Predictive Factors of Apparent Treatment Resistant Hypertension Among Patients With Hypertension Identified Using Electronic Health Records.

BACKGROUND: Early identification of a patient with resistant hypertension (RH) enables quickly intensified treatment, short-interval follow-up, or perhaps case management to bring his or her blood pressure under control and reduce the risk of complications. OBJECTIVE: To identify predictors of RH among individuals with newly diagnosed hypertension (HTN), while comparing different prediction models and techniques for managing missing covariates using electronic health records data. DESIGN: Risk prediction study in a retrospective cohort. PARTICIPANTS: Adult patients with incident HTN treated in any of the primary care clinics of one health system between April 2013 and December 2016. MAIN MEASURES: Predicted risk of RH at the time of HTN identification and candidate predictors for variable selection in future model development. KEY RESULTS: Among 26,953 individuals with incident HTN, 613 (2.3%) met criteria for RH after 4.7 months (interquartile range, 1.2-11.3). Variables selected by the least absolute shrinkage and selection operator (LASSO), included baseline systolic blood pressure (SBP) and its missing indicator (a dummy variable created if baseline SBP is absent), use of antihypertensive medication at the time of cohort entry, body mass index, and atherosclerosis risk. The random forest technique achieved the highest area under the curve (AUC) of 0.893 (95% CI, 0.881-0.904) and the best calibration with a calibration slope of 1.01. Complete case analysis is not a valuable option (AUC = 0.625). CONCLUSIONS: Machine learning techniques and traditional logistic regression exhibited comparable levels of predictive performance after handling the missingness. We suggest that the variables identified by this study may be good candidates for clinical prediction models to alert clinicians to the need for short-interval follow up and more intensive early therapy for HTN.

REM sleep without atonia and neurocognitive function in isolated REM sleep behaviour disorder: Cross-sectional and longitudinal study.

This study investigated the relationship between rapid eye movement sleep without atonia and cognitive profiles in individuals diagnosed with isolated rapid eye movement sleep behaviour disorder, assesssing both cross-sectional associations and their link to phenoconversion in a longitudinal follow-up. Participants underwent video-polysomnography, neurological examination, neuropsychological tests and structured interviews to confirm isolated rapid eye movement sleep behaviour disorder. Rapid eye movement sleep without atonia was manually scored using the Montreal method, and participants were categorized into either high or low electromyography activity groups, based on their tonic and phasic electromyography activities. The cross-sectional study included 250 patients with isolated rapid eye movement sleep behaviour disorder, revealing that those with high tonic electromyography activity exhibited significantly lower scores in the constructional praxis recall than those with low tonic electromyography activity (p = 0.002). In the longitudinal study, 79 participants (63 isolated rapid eye movement sleep behaviour disorder and 16 phenoconversion), tracked for at least 5 years, demonstrated that high tonic electromyography activity (odds ratio: 6.14; 95% confidence interval: 1.23-30.60; p = 0.027) and lower performance on the Trail Making Test A (odds ratio: 0.23; 95% confidence interval: 0.11-0.70; p = 0.007) were associated with future phenoconversion. These results confirm the link between tonic electromyography activity and neurodegeneration in isolated rapid eye movement sleep behaviour disorder. Combining rapid eye movement sleep without atonia assessment with cognitive evaluation could serve as an early predictive marker for phenoconversion in clinical settings.

Depth-Resolved X-Ray Photoelectron Spectroscopy Evidence of Intrinsic Polar States in HfO2-Based Ferroelectrics.

The discovery of ferroelectricity in nanoscale hafnia-based oxide films has spurred interest in understanding their emergent properties. Investigation focuses on the size-dependent polarization behavior, which is sensitive to content and movement of oxygen vacancies. Though polarization switching and electrochemical reactions is shown to co-occur, their relationship remains unclear. This study employs X-ray photoelectron spectroscopy with depth sensitivity to examine changes in electrochemical states occurring during polarization switching. Contrasting Hf0.5Zr0.5O2 (HZO) with Hf0.88La0.04Ta0.08O2 (HLTO), a composition with an equivalent structure and comparable average ionic radius, electrochemical states are directly observed for specific polarization directions. Lower-polarization films exhibit more significant electrochemical changes upon switching, suggesting an indirect relationship between polarization and electrochemical state. This research illuminates the complex interplay between polarization and electrochemical dynamics, providing evidence for intrinsic polar states in HfO2-based ferroelectrics.

Image-based ECG analyzing deep-learning algorithm to predict biological age and mortality risks: interethnic validation.

BACKGROUND: Cardiovascular risk assessment is a critical component of healthcare, guiding preventive and therapeutic strategies. In this study, we developed and evaluated an image-based electrocardiogram (ECG) analyzing an artificial intelligence (AI) model that estimates biological age and mortality risk. METHODS: Using a dataset of 978 319 ECGs from 250 145 patients at Seoul National University Bundang Hospital, we developed a deep-learning model utilizing printed 12-lead ECG images to estimate patients' age (ECG-Age) and 1- and 5-year mortality risks. The model was validated externally using the CODE-15% dataset from Brazil. RESULTS: The ECG-Age showed a high correlation with chronological age in both the internal and external validation datasets (Pearson's R = 0.888 and 0.852, respectively). In the internal validation, the direct mortality risk prediction models showed area under the curves (AUCs) of 0.843 and 0.867 for 5- and 1-year all-cause mortality, respectively. For 5- and 1-year cardiovascular mortality, the AUCs were 0.920 and 0.916, respectively. In the CODE-15%, the mortality risk predictions showed AUCs of 0.818 and 0.836 for the prediction of 5- and 1-year all-cause mortality, respectively. Compared to the neutral Delta-Age (ECG-Age - chronological age) group, hazard ratios for deaths were 1.88 [95% confidence interval (CI): 1.14-3.92], 2.12 (95% CI: 1.15-3.92), 4.46 (95% CI: 2.22-8.96) and 7.68 (95% CI: 3.32-17.76) for positive Delta-Age groups (5-10, 10-15, 15-20, >20), respectively. CONCLUSION: An image-based AI-ECG model is a feasible tool for estimating biological age and assessing all-cause and cardiovascular mortality risks, providing a practical approach for utilizing standardized ECG images in predicting long-term health outcomes.

Bilaterally positive head-impulse tests can differentiate AICA infarction from labyrinthitis.

Introduction: Video head-impulse tests (video-HITs) often fail to detect anterior inferior cerebellar artery (AICA) infarction due to peripheral and central vestibular system involvement. Anecdotal studies suggest that video-HITs may reveal bilateral impairment in AICA infarction. However, the diagnostic utility of video-HITs has not been established, particularly when compared to labyrinthitis, which accounts for the majority of acute audiovestibular syndrome (AAVS) cases. Methods: We reviewed the medical records of consecutive patients presenting with new-onset acute hearing loss and spontaneous vertigo (i.e., AAVS) between March 2018 and July 2023 at a tertiary hospital in South Korea. Video-HIT patterns were categorized as follows: (1) ipsilaterally positive, (2) contralaterally positive, (3) bilaterally normal, and (4) bilaterally positive. Results: Twenty-eight patients with AICA infarction (mean age ± standard deviation = 67 ± 15 years; 14 men) and 51 with labyrinthitis (63 ± 17 years, 26 men) were included in the analyses. Among the 28 patients with AICA infarction, 15 presented with AAVS in isolation, without other co-morbid neurologic deficits (15/28, 54%). The vestibulo-ocular reflex (VOR) gains of ipsilesional horizontal canals (HCs) ranged from 0.21 to 1.22 (median = 0.81, interquartile range [IQR] = 0.50-0.89). However, those for contralateral HC gain ranged from 0.57 to 1.19 (median = 0.89 [IQR = 0.73-0.97]). Collectively, HITs were bilaterally positive in 13 patients (including 12 patients with bilaterally positive HITs for the horizontal canal), normal in eight, ipsilesionally positive in six, and contralesionally positive in one patient with AICA infarction. The VOR gains were typically decreased ipsilaterally in 28 (28/51, 55%), normal in 17 (17/51, 33%), and decreased bilaterally in six patients with labyrinthitis (6/51, 12%). Logistic regression analysis revealed that bilaterally positive HITs (p = 0.004) and multiple vascular risk factors (p = 0.043) were more frequently associated with AICA infarction than labyrinthitis. Discussion: Among patients presenting with AAVS, bilaterally positive HITs can be indicative of AICA infarction in patients with multiple vascular risk factors.

Causal inference using multivariate generalized linear mixed-effects models.

Dynamic prediction of causal effects under different treatment regimens is an essential problem in precision medicine. It is challenging because the actual mechanisms of treatment assignment and effects are unknown in observational studies. We propose a multivariate generalized linear mixed-effects model and a Bayesian g-computation algorithm to calculate the posterior distribution of subgroup-specific intervention benefits of dynamic treatment regimes. Unmeasured time-invariant factors are included as subject-specific random effects in the assumed joint distribution of outcomes, time-varying confounders, and treatment assignments. We identify a sequential ignorability assumption conditional on treatment assignment heterogeneity, that is, analogous to balancing the latent treatment preference due to unmeasured time-invariant factors. We present a simulation study to assess the proposed method's performance. The method is applied to observational clinical data to investigate the efficacy of continuously using mycophenolate in different subgroups of scleroderma patients.

Reduced aggregation of the Leghorn Male Hepatoma (LMH) cell line in suspension by supplementing dextran sulfate in the media.

Objective: The study aimed to improve the efficiency of Leghorn Male Hepatoma (LMH) cells for animal virus vaccine production by transitioning from adherent to suspension culture and evaluating the effects of dextran sulfate (DS) on preventing cell aggregation. The goal was to enhance cell growth, viability, and glucose metabolism and to develop efficient suspension-adapted LMH cells for large-scale vaccine production. Methods: LMH cells previously cultured in an adherent state were transferred to 125 mL Erlenmeyer flasks to conduct suspension culture. Cell culture performance, including cell density, viability, and glucose metabolism, during the cultures was measured, along with an assessment of cell aggregation. Additionally, mRNA expression levels of genes associated with cell adhesion and apoptosis were monitored. Results: DS supplementation in suspension culture enhanced cell viability and growth, with higher cell densities and viabilities compared to control media. Additionally, DS supplementation reduced glucose consumption and waste production, indicating improved metabolic efficiency. DS also delayed cell aggregation, possibly by downregulating integrin expression and promoting anti-apoptotic gene expression. However, even after 2 months, cell aggregation persisted in both control and DS-supplemented cultures, suggesting further optimization is needed for LMH cell adaptation to suspension culture. Conclusion: DS supplementation in LMH cell suspension cultures led to notable improvements in cell growth, viability, and glucose metabolism, while also decreasing the cell aggregation.

Association between antibiotics use and osteoporotic fracture risk: a nationally representative retrospective cohort study.

This population-based retrospective cohort study aimed to estimate the association between antibiotic exposure and osteoporotic fracture risk. Long-term antibiotic use was associated with the risk of osteoporotic fracture. An increase in the number of antibiotic classes prescribed may also be associated with an increased osteoporotic fracture risk. PURPOSE: This study aims to examine the association between antibiotic usage and osteoporotic fractures in a large cohort of Korean adults, with a specific focus on the duration of antibiotic exposure and the number of antibiotic classes used. METHODS: This retrospective cohort study from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from January 1, 2002, to December 31, 2019, included 167,370 Korean adults aged 50 years or older (mean [SD] age, 59.3 [7.82] years; 65,425 [39.09%] women). The cumulative antibiotic prescription days and the classes of antibiotics prescribed between 2004 and 2008 were exposure variables, respectively. The main outcome was a newly diagnosed osteoporotic fracture during follow-up. Cox proportional hazard regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident osteoporotic fractures associated with antibiotic exposure. RESULTS: The antibiotic user group with 91 days had a higher risk of osteoporotic fracture in comparison to the antibiotic non-user group (aHR, 1.12; 95% CI, 1.03-1.21). Additionally, those who used more than four different antibiotic classes had an elevated risk of osteoporotic fracture compared to the non-user group (aHR, 1.10; 95% CI, 1.02-1.18). CONCLUSION: This extensive population-based cohort study conducted on a large population has identified an association between the utilization of antibiotics and an elevated risk of osteoporotic fractures. The cumulative days exposed to antibiotics and osteoporotic fractures may be positively associated.

Ocular vestibular-evoked myogenic potential assists in differentiation of multiple system atrophy from Parkinson's disease.

Vestibular-evoked myogenic potentials (VEMPs) can help assess otolithic neural pathway in the brainstem that may also participate in cardiovascular autonomic function. Parkinson's disease (PD) is associated with altered VEMP responses; however, the association between VEMP abnormalities and multiple system atrophy (MSA) remains unknown. Therefore, we compared the extent of otolith dysfunction using ocular (oVEMP) and cervical VEMP (cVEMP) between MSA and PD. We analyzed the clinical features and VEMP and head-up tilt table test (HUT) findings using the Finometer in 24 patients with MSA and 52 with de-novo PD, who had undergone neurotologic evaluation in a referral-based university hospital in South Korea from January 2021 to March 2023. MSA was associated with bilateral oVEMP abnormality (odds ratio [95% confidence interval] = 9.19 [1.77-47.76], p=0.008). n1-p1 amplitude was negatively correlated with Unified Multiple System Atrophy Rating Scale I-II scores in patients with MSA (r=-0.571, p=0.033), whereas it did not correlate with Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III scores in patients with PD (r=-0.051, p=0.687). n1 latency was negatively correlated with maximum changes in systolic blood pressure within 15 s during HUT in patients with PD (r=-0.335, p=0.040) but not in those with MSA (r=0.277, p=0.299). In conclusion, bilaterally abnormal oVEMP responses may indicate the extent of brainstem dysfunction in MSA. oVEMP reflects the integrity of otolith-autonomic interplay, reliably assists in differentiating between MSA and PD, and helps infer clinical decline.

Healthcare Costs due to Dizziness/Vertigo in Korea: Analyses Using the Public Data of Health Insurance Review & Assessment Service.

BACKGROUND: Dizziness/vertigo is one of the most common symptoms for which people seek healthcare. However, the healthcare expenditure attributable to dizziness/vertigo in South Korea remains poorly understood. We investigated the healthcare costs due to six major disorders causing dizziness/vertigo using claims data. METHODS: The healthcare costs were evaluated using all the claims data submitted to the Health Insurance Review and Assessment Service from January 1 to December 31, 2022. The six major vestibular disorders included for analysis were benign paroxysmal positional vertigo (BPPV), psychogenic/persistent postural perceptual dizziness (PPPD), vascular vertigo/dizziness (VVD), vestibular migraine (VM), Meniere's disease (MD), and vestibular neuritis (VN). RESULTS: During the 1-year study period, 4.1% of adults aged 20 or older visited hospitals due to dizziness/vertigo in South Korea. Compared to the general population, the patients with dizziness/vertigo were more often elderly, female, and residents of small towns. The total healthcare cost for the six major vestibular disorders was ₩547.8 billion (approximately $406.5 million). BPPV incurred the highest annual healthcare cost (₩183.5 billion, 33.5%), followed by VVD (₩158.8 billion, 29.0%), MD (₩82.2 billion, 15.0%), psychogenic/PPPD (₩60.3 billion, 11.0%), VN (₩32.9 billion, 6.0%), and VM (₩30.1 billion, 5.5%). The mean healthcare cost per hospital visit due to dizziness/vertigo was ₩96,524 (95% confidence interval, ₩96,194-₩96,855), 30% higher than the average (₩73,948) of the overall healthcare cost per hospital visit over the same period. CONCLUSION: Owing to higher healthcare costs for dizziness/vertigo and increased prevalence of dizziness/vertigo in the aged population, healthcare costs due to dizziness/vertigo will increase rapidly in South Korea. Thus, a guideline for cost-effective management of dizziness/vertigo should be established to reduce the healthcare costs due to these common symptoms.

Fucoidan refined from Saccharina japonica ameliorates ambient particulate matter-induced inflammation in keratinocytes, underlying fibroblasts, and 12-O-tetradecanoylphorbol 13-acetate-induced ear edema in mice.

Fucoidan from Saccharina japonica (SJF) was isolated and characterized, and its anti-inflammatory effects on fine dust/ambient particulate matter (PM)-stimulated HaCaT keratinocytes were investigated. SJF increased cell viability by reducing intracellular ROS production in PM-stimulated HaCaT keratinocytes. Moreover, SJF downregulated the expression/production of inflammatory cytokines (IL-6, IL-8, IL-13, IL-25, IL-33, TNF-α, IFN-γ, and TSLP) and chemokines (MDC and TARC) through modulating NF-κB/MAPK signaling in PM-stimulated HaCaT keratinocytes. Extended studies investigated the impact of SJF-treated HaCaT keratinocyte culture media on HDFs. Interestingly, media from SJF-treated HaCaT keratinocytes on HDFs demonstrated a notable downregulation of the production of inflammatory mediators such as TSLP, IL-6, IL-8, IL-13, and TNF-α, as well as TARC and MDC. Furthermore, the study examined the impact of SJF on 12-O-tetradecanoylphorbol 13-acetate (TPA) induced ear edema in BALB/c mice and results indicated the reduced ear thickness and decreased iNOS and COX-2 expression. Our study confirmed the effectiveness of SJF in ameliorating PM-induced skin inflammation in in vitro experiments, along with the TPA-induced in vivo inflammatory model.

Association of changes in predicted body composition with subsequent risk of dementia.

OBJECTIVE: The effect of body composition change on the risk of dementia is not clear. This study analyzed the associations of changes in predicted lean body mass index (pLBMI), predicted appendicular skeletal muscle mass index (pASMI), and predicted body fat mass index (pBFMI) with the risk of dementia. METHODS: In this nationwide cohort study, data were obtained from the Korean National Health Insurance Service database. The exposure was defined as changes in pLBMI, pASMI, and pBFMI derived from validated prediction equations. The outcome was dementia, defined based on the dementia diagnosis with prescription of anti-dementia medication. Cox proportional hazards regression analyses were performed to obtain the hazard ratio with a 95% confidence interval for risk of dementia according to changes in predicted body composition. RESULTS: A total of 13,215,208 individuals with no prior record of dementia who underwent health screenings twice between 2009-2010 and 2011-2012 were included. A 1-kg/m2 increase in pLBMI and pASMI had an association with reduced risk of dementia (aHR: 0.85, 95% CI 0.84-0.87; aHR: 0.70, 95% CI 0.69-0.72, respectively for men, and aHR: 0.69, 95% CI 0.67-0.71; aHR: 0.59, 95% CI 0.57-0.61, respectively for women). A 1-kg/m2 increase in pBFMI had an association with a raised risk of dementia (aHR: 1.19, 95% CI 1.17-1.21 for men and aHR: 1.53, 95% CI 1.48-1.57 for women). These results remained consistent regardless of sex or weight change. INTERPRETATION: Increase in pLBMI or pASMI, or reduction in pBFMI was linked to lower risk of dementia.

Experimental Analysis of Robotic Cortical Bone Specimen Drilling Performance: Effect of Cryogen.

In orthopedic surgery, precise bone screw insertion is crucial for stabilizing fractures, necessitating a preliminary cortical bone drilling procedure. However, this process can induce temperatures exceeding 70 °C due to the low thermal conductivity of cortical bone, potentially leading to thermal osteonecrosis. Furthermore, significant cutting forces and torque pose risks of tool breakage and bone damage, underlining the need for high precision and optimal processing parameters. Traditionally, drilling relies on the surgeon's experience and often results in imprecise outcomes due to inconsistent feed rates. Therefore, this study proposes the use of a 6-axis robot for controlled drilling, offering precise control over angular velocities and consistent feed rates. Additionally, explore the use of cryogenic liquid nitrogen (LN2) as a novel cooling method compared to conventional saline solutions, examining its efficacy under various cutting conditions. The results demonstrate that LN2 cooling conditions lead to a reduction in thrust and torque under specific processing conditions, and facilitate smoother chip evacuation. Additionally, LN2 significantly lowers the peak temperature around the drilling site, thus minimizing the risk of thermal osteonecrosis. Consequently, the use of a 6-axis robot provides consistent feed rates, and LN2 cooling achieves optimal processing conditions, enabling a more controlled and effective drilling process.

Racial variability in immune responses only partially explains differential systemic sclerosis disease severity.

OBJECTIVE: To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients. METHODS: 803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (ACA), RNA-polymerase III (POLR3), Scl70, PM/Scl, NOR90, Th/To, Ku, U3RNP and Ro52) and commercial ELISA (U1RNP). In this observational study, logistic regression was performed to assess the association between self-identified race and outcomes, adjusting for autoantibodies. To estimate whether the effect of race was mediated by autoantibody status, race coefficients from multivariate models including and excluding autoantibodies were compared. RESULTS: Anti-Scl70, anti-U1RNP, anti-U3RNP, anti-Th/To, anti-Ku and anti-NOR90 were more common in the black cohort than in the white cohort, which was enriched for ACA, anti-POLR3 and anti-PM/Scl. Black individuals had a higher prevalence of severe Raynaud's, skin, lung, gastrointestinal and renal disease whereas white individuals had a higher prevalence of severe heart and muscle disease. Adjusting for autoantibodies decreased the effect of race on outcome for telangiectasias, forced vital capacity <70%, pulmonary hypertension and severe lung, heart, muscle and gastrointestinal disease by 11%-44% and increased the association between race and renal crisis and severe kidney disease by 37%-52%. CONCLUSIONS: This study is the largest systematic analysis of autoantibody responses in a geographically diverse population of black SSc patients. Black and white individuals with SSc have distinct autoantibody profiles. Autoantibodies explain only a fraction of the effect of race on clinical outcomes, suggesting other factors contribute to disparate outcomes between these groups.

Heterogeneous Acrylic Resins with Bicontinuous Nanodomains as Low-Modulus Flexible Adhesives.

Adhesives play a critical role in the assembly of electronic devices, particularly as devices become more diverse in form factors. Flexible displays require highly transparent and rapidly recoverable adhesives with a certain stiffness. In this study, novel structured adhesives are developed that incorporate bicontinuous nanodomains to fabricate flexible adhesives with low moduli. This structure is obtained via polymerization-induced microphase separation using a macro chain transfer agent (CTA). Phase separation is characterized using small-angle X-ray scattering, transmission electron microscopy, and dynamic mechanical analysis. By optimizing the length of the macro CTA, an adhesive with both hard and soft nanodomains is produced, resulting in exceptional flexibility (strain recovery = 93%) and minimal modulus (maximum stress/applied strain = 7 kPa), which overperforms traditional adhesives. The optimized adhesive exhibits excellent resilience under extensive strain, as well as strong adhesion and transparency. Furthermore, dynamic folding tests demonstrate the exceptional stability of the adhesive under various temperature and humidity conditions, which is attributed to its unique structure. In summary, the distinct bicontinuous phase structure confers excellent transparency, flexibility, and reduced stiffness to the adhesive, rendering it well-suited for commercial foldable displays and suggesting potential applications in stretchable displays and wearable electronics.