Association between types of antihypertensive medication and the risk of atrial fibrillation: a nationwide population study.

Background: Patients with hypertension are at a high risk of atrial fibrillation (AF). Recent research has indicated the varying effects of antihypertensive medications on developing AF. Objectives: We investigated the relationship between different types of antihypertensive medications and the risk of AF occurrence. Methods: We analyzed data from 113,582 subjects with national health screening examinations between 2009 and 2014. The study population was categorized according to antihypertensive medication type. The primary outcome was the incidence of AF. Results: Among 113,582 subjects (mean age 59.4 ± 12.0 years, 46.7% men), 93,557 received monotherapy [angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), beta-blockers, calcium channel blockers (CCB), or diuretics], while 34,590 received combination therapy (ARB/beta-blockers, ARB/CCB, ARB/diuretics, or ARB/CCB/diuretics). During a mean follow-up duration of 7.6 ± 2.1 years, 3.9% of patients were newly diagnosed with AF. In monotherapy, ACEi and CCB had similar AF risks as ARB, while beta-blockers and diuretics showed higher AF risks than ARB. In combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers had the highest compared to ARB/CCB. Among the specific ARBs, the AF risk varied insignificantly, except for telmisartan and candesartan. Conclusions: In hypertensive patients receiving monotherapy, ACEi and CCB showed a similar AF risk as ARBs, while beta-blockers and diuretics were associated with a higher risk. Among those receiving combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers showed the highest risk. Various types of ARBs have different associations with AF risk.

Alcohol is neither a risk factor nor a protective factor for sudden cardiac death and/or fatal ventricular arrhythmia: A population-based study with genetic traits and alcohol consumption in the UK Biobank.

BACKGROUND: The association between alcohol consumption and the risk of sudden cardiac death and/or fatal ventricular arrhythmia remains controversial. OBJECTIVE: We analyzed the association between alcohol consumption, genetic traits for alcohol metabolism, and the risk of sudden cardiac death and/or fatal ventricular arrhythmia. METHODS: We identified 397,164 individuals enrolled between 2006 and 2010 from the UK Biobank database and followed them until 2021. Alcohol consumption was categorized as current nondrinkers (nondrinkers and ex-drinkers), mild drinkers, moderate drinkers, or heavy drinkers. Genetic traits of alcohol metabolism were stratified according to the polygenic risk score tertiles. The primary and secondary outcomes were a composite of sudden cardiac death and fatal ventricular arrhythmia as well as their individual components. RESULTS: During follow-up (median 12.5 years), 3543 cases (0.89%) of clinical outcomes occurred. Although mild, moderate, and heavy drinkers showed deceased risks of outcomes compared with current nondrinkers, there was no prognostic difference among nondrinkers, mild drinkers, moderate drinkers, and heavy drinkers. Ex-drinkers showed an increased risk in univariate analysis, but the significance was attenuated after adjusting covariates (hazard ratio 1.19; 95% confidence interval 0.94-1.50). As a continuous variable, alcohol consumption was not associated with clinical outcomes (hazard ratio 1.01; 95% confidence interval 0.99-1.02). Consistent with these findings, there was no association between genetic traits for alcohol metabolism and the risk of clinical outcomes. CONCLUSION: Alcohol consumption was neither a protective factor nor a risk factor for sudden cardiac death or fatal ventricular arrhythmia. Genetic traits of alcohol metabolism were not associated with the clinical prognosis.

Perioperative Management in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Minor Bleeding Risk Procedure: Rationale and Protocol for the PERIXa Study.

Background: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks. Objective: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk. Methods: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events. Conclusion: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk. Trial Registration: Clinicaltrials.gov: NCT05801068.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry.

AIMS: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS AND RESULTS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, P = 0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study.

BACKGROUND: Diabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration. METHODS: Patients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015-2016 were grouped by DM duration: new onset and < 5, 5-9, and ≥ 10 years. Physical activity was classified into four levels: 0, < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (MET)-min/week, with the primary outcome being new-onset AF. RESULTS: The study enrolled 2,392,486 patients (aged 59.3 ± 12.0 years, 39.8% female) with an average follow-up of 3.9 ± 0.8 years and mean DM duration of 5.3 ± 5.1 years. Greater physical activity was associated with a lower AF risk. Lowering of incident AF risk varied with different amounts of physical activity in relation to known DM duration. Among patients with new-onset DM, DM duration < 5 years and 5-9 years and 1,000-1,499 MET-min/week exhibited the lowest AF risk. Physical activity ≥ 1,500 MET-min/week was associated with the lowest incident AF risk in patients with DM duration ≥ 10 years (by 15%), followed DM duration of 5-9 years (12%) and < 5 years (9%) (p-for-interaction = 0.002). CONCLUSIONS: Longer DM duration was associated with a high risk of incident AF, while increased physical activity generally reduced AF risk. Engaging in > 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.

Accelerometer-derived physical activity and the risk of death, heart failure, and stroke in patients with atrial fibrillation: a prospective study from UK Biobank.

OBJECTIVE: Data on cardiovascular outcomes according to objectively measured physical activity (PA) in patients with atrial fibrillation (AF) are scarce. This study explored the associations between PA derived from wrist-worn accelerometers and the risk of death, incident heart failure (HF), and incident stroke in patients with AF. METHODS: From 37 990 patients with AF in UK Biobank, 2324 patients with accelerometer data were included. Weekly moderate-to-vigorous PA (MVPA) duration was computed from accelerometer data. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, incident HF, and incident stroke. Restricted cubic splines estimated the dose-response associations between MVPA duration and the outcomes. The adjusted HRs (aHRs) of the outcomes according to adherence to PA standard guidelines (performing MVPA≥150 min/week) were also evaluated. RESULTS: The mean age was 66.9±6.2 years and 64.9% were male. During a median follow-up of 6.7 years, there were 181 all-cause deaths, 62 cardiovascular deaths, 225 cases of incident HF, and 91 cases of incident stroke; the overall incidence rate per 1000 patient-years was 11.76, 4.03, 15.16 and 5.99, respectively. There was a linear inverse dose-response relationship between MVPA (≥108 min/week) and all-cause mortality. Performing MVPA for 105-590 min/week was associated with a lower risk of HF than those with no measurable MVPA. The risk of stroke and cardiovascular mortality was not associated with MVPA. Performing guideline-adherent MVPA was related to a 30% lower risk of all-cause mortality (aHR: 0.70 (0.50-0.98), p=0.04) and 33% lower risk of HF (aHR 0.67 (0.49-0.93), p=0.02). CONCLUSION: In patients with AF, accelerometer-derived PA data supports lower risks of all-cause mortality and HF according to a greater level of MVPA and adherence to PA guidelines. Regular MVPA should be encouraged in patients with AF as a part of integrated management.

Neuroticism and the Risk of Atrial Fibrillation: An Observational Epidemiologic and Mendelian Randomization Study.

Background: The association between neuroticism and atrial fibrillation (AF) remains unknown. Objectives: This study aimed to assess the epidemiological and causal relationships between neuroticism and AF. Methods: Individuals without AF history were selected From the UK Biobank nationwide prospective cohort study. Participants were divided into 2 groups (high and low) based on the median summary score from a self-questionnaire of 12 neurotic behavior domains. The 10-year AF risk was compared between the neuroticism score groups using inverse probability of treatment weighting. The causal relationship between neuroticism and AF was evaluated using a 2-sample summary-level Mendelian randomization with the inverse variance-weighted method. Results: Of 394,834 participants (mean age 56.3 ± 8.1 years, 45.9% male), AF occurred in 23,509 (6.0%) during a 10-year follow-up. The risk of incident AF significantly increased in the high neuroticism score group (score ≥4) (inverse probability of treatment weighting-adjusted HR: 1.05; 95% CI: 1.02-1.09; P = 0.005) compared with the low neuroticism group. In the subgroup analysis, younger age, lower body mass index, or nonsmoker/ex-smoker participants were particularly susceptible to increased AF risk due to high neuroticism scores. A Mendelian randomization analysis showed a significant causal relationship between an increase in neuroticism score and increased risk of AF (OR by inverse variance-weighted method 1.06; 95% CI: 1.02-1.11; P = 0.007) without evidence of reverse causality. Conclusions: There was a significant longitudinal and causal relationship between neuroticism and AF. An integrated care including active mental health screening and management may benefit in high-risk populations.

Association between antithrombotic therapy after stroke in patients with atrial fibrillation and the risk of net clinical outcome: an observational cohort study.

AIMS: Data on the optimal use of antithrombotic drugs and associated clinical outcomes in patients with atrial fibrillation (AF) and acute ischaemic stroke (IS) are limited. We investigated the prescription patterns of antithrombotics in community practice and long-term clinical prognosis according to early post-stroke antithrombotic therapy in patients with AF and acute IS. METHODS AND RESULTS: Patients with AF who were admitted for acute IS at a single tertiary hospital in 2010-2020 were retrospectively reviewed. Clinical profiles including the aetiology of stroke and prescription patterns of antithrombotics were identified. The net clinical outcome (NCO)-the composite of recurrent stroke, any bleeding, hospitalization or emergency department visits for cardiovascular (CV) events, and death-was compared according to the antithrombotic therapy at the first outpatient clinic visit [oral anticoagulation (OAC) alone vs. antiplatelet (APT) alone vs. OAC/APT(s)] following discharge. A total of 918 patients with AF and acute IS (mean age, 72.6 years; male, 59.3%; mean CHA2DS2-VASc score 3.3) were analysed. One-third (33.9%, n = 310) of patients were simultaneously diagnosed with AF and IS. The most common aetiology of IS was cardioembolism (71.2%), followed by undetermined aetiology (19.8%) and large artery atherosclerosis (6.0%). OAC, APT(s), and concomitant OAC and APT(s) were prescribed in 33.4%, 11.1%, and 53.4% of patients during admission that changed to 67.0%, 9.1%, and 21.7% at the first outpatient clinic, and were mostly continued up to one year after IS. Non-prescription of OAC was observed in 11.3% of post-stroke patients with AF. During a median follow-up of 2.1 years, the overall incidence rate of NCO per 100 patient-year (PY) was 20.14. APT(s) monotherapy presented the highest cumulative risk of NCO (adjusted hazard ratio 1.47, 95% confidence interval 1.08-2.00, P = 0.015; with reference to OAC monotherapy) mainly driven by the highest rates of recurrent stroke and any bleeding. OAC/APT(s) combination therapy was associated with a 1.62-fold significantly higher risk of recurrent stroke (P = 0.040) and marginally higher risk of any bleeding than OAC monotherapy. CONCLUSION: Approximately one-third of acute IS in AF have a distinctive mechanism from cardioembolism. Although APT was frequently prescribed in post-stroke patients with AF, no additive clinical benefit was observed. Adherence to OAC treatment is essential to prevent further CV adverse events in patients with AF and IS.

Risk of newly developed atrial fibrillation by alcohol consumption differs according to genetic predisposition to alcohol metabolism: a large-scale cohort study with UK Biobank.

BACKGROUND: The predictive relationship between mild-to-moderate alcohol consumption and the risk of incident atrial fibrillation (AF) remains controversial. OBJECTIVE: We investigated whether the relationship between alcohol consumption and the risk of incident AF could be associated with the genetic predisposition to alcohol metabolism. METHODS: A total of 399,329 subjects with genetic data from the UK Biobank database, enrolled between 2006 and 2010, were identified and followed for incident AF until 2021. Genetic predisposition to alcohol metabolism was stratified according to the polygenic risk score (PRS) tertiles. Alcohol consumption was categorized as non-drinkers, mild-to-moderate drinkers (< 30 g/day), and heavy drinkers (≥ 30 g/day). RESULTS: During the follow-up (median 12.2 years), 19,237 cases of AF occurred. When stratified by PRS tertiles, there was a significant relationship between genetic predisposition to alcohol metabolism and actual alcohol consumption habits (P < 0.001). Mild-to-moderate drinkers showed a decreased risk of AF (HR 0.96, 95% CI 0.92-0.99), and heavy drinkers showed an increased risk of AF (HR 1.06, 95% CI 1.02-1.10) compared to non-drinkers. When stratified according to PRS tertiles for genetic predisposition to alcohol metabolism, mild-to-moderate drinkers had equivalent AF risks, and heavy drinkers showed increased AF risk in the low PRS tertile group. However, mild-to-moderate drinkers had decreased AF risks and heavy drinkers showed similar risks of AF in the middle/high PRS tertile groups. CONCLUSIONS: Differential associations between alcohol consumption habits and incident AF across genetic predisposition to alcohol metabolism were observed; individuals with genetic predisposition to low alcohol metabolism were more susceptible to AF.

Sex difference in the age-related decline of global longitudinal strain of left ventricle.

Global longitudinal strain (GLS) is a valuable indicator of subclinical myocardial dysfunction. Whether the effect of aging on subclinical left ventricular dysfunction is sex-specific is not well documented. This study aimed to identify age-related changes in GLS according to sex in patients with a normal left ventricular ejection fraction (LVEF). In this cross-sectional, single-center cohort study in Korea, participants who underwent GLS measurement using 2D speckle-tracking echocardiography were retrospectively reviewed, and participants with normal LVEF (≥ 55%) without documented cardiovascular disease were included. Reduced GLS was defined as absolute values below 18%. Of 682 study participants (mean age, 58; female, 51.5%), 209 (30.6%) had reduced GLS. Females with reduced GLS were older than those with normal GLS (68 vs. 58 years, P < 0.001); with no difference of age in males (55 vs. 57 years; P = 0.265). Univariate analysis showed age to correlate significantly with reduced GLS only in female (r = - 0.364; P < 0.001). In multivariable analysis, female > 66 years old had significantly higher risk of reduced GLS (Odds ratio 2.66; 95% CI 1.22-5.76; P = 0.014). In participants with normal LVEF, GLS decreased with age in females but not in males. Particularly, females aged 66 years and older had a significantly higher risk of reduced GLS. These findings suggest that GLS could be a valuable parameter for assessing subclinical cardiac dysfunction, especially in older females.

Neuroticism and sudden cardiac death: a prospective cohort study from UK biobank.

OBJECTIVE: There is a paucity of evidence on the risk of sudden cardiac death (SCD) according to the degree of neuroticism. We sought to evaluate the association between neuroticism and the long-term risk of SCD. METHODS: From the UK Biobank nationwide prospective cohort, participants free from previous SCD, ventricular arrhythmias, implantable cardioverter-defibrillator (ICD) insertion, depression, schizophrenia, and bipolar disorder were selected. The 12-item scale of neuroticism measurement (neuroticism score) was categorized into high (≥ 3) and low (< 3) groups. The primary outcome was SCD including ventricular fibrillation (VF) at median 12.6 years of follow-up. The outcomes were compared between the groups using multivariable Cox regression and inverse probability of treatment weighting (IPTW). RESULTS: A total of 377,563 participants (aged 56.5 ± 8.1, 53.1% women) were analyzed. The high neuroticism score group had a significantly lower risk of SCD (adjusted hazard ratio [aHR] = 0.87, 95% confidence interval [CI] 0.79-0.96, P = 0.007; IPTW-adjusted HR [IPTW-HR] 0.87 [0.77-0.97], P = 0.016) than the low neuroticism score group. The effect of a high neuroticism score on the decreased risk of SCD was more prominent in women (IPTW-HR 0.71 [0.56-0.89], P = 0.003) than in men (IPTW-HR 0.93 [0.82-1.07], P = 0.305, P-for-interaction = 0.043). Sex differences were observed among independent predictors for incident SCD, emphasizing the protective role of a high neuroticism score and moderate-to-vigorous physical activity only in women. CONCLUSIONS: A high neuroticism score was significantly associated with a lower risk of SCD, particularly in women. Efforts to unveil the causal and mechanistic relationship between personality phenotypes and the risk of SCD should be continued.

Personal Health Data Tracking by Blind and Low-Vision People: Survey Study.

BACKGROUND: Personal health technologies, including wearable tracking devices and mobile apps, have great potential to equip the general population with the ability to monitor and manage their health. However, being designed for sighted people, much of their functionality is largely inaccessible to the blind and low-vision (BLV) population, threatening the equitable access to personal health data (PHD) and health care services. OBJECTIVE: This study aims to understand why and how BLV people collect and use their PHD and the obstacles they face in doing so. Such knowledge can inform accessibility researchers and technology companies of the unique self-tracking needs and accessibility challenges that BLV people experience. METHODS: We conducted a web-based and phone survey with 156 BLV people. We reported on quantitative and qualitative findings regarding their PHD tracking practices, needs, accessibility barriers, and work-arounds. RESULTS: BLV respondents had strong desires and needs to track PHD, and many of them were already tracking their data despite many hurdles. Popular tracking items (ie, exercise, weight, sleep, and food) and the reasons for tracking were similar to those of sighted people. BLV people, however, face many accessibility challenges throughout all phases of self-tracking, from identifying tracking tools to reviewing data. The main barriers our respondents experienced included suboptimal tracking experiences and insufficient benefits against the extended burden for BLV people. CONCLUSIONS: We reported the findings that contribute to an in-depth understanding of BLV people's motivations for PHD tracking, tracking practices, challenges, and work-arounds. Our findings suggest that various accessibility challenges hinder BLV individuals from effectively gaining the benefits of self-tracking technologies. On the basis of the findings, we discussed design opportunities and research areas to focus on making PHD tracking technologies accessible for all, including BLV people.

Electrochemical detection and analysis of tumor-derived extracellular vesicles to evaluate malignancy of pancreatic cystic neoplasm using integrated microfluidic device.

Tumor-derived extracellular vesicles (tdEVs) are one of the most promising biomarkers for liquid biopsy-based cancer diagnostics, owing to the expression of specific membrane proteins of their cellular origin. The investigation of epithelial-to-mesenchymal transition (EMT) in cancer using tdEVs is an alternative way of evaluating the risk of malignancy transformation. An ultra-sensitive selection and detection methodology is an essential step in developing a tdEVs-based cancer diagnostic device. In this study, we developed an indium-tin-oxide (ITO) sensor integrated microfluidic device consisting of two main parts: 1) a multi-orifice flow-fractionation (MOFF) channel for extraction of pure EVs by removing blood cellular debris, and 2) an ITO sensor coupled with a geometrically activated surface interaction (GASI) channel for enrichment and quantification of tdEV. The microfluidic channel and the ITO sensors are assembled with a 3D printed magnetic housing to prevent sample leakage and to easily attach/detach the sensors to/from the microfluidic channel. The tdEVs were successfully captured on the specific antibody modified ITO surfaces in the integrated microfluidic channel. The integrated sensors showed an excellent linear response between 103 and 109 tdEVs/mL. Simultaneous evaluation of the epithelial and mesenchymal markers on the tdEV surfaces successfully revealed the EMT index of the corresponding pancreatic cancer cells. Our ITO sensor integrated microfluidic device showed excellent detection in the clinically relevant tdEVs-concentration range for patients with pancreatic cystic neoplasms. Hence, this system is expected to open a new avenue for liquid biopsy-based cancer prognostics and diagnostics.

Simple ultrasensitive electrochemical detection of the DBP plasticizer for the risk assessment of South Korean river waters.

Rapid detection of contaminants for the purpose of sensitive and quantitative monitoring of environmental hazards is an essential first step in realizing the avoidance of human health risks. In this regard, we present a fast and simple electrochemical method of detecting di-n-butyl phthalate (DBP) from river water samples using a phthalic acid group specific aptamer modified on a gold nanoparticle (AuNP) functionalized graphene oxide nano-platelet (GO) and ionic liquid (IL) nanocomposite. Here, the IL/GO nanocomposite allows an enhanced interaction with phthalate esters, thereby increasing the sensitivity of the sensor surface. The proposed sensor showed a wide linear dynamic range from 0.14 pg mL-1 to 0.35 ng mL-1 and from 0.35 ng mL-1 to 7 ng mL-1 with a detection limit of ≤0.042 pg mL-1, which were evaluated using standard, analytical grade DBP; the limit of quantification was determined using different concentrations of DBP in DI water in comparison with gas chromatography-mass spectroscopy (GC/MS) values. The proposed sensor was used to monitor the DBP concentrations in river water samples collected from various locations across South Korea. The quantitative data from the measurements in comparison with standard GC/MS values were then used to ascertain the human health risk posed by the daily consumption of these river waters.

Electrochemical biosensor for nucleic acid amplification-free and sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA via CRISPR/Cas13a trans-cleavage reaction.

The outbreak of the COVID-19 pandemic has led to millions of fatalities worldwide. For preventing epidemic transmission, rapid and accurate virus detection methods to early identify infected people are urgently needed in the current situation. Therefore, an electrochemical biosensor based on the trans-cleavage activity of CRISPR/Cas13a was developed in this study for rapid, sensitive, and nucleic-acid-amplification-free detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, a redox probe conjugated with ssRNA is immobilized on the electrode surface modified with a nanocomposite (NC) and gold nanoflower (AuNF) for enhancing the sensing performance. The SARS-CoV-2 RNA is captured by the Cas13a-crRNA complex, which triggers the RNase function of Cas13a. The enzymatically activated Cas13a-crRNA complex is subsequently introduced to the reRNA-conjugated electrochemical sensor, and consequently cleaves the reRNA. A change in current occurs due to the release of the redox molecule labeled on the reRNA, which is trans-cleaved from the Cas13a-crRNA complex. The biosensor can detect as low as 4.4 × 10-2 fg/mL and 8.1 × 10-2 fg/mL of ORF and S genes, respectively, over a wide dynamic range (1.0 × 10-1 to 1.0 × 105 fg/mL). Moreover, the biosensor was evaluated by measuring SARS-CoV-2 RNA spiked in artificial saliva. The recovery of the developed sensor was found to be in an agreeable range of 96.54-101.21%. The designed biosensor lays the groundwork for pre-amplification-free detection of ultra-low concentrations of SARS-CoV-2 RNA and on-site and rapid diagnostic testing for COVID-19.

Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0.

This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.

All-in-one platform for salivary cotinine detection integrated with a microfluidic channel and an electrochemical biosensor.

Medical disorders caused by second-hand smoke are a major public health concern worldwide. To estimate the level of second-hand smoke exposure, salivary diagnostics for cotinine analysis is a compelling alternative in conventional diagnostics using bio-fluids, such as blood and urine, owing to its simple and non-invasive collection method. However, there are several critical issues, such as tedious multisteps, demand for expertise, and field unavailability to collect and transport the purified saliva for further analysis. Here, an all-in-one platform is presented to simply collect real human saliva and directly deliver it onto the biosensing surface. The platform consists of a commercial cotton-swab-type collector, 3D-printed housing, and microfluidic channel integrated with an electrochemical competitive immunosensor to evaluate the level of salivary cotinine. The immunosensor is based on a competitive binding assay between cotinine-conjugated horseradish peroxidase (C-HRP) and cotinine for anti-cotinine binding sites. The current responses obtained from the HRP-thionine-H2O2 system decreased proportionally to the cotinine concentration. This immunosensor successfully detected its target over a range of 1 × 10-1 to 1 × 104 pg ml-1 with a low limit of detection of 6 × 10-2 pg ml-1 and a limit of quantification of 1 × 10-1 pg ml-1. In addition, the platform is applicable to various commercial cotton-swab-type saliva collectors and can successfully transfer the saliva in wide flow rates ranging from 0.1 to 30 ml min-1 without leakage or damage to the sensing surface. Furthermore, the practicality of the proposed platform was evaluated by measuring cotinine in real human saliva from eight non-smokers. The concentration of cotinine was from 45.7 to 890.8 pg ml-1, which was in good agreement with that measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The introduced all-in-one platform represented a reliable performance delivering simple and practical steps in salivary diagnostics.

Mobile diagnostics: next-generation technologies for in vitro diagnostics.

The emergence of a wide range of applications of smartphones along with advances in 'liquid biopsy' has significantly propelled medical research particularly in the field of in vitro diagnostics (IVD). Herein, we have presented a detailed analysis of IVD, its associated critical concerns and probable solutions. It also demonstrates the transition in terms of analytes from minimally invasive (blood) to non-invasive (urine, saliva and sweat) and depicts how the different features of a smartphone can be integrated for specific diagnostic purposes. This review basically highlights recent advances in the applications of smartphone-based biosensors in IVD taking into account the following factors: accuracy and portability; quantitative and qualitative analysis; and centralization and decentralization tests. Furthermore, the critical concerns and future direction of diagnostics based on smartphones are also discussed.

Relationship between prenatal and postnatal exposures to folate and risks of allergic and respiratory diseases in early childhood.

BACKGROUND: It is uncertain whether folate is risk or preventive factor for allergic and respiratory diseases. OBJECTIVE: To determine the relationship between maternal or offspring folate status and subsequent development of allergic and respiratory diseases in early childhood. METHODS: In total, 917 mother-child pairs from a prospective birth cohort in South Korea were studied. Data regarding the children's allergic and respiratory outcomes were obtained from standardized questionnaires completed by the mothers at postnatal months 6, 12, and 24. Serum folate levels were measured in the mothers at mid- and late-pregnancy, and in their children at 24 months of age. Atopic biomarkers were measured in the cord blood (CB) and at 24 months after birth. Biomarkers and clinical outcomes were analyzed and compared between the mother-child pairs divided into two groups according to median serum folate status at mid- and late-pregnancy. RESULTS: Serum folate levels during mid-pregnancy were inversely associated with CB eosinophil count (adjusted odds ratio [OR] 0.72, 95% confidence interval [CI], 0.54-0.96) and positively associated with CB interleukin-10 levels (1.47, 1.11-1.94). Maternal folate level above the median value (≥9.5 ng/ml) during mid-pregnancy was associated with a decreased risk for the child of lower respiratory tract infections (LRTIs) at 6 months of age (adjusted OR 0.50, 95% CI 0.28-0.91) and atopic dermatitis (AD) at 24 months (adjusted OR 0.52, 95% CI 0.31-0.88), but not with LRTIs and AD at other ages. CONCLUSIONS: A relatively high maternal serum folate level in mid-pregnancy was associated with a decreased risk of LRTIs and AD in early childhood.

Rash in psychiatric and nonpsychiatric adolescent patients receiving lamotrigine in Korea: a retrospective cohort study.

OBJECTIVE: Lamotrigine is a widely used medication for psychiatric disorders and epilepsy, but the adverse effects of this drug in adolescent Korean patients have not yet been investigated. In the present study, we sought to compare the incidence and impact of lamotrigine-induced skin rashes and different pattern of adverse events in psychiatric and nonpsychiatric adolescent patients. METHODS: Using a retrospective cohort design, all of the charts were reviewed for adolescents (13 to 20 years old), treated with lamotrigine during the previous 2 years in the Child and Adolescent Psychiatric Clinic and Pediatric Neurologic Clinic of the Ulsan University Hospital in South Korea. RESULTS: Of the 102 subjects, 23 patients developed a skin rash. All of these rashes were observed within 7 weeks of the initiation of the lamotrigine therapy. Only one subject developed a serious rash, which was diagnosed as Stevens-Johnson syndrome. Although the psychiatric subjects were administered statistically lower doses of lamotrigine during weeks 1 through 5 and at week 12, the likelihood of developing a rash was not significantly different between the psychiatric and nonpsychiatric patients. CONCLUSION: Careful dose escalation and close observation of side effects for the first 7 weeks of treatment is important. The present study reveals the tolerability of lamotrigine in an adolescent population, although a double-blind, controlled trial is needed to confirm these findings.