 1.0% [-1.0, 3.6] in LSPeAF, p<0.001). In patients without recurrence, improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared to the LSPeAF group. CONCLUSIONS: RV systolic function is more impaired in patients with PeAF and LSPeAF than in those with PAF. RV systolic function is more improved after RFCA in patients with PeAF than in those with PAF or LSPeAF.

Intrinsic signal optoretinography of dark adaptation abnormality due to rod photoreceptor degeneration.

This research aims to investigate the potential of using intrinsic optical signal (IOS) optoretinography (ORG) to objectively detect dark adaptation (DA) abnormalities related to rod photoreceptor degeneration. Functional optical coherence tomography (OCT) was employed in both wild-type (WT) and retinal degeneration 10 (rd10) mice to conduct this assessment. Dynamic OCT measurements captured the changes in retinal thickness and reflectance from light-to-dark transition. Comparative analysis revealed significant IOS alterations within the outer retina. Specifically, a reduction in thickness from external limiting membrane (ELM) peak to retinal pigment epithelium (RPE) peak was observed (WT: 1.13 ± 0.69 µm, 30 min DA; rd10: 2.64 ± 0.86 µm, 30 min DA), as well as a decrease in the intensity of the inner segment ellipsoid zone (EZ) in 30 min DA compared to light adaptation (LA). The reduction of relative EZ intensity was notable in rd10 after 5 min DA and in WT after 15 min DA, with a distinguishable difference between rd10 and WT after 10 min DA. Furthermore, our findings indicated a significant decrease in the relative intensity of the hypo-reflective band between EZ and RPE in rd10 retinas during DA, which primarily corresponds to the outer segment (OS) region. In conclusion, the observed DA-IOS abnormalities, including changes in ELM-RPE thickness, EZ, and OS intensity, hold promise as differentiators between WT and rd10 mice before noticeable morphological abnormalities occur. These findings suggest the potential of this non-invasive imaging technique for the early detection of dysfunction in retinal photoreceptors.

Durvalumab Consolidation After Chemoradiotherapy in Elderly Patients With Unresectable Stage III NSCLC: A Real-World Multicenter Study.

BACKGROUND: The PACIFIC trial demonstrated survival benefit of durvalumab after concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small-cell lung cancer. Data on the effectiveness and safety of durvalumab in elderly patients is lacking. METHODS: This retrospective study was conducted between September 2017 and September 2022. Progression-free survival (PFS), overall survival (OS), recurrence patterns, first subsequent treatment after recurrence, factors associated with survival outcomes, and adverse events (AEs) were compared. RESULTS: Of the 286 patients, 120 (42.0%) were ≥ 70 years and 166 (58.0%) were < 70 years. The median PFS (17.7 vs. 19.4 months; P = .43) and median OS (35.7 months vs. not reached; P = .13) were similar between 2 groups. Proportion of patients who completed durvalumab was lower in elderly patients (27.5% vs. 39.2%; P = .040). In elderly patients, ECOG PS 0 or 1 was associated with better PFS, and being male and having received a cisplatin-based regimen during CCRT were factors associated with better and worse OS, respectively. In patients aged < 70 years, a PD-L1 ≥ 50% was associated with improved PFS and OS. Elderly patients experienced more treatment-related AEs, grade 3/4 AEs, permanent discontinuation of durvalumab, and treatment-related deaths. Among the AEs leading to permanent discontinuation or death, pulmonary AE was significantly more common in elderly patients. CONCLUSION: Durvalumab demonstrated similar outcomes in elderly compared to younger patients. However, AEs were more common in elderly patients. Thus, judicious selection of patients and chemotherapy regimens, coupled with careful AE monitoring, are important factors for ensuring optimal durvalumab treatment.

Defect engineered ternary metal spinel-type Ni-Fe-Co oxide as bifunctional electrocatalyst for overall electrochemical water splitting.

Transition metal spinel oxides were engineered with active elements as bifunctional water splitting electrocatalysts to deliver superior intrinsic activity, stability, and improved conductivity to support green hydrogen production. In this study, we reported the ternary metal Ni-Fe-Co spinel oxide electrocatalysts prepared by defect engineering strategy with rich and deficient Na+ ions, termed NFCO-Na and NFCO, which suggest the formation of defects with Na+ forming tensile strain. The Na-rich NiFeCoO4 spinel oxide reveals lattice expansion, resulting in the formation of a defective crystal structure, suggesting higher electrocatalytic active sites. The spherical NFCO-Na electrocatalysts exhibit lower OER and HER overpotentials of 248 mV and 153 mV at 10 mA cm-2 and smaller Tafel slope values of about 78 mV dec-1 and 129 mV dec-1, respectively. Notably, the bifunctional NFCO-Na electrocatalyst requires a minimum cell voltage of about 1.67 V to drive a current density of 10 mA cm-2. The present work highlights the significant electrochemical activity of defect-engineered ternary metal oxides, which can be further upgraded as highly active electrocatalysts for water splitting applications.

Anti- and pro-fibrillatory effects of pulmonary vein isolation gaps in human atrial fibrillation digital twins.

Although pulmonary vein isolation (PVI) gaps and extrapulmonary vein triggers contribute to recurrence after atrial fibrillation (AF) ablation, their precise mechanisms remain unproven. Our study assessed the impact of PVI gaps on rhythm outcomes using a human AF digital twin. We included 50 patients (76.0% with persistent AF) who underwent catheter ablation with a realistic AF digital twin by integrating computed tomography and electroanatomical mapping. We evaluated the final rhythm status, including AF and atrial tachycardia (AT), across 600 AF episodes, considering factors including PVI level, PVI gap number, and pacing locations. Our findings revealed that antral PVI had a significantly lower ratio of AF at the final rhythm (28% vs. 56%, p = 0.002) than ostial PVI. Increasing PVI gap numbers correlated with an increased ratio of AF at the final rhythm (p < 0.001). Extra-PV induction yielded a higher ratio of AF at the final rhythm than internal PV induction (77.5% vs. 59.0%, p < 0.001). In conclusion, our human AF digital twin model helped assess AF maintenance mechanisms. Clinical trial registration: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695.

Racial Differences in Bleeding Risk: An Ecological Epidemiological Study Comparing Korea and United Kingdom Subjects.

BACKGROUND: This study aimed to evaluate racial differences in bleeding incidence by conducting an ecological epidemiological study using data from Korea and the United Kingdom. METHODS: We included healthy participants from the Korean National Health Insurance Service-Health Screening and the UK Biobank who underwent health examinations between 2006 and 2010 and had no comorbidities or history of medication use. Finally, 112,750 East Asians (50.7% men, mean age 52.6 years) and 210,995 Caucasians (44.7% men, mean age 55.0 years) were analyzed. The primary outcome was composed of intracranial hemorrhage (ICH) and bleeding from the gastrointestinal, respiratory, and genitourinary systems. RESULTS: During the follow-up, primary outcome events occurred in 2,110 East Asians and in 6,515 Caucasians. East Asians had a 38% lower 5-year incidence rate compared with Caucasians (3.88 vs. 6.29 per 1,000 person-years; incidence rate ratio [IRR]: 0.62, 95% confidence interval [CI]: 0.59-0.65). East Asians showed a lower incidence of major bleeding (IRR: 0.86, 95% CI: 0.81-0.91), bleeding from the gastrointestinal (IRR: 0.53, 95% CI: 0.49-0.56), and genitourinary systems (IRR: 0.49, 95% CI: 0.44-0.53) compared with Caucasians. The incidence rates of ICH (IRR: 3.20, 95% CI: 2.67-3.84) and bleeding from the respiratory system (IRR: 1.28, 95% CI: 1.11-1.47) were higher in East Asians. Notably, East Asians consuming alcohol ≥3 times/week showed a higher incidence of the primary outcome than Caucasians (IRR: 1.12, 95% CI: 1.01-1.25). CONCLUSION: This ecological study revealed significant racial differences in bleeding incidence, influenced by anatomical sites and lifestyle habits, underscoring the need for tailored approaches in bleeding management based on race.

Development and validation of cardiac diffusion weighted magnetic resonance imaging for the diagnosis of myocardial injury in small animal models.

Cardiac diffusion weighted-magnetic resonance imaging (DWI) has slowly developed due to its technical difficulties. However, this limitation could be overcome by advanced techniques, including a stimulated echo technique and a gradient moment nulling technique. This study aimed to develop and validate a high-order DWI sequence, using echo-planar imaging (EPI) and second-order motion-compensated (M012) diffusion gradient applied to cardiac imaging in small-sized animals with fast heart and respiratory rates, and to investigate the feasibility of cardiac DWI, diagnosing acute myocardial injury in isoproterenol-induced myocardial injury rat models. The M012 diffusion gradient sequence was designed for diffusion tensor imaging of the rat myocardium and validated in the polyvinylpyrrolidone phantom. Following sequence optimization, 23 rats with isoproterenol-induced acute myocardial injury and five healthy control rats underwent cardiac MRI, including cine imaging, T1 mapping, and DWI. Diffusion gradient was applied using a 9.4-T MRI scanner (Bruker, BioSpec 94/20, gradient amplitude = 440 mT/m, maximum slew rate = 3440 T/m/s) with double gating (electrocardiogram and respiratory gating). Troponin I was used as a serum biomarker for myocardial injury. Histopathologic examination of the heart was subsequently performed. The developed DWI sequence using EPI and M012 provided the interpretable images of rat hearts. The apparent diffusion coefficient (ADC) values were significantly higher in rats with acute myocardial injury than in the control group (1.847 ± 0.326 * 10-3 mm2/s vs. 1.578 ± 0.144 * 10-3 mm2/s, P < 0.001). Troponin I levels were increased in the blood samples of rats with acute myocardial injury (P < 0.001). Histopathologic examinations detected myocardial damage and subendocardial fibrosis in rats with acute myocardial injury. The newly developed DWI technique has the ability to detect myocardial injury in small animal models, representing high ADC values on the myocardium with isoproterenol-induced injury.

Identification of Hit Compounds Using Artificial Intelligence for the Management of Allergic Diseases.

This study aimed to identify and evaluate drug candidates targeting the kinase inhibitory region of suppressor of cytokine signaling (SOCS) 3 for the treatment of allergic rhinitis (AR). Utilizing an artificial intelligence (AI)-based new drug development platform, virtual screening was conducted to identify compounds inhibiting the SH2 domain binding of SOCS3. Luminescence assays assessed the ability of these compounds to restore JAK-2 activity diminished by SOCS3. Jurkat T and BEAS-2B cells were utilized to investigate changes in SOCS3 and STAT3 expression, along with STAT3 phosphorylation in response to the identified compounds. In an OVA-induced allergic rhinitis mouse model, we measured serum levels of total IgE and OVA-specific IgE, performed real-time PCR on nasal mucosa samples to quantify Th2 cytokines and IFN-γ expression, and conducted immunohistochemistry to analyze eosinophil levels. Screening identified 20 hit compounds with robust binding affinities. As the concentration of SOCS3 increased, a corresponding decrease in JAK2 activity was observed. Compounds 5 and 8 exhibited significant efficacy in restoring JAK2 activity without toxicity. Treatment with these compounds resulted in reduced SOCS3 expression and the reinstatement of STAT3 phosphorylation in Jurkat T and BEAS-2B cells. In the OVA-induced allergic rhinitis mouse model, compounds 5 and 8 effectively alleviated nasal symptoms and demonstrated lower levels of immune markers compared to the allergy group. This study underscores the promising nonclinical efficacy of compounds identified through the AI-based drug development platform. These findings introduce innovative strategies for the treatment of AR and highlight the potential therapeutic value of targeting SOCS3 in managing AR.