Angiotensin Receptor Blockers and the Risk of Suspected Drug-Induced Liver Injury: A Retrospective Cohort Study Using Electronic Health Record-Based Common Data Model in South Korea.

INTRODUCTION: Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI. OBJECTIVE: We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017-31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan. METHODS: Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R. RESULTS: In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55-0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28-8.12]). CONCLUSIONS: We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice.

Antibiofilm and antithrombotic hydrogel coating based on superhydrophilic zwitterionic carboxymethyl chitosan for blood-contacting devices.

Blood-contacting devices must be designed to minimize the risk of bloodstream-associated infections, thrombosis, and intimal lesions caused by surface friction. However, achieving effective prevention of both bloodstream-associated infections and thrombosis poses a challenge due to the conflicting nature of antibacterial and antithrombotic activities, specifically regarding electrostatic interactions. This study introduced a novel biocompatible hydrogel of sodium alginate and zwitterionic carboxymethyl chitosan (ZW@CMC) with antibacterial and antithrombotic activities for use in catheters. The ZW@CMC hydrogel demonstrates a superhydrophilic surface and good hygroscopic properties, which facilitate the formation of a stable hydration layer with low friction. The zwitterionic-functionalized CMC incorporates an additional negative sulfone group and increased negative charge density in the carboxyl group. This augmentation enhances electrostatic repulsion and facilitates the formation of hydration layer. This leads to exceptional prevention of blood clotting factor adhesion and inhibition of biofilm formation. Subsequently, the ZW@CMC hydrogel exhibited biocompatibility with tests of in vitro cytotoxicity, hemolysis, and catheter friction. Furthermore, in vivo tests of antithrombotic and systemic inflammation models with catheterization indicated that ZW@CMC has significant advantages for practical applications in cardiovascular-related and sepsis treatment. This study opens a new avenue for the development of chitosan-based multifunctional hydrogel for applications in blood-contacting devices.

Prevalence and Clinical Characteristics of Mitochondrial DNA Mutations in Korean Patients With Sensorineural Hearing Loss.

BACKGROUND: Mutations in mitochondrial DNA (mtDNA) are associated with several genetic disorders, including sensorineural hearing loss. However, the prevalence of mtDNA mutations in a large cohort of Korean patients with hearing loss has not yet been investigated. Thus, this study aimed to investigate the frequency of mtDNA mutations in a cohort of with pre- or post-lingual hearing loss of varying severity. METHODS: A total of 711 Korean families involving 1,099 individuals were evaluated. Six mitochondrial variants associated with deafness (MTRNR1 m.1555A>G, MTTL1 m.3243A>G, MTCO1 m.7444G>A and m.7445A>G, and MTTS1 m.7471dupC and m.7511T>C) were screened using restriction fragment length polymorphism. The prevalence of the six variants was also analyzed in a large control dataset using whole-genome sequencing data from 4,534 Korean individuals with unknown hearing phenotype. RESULTS: Overall, 12 of the 711 (1.7%) patients with hearing loss had mtDNA variants, with 10 patients from independent families positive for the MTRNR1 m.1555A>G mutation and 2 patients positive for the MTCO1 m.7444G>A mutation. The clinical characteristics of patients with the mtDNA variants were characterized by post-lingual progressive hearing loss due to the m.1555A>G variant (9 of 472; 1.9%). In addition, 18/4,534 (0.4%) of the Korean population have mitochondrial variants associated with hearing loss, predominantly the m.1555A>G variant. CONCLUSION: A significant proportion of Korean patients with hearing loss is affected by the mtDNA variants, with the m.1555A>G variant being the most prevalent. These results clarify the genetic basis of hearing loss in the Korean population and emphasize the need for genetic testing for mtDNA variants.

Aneurysm and Artery Dissection After Oral VEGFR-TKI Use in Adults With Cancer.

Importance: The association of tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR-TKIs) with aneurysm and artery dissection (AAD) has been frequently reported in spontaneous reporting databases. Objective: To investigate the risk and incidence of AAD occurrence in patients with cancer treated with oral VEGFR-TKIs, with capecitabine as an active comparator. Design, Setting, and Participants: This national, historical cohort study was conducted using national claims data from the National Health Insurance Service in Korea from 2007 to 2020, with a 1-year follow-up. Patients with cancer aged 40 years or older prescribed oral VEGFR-TKIs or capecitabine were enrolled. Data were analyzed from September 2022 through April 2023. Exposure: Oral VEGFR-TKIs (sorafenib, regorafenib, vandetanib, sunitinib, lenvatinib, axitinib, and pazopanib) or capecitabine as a comparator. Main Outcomes and Measures: Hazard ratios (HRs) were used to investigate the association between VEGFR-TKI use and AAD after propensity score matching. The primary outcome was AAD, and secondary outcomes were aortic aneurysm and dissection and AAD with rupture. Outcomes were defined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes. Results: Among 127 710 patients with cancer eligible for the study (80 386 males [62.9%]; mean [SD] age, 62.6 [10.9] years), 37 308 patients received VEGFR-TKIs and 90 402 patients received capecitabine. Among 27 535 matched patients receiving VEGFR-TKIs, the incidence of AAD within 1 year of treatment initiation was 6.0 per 1000 person-years. The median (IQR) time to AAD onset in the matched AAD group was 114 (67-257) days after treatment initiation, with the highest incidence observed during the first 3 months (45 incidents vs 31, 17, and 16 incidents during 3- to 6-month, 6- to 9-month, and 9- to 12-month periods, respectively). Cox regression modeling showed that the risk of AAD occurrence was significantly higher among patients prescribed VEGFR-TKIs than those receiving capecitabine (HR, 1.48; 95% CI, 1.08-2.02); similar results were obtained among females (HR, 2.08; 95% CI, 1.26-3.42), older adults (aged ≥65 years; HR, 1.42; 95% CI, 1.01-1.99), and patients with dyslipidemia (HR, 1.58; 95% CI, 1.11-2.24). Conclusions and Relevance: In this study, the use of oral VEGFR-TKIs was associated with an increased risk of AAD occurrence. These findings elucidate vascular toxic effects and may provide a substantial reference for reducing the socioeconomic burden of adverse events associated with VEGFR-TKI use.

Manipulation and Direct Characterization of Polymer/Small-Molecule Interface Morphology in Bulk-Heterojunction Solar Cell.

To investigate the effect of miscibility between conjugated polymers (CPs) and Y6 on bulk-heterojunction (BHJ) type morphology, we propose three different CPs with similar chemical structures but different miscibility with Y6. After selectively removing Y6 from the CP/Y6 blend films, their interface morphology and interlocked dimensions are quantitatively compared using a square-wave model. As CP-Y6 miscibility increases, a higher intermixed interface is formed, providing an enlarged CP-Y6 interface area. Conversely, as the miscibility between CP and Y6 decreases, the height and width of the interlocked dimensions formed by phase separation gradually decrease and increase, respectively. Additionally, when the CP-Y6 interface morphology and electrical properties of the corresponding organic photovoltaic (OPV) device are correlated, as the highly intermixed CP-Y6 interface develops, the exciton dissociation efficiency increases owing to the reduced exciton diffusion length to be dissociated, but the bimolecular recombination tends to deteriorate simultaneously. Furthermore, if the miscibility between CP and Y6 is excessive, the formation of a charge transport pathway through phase separation is interrupted, deteriorating the charge transport capability in BHJ-type OPVs. However, it was confirmed that introducing F atoms into the conjugated backbone of CP can reduce the bimolecular recombination, providing ameliorated light-harvesting efficiency.

Side-Chain-Assisted Transition of Conjugated Polymers from a Semiconductor to Conductor and Comparison of Their NO2 Sensing Characteristics.

To investigate the effect of a side chain on the electrical properties of a conjugated polymer (CP), we designed two different CPs containing alkyl and ethylene glycol (EG) derivatives as side chains on the same conjugated backbone with an electron donor-acceptor (D-A) type chain configuration. PTQ-T with an alkyl side chain showed typical p-type semiconducting properties, whereas PTQ-TEG with an EG-based side chain exhibited electrically conductive behavior. Both CPs generated radical species owing to their strong D-A type conjugated structure; however, the spin density was much greater in PTQ-TEG. X-ray photoelectron spectroscopy analysis revealed that the O atoms of the EG-based side chains in PTQ-TEG were intercalated with the conjugated backbone and increased the carrier density. Upon application to a field-effect transistor sensor for PTQ-T and resistive sensor for PTQ-TEG, PTQ-TEG exhibited a better NO2 detection capability with faster signal recovery characteristics than PTQ-T. Compared with the relatively rigid alkyl side chains of PTQ-T, the flexible EG-based side chains in PTQ-TEG have a higher potential to enlarge the free volume as well as improve NO2-affinity, which promotes the diffusion of NO2 in and out of the PTQ-TEG film, and ultimately resulting in better NO2 detection capabilities.

`Risk of cardiovascular disease associated with febuxostat versus allopurinol use in patients with gout: a retrospective cohort study in Korea.

Febuxostat is the drug used to treat hyperuricemia in patients with gout. Recently, the usage of Febuxostat has been controversial over the side effects in cardiovascular. The study aimed to comparatively analyze the risk of cardiovascular disease associated with febuxostat and allopurinol use in Korean patients with gout. A cohort study was conducted using national insurance claim data from the Health Insurance Review and Assessment Service (HIRA). Adult patients who were diagnosed with gout and prescribed febuxostat or allopurinol more than once from July 1, 2015, to June 30, 2018 were studied. The outcome was cardiovascular disease. Analysis was performed using Cox's proportional hazard model following 1:1 propensity score matching to estimate the hazard ratio with a 95% confidence interval. In total, 90,590 patients were defined as the final study cohort who had an average follow-up of 467 days, including 28,732 and 61,858 patients in the febuxostat and allopurinol groups, respectively. After the 1:1 propensity score matching, the risk of cardiovascular disease in the febuxostat group was significantly higher than in the allopurinol group (HR: 1.17; 95% CI: 1.10-1.24). In the sensitivity analysis, the risk of cardiovascular disease in the febuxostat group was significantly higher than in the allopurinol group (HR: 1.09; 95% CI: 1.04-1.15). However, further sensitivity analysis showed no statistically significant difference between the febuxostat group and allopurinol group after adjusting for cardiovascular disease history before the index date. Similarly, no statistically significant difference was found between the two drugs in the subgroup analysis. Febuxostat was not associated with a significantly increased risk of cardiovascular disease.

Depression risk associated with the use of 5α-reductase inhibitors versus α-blockers: A retrospective cohort study in South Korea.

BACKGROUND: One of the most prescribed treatments for benign prostatic hyperplasia (BPH) is 5α-reductase inhibitors (5ARI). Europe experienced recent safety issues involving 5ARI and depression symptoms, with similar findings being seen in Western countries. The South Korea has updated the drug label in accordance with European recommendations, but the relevant evidence was insufficient. This study compared the use of 5ARI versus α-blocker (AB) as a treatment for BPH and related risks of depression to provide evidence based on the Korean population. METHODS: This was a retrospective cohort study using South Korea's Health Insurance Review & Assessment Service claim data from 2011 to 2017. New patients diagnosed in men with BPH and taking medications that contained either 5ARI or AB between July 1, 2013, and June 30, 2015, were included (n = 1,461 5ARI; n = 18,650 AB). The primary outcome was depression defined per the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10: F32-34, F38, F412, F432). Logistic regression was used to implement 1:1 propensity score (PS) matching of patients taking 5ARI to those taking AB to adjust for confounding. Cox proportional hazard models were used to compare the risk of depression associated with 5ARI versus AB. RESULTS: Balance in baseline characteristics between the treatment groups were achieved within PS matched pairs (1,461 pairs). Compared to the AB medication group, the 5ARI group had lower depression (HR: 0.69, 95% CI: [0.51-0.92]). However, we could not find a clinically relevant, statistical difference after PS matching (HR: 0.91, 95% CI: [0.61-1.36]). CONCLUSIONS: The risk of depression associated with 5ARI was not meaningfully different from AB in Korea, which suggests that medical officials should provide the most appropriate medication for BPH patients by considering both treatment benefits and depression risk.

Multifunction-Harnessed Afterglow Nanosensor for Molecular Imaging of Acute Kidney Injury In Vivo.

Afterglow is superior to other optical modalities for biomedical applications in that it can exclude the autofluorescence background. Nevertheless, afterglow has rarely been applied to the high-contrast "off-to-on" activatable sensing scheme because the complicated afterglow systems hamper the additional inclusion of sensory functions while preserving the afterglow luminescence. Herein, a simple formulation of a multifunctional components-incorporated afterglow nanosensor (MANS) is developed for the superoxide-responsive activatable afterglow imaging of cisplatin-induced kidney injury. A multifunctional iridium complex (Ir-OTf) is designed to recover its photoactivities (phosphorescence and the ability of singlet oxygen-generating afterglow initiator) upon exposure to superoxide. To construct the nanoscopic afterglow detection system (MANS), Ir-OTf is incorporated with another multifunctional molecule (rubrene) in the polymeric micellar nanoparticle, where rubrene also plays dual roles as an afterglow substrate and a luminophore. The multiple functions covered by Ir-OTf and rubrene renders the composition of MANS quite simple, which exhibits superoxide-responsive "off-to-on" activatable afterglow luminescence for periods longer than 11 min after the termination of pre-excitation. Finally, MANS is successfully applied to the molecular imaging of cisplatin-induced kidney injury with activatable afterglow signals responsive to pathologically overproduced superoxide in a mouse model without autofluorescence background.

Risk of aortic aneurysm and aortic dissection with the use of fluoroquinolones in Korea: a nested case-control study.

BACKGROUND: Recent studies have raised concern about the association of fluoroquinolones with an increased risk of aortic aneurysm and aortic dissection. We aimed to evaluate such risk in a Korean population. METHODS: We conducted a nested case-control study using data from the National Health Insurance Service collected from 2013 to 2017 in Korea. The study cohort included patients older than 40 years and excluded patients who had used fluoroquinolones or been diagnosed with aortic aneurysm, aortic dissection, or related diseases 1 year prior to the cohort entry date. We randomly matched four controls in the risk set with each case of aortic aneurysm and aortic dissection (same sex, age, and cohort entry date). We assessed the risk of aortic aneurysm and aortic dissection from fluoroquinolones and adjusted for potential confounders using a conditional logistic regression model. RESULTS: A total of 29,638 aortic aneurysm and aortic dissection patients were identified between 2014 and 2017. The use of fluoroquinolones within a year was associated with a 10% increased risk of aortic aneurysm and aortic dissection (adjusted odds ratio: 1.10, 95% CI 1.07-1.14, p < 0.05) compared with nonusers. The risk was higher in patients who had used fluoroquinolones within 60 days (adjusted odds ratio: 1.53, 95% CI 1.46-1.62, p < 0.05). The risk of aortic aneurysm and aortic dissection positively correlated with the cumulative dose and duration of fluoroquinolone therapy (p < 0.001). CONCLUSIONS: Our study provides real-world evidence of the risk of aortic aneurysm and aortic dissection from fluoroquinolones in Korea. Patients and medical professionals should be aware that fluoroquinolones can increase the risk of aortic aneurysm and aortic dissection, which may be acerbated by high dosage and duration of use.

Risk of genital and urinary tract infections associated with SGLT-2 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes mellitus: A retrospective cohort study in Korea.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are antidiabetic drugs with associated safety concerns regarding the risk of genital and urinary tract infections. This study assessed the risk of genital and urinary tract infections associated with prescription of SGLT-2 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM) compared to dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylurea (SU), and thiazolidinedione (TZD). We conducted a retrospective cohort study using the NHIS-National Health Insurance-Database in Korea from 2014 to 2017. Patients aged ≥19 years and those diagnosed with T2DM prior to drug prescription were enrolled. The outcomes were genital and urinary tract infections. Analysis was performed using Cox's proportional hazard model following 1:1 propensity score matching to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Among the 107 131 patients included in the study, a total of 7738, 7145, and 2175 patients were assigned to the DPP-4 inhibitors, SU, and TZD comparator groups, using the propensity score (PS) of each comparator based on 7741 people in the assessed drug SGLT-2 inhibitor group. SGLT-2 inhibitors were associated with a higher risk of genital infections than DPP-4 inhibitors (HR: 2.39, 95% CI: 2.07-2.76), SU (HR: 3.23, 95% CI: 2.73-3.81), and TZD (HR: 3.23, 95% CI: 2.35-4.44), as an add-on therapy to metformin. Similar results were observed for the risk of urinary tract infections. In conclusion, SGLT-2 inhibitors are significantly associated with a higher risk of genital and urinary tract infections compared to DPP-4 inhibitors, SU, and TZD.

Powerful use of automated prioritization of candidate variants in genetic hearing loss with extreme etiologic heterogeneity.

Variant prioritization of exome sequencing (ES) data for molecular diagnosis of sensorineural hearing loss (SNHL) with extreme etiologic heterogeneity poses a significant challenge. This study used an automated variant prioritization system ("EVIDENCE") to analyze SNHL patient data and assess its diagnostic accuracy. We performed ES of 263 probands manifesting mild to moderate or higher degrees of SNHL. Candidate variants were classified according to the 2015 American College of Medical Genetics guidelines, and we compared the accuracy, call rates, and efficiency of variant prioritizations performed manually by humans or using EVIDENCE. In our in silico panel, 21 synthetic cases were successfully analyzed by EVIDENCE. In our cohort, the ES diagnostic yield for SNHL by manual analysis was 50.19% (132/263) and 50.95% (134/263) by EVIDENCE. EVIDENCE processed ES data 24-fold faster than humans, and the concordant call rate between humans and EVIDENCE was 97.72% (257/263). Additionally, EVIDENCE outperformed human accuracy, especially at discovering causative variants of rare syndromic deafness, whereas flexible interpretations that required predefined specific genotype-phenotype correlations were possible only by manual prioritization. The automated variant prioritization system remarkably facilitated the molecular diagnosis of hearing loss with high accuracy and efficiency, fostering the popularization of molecular genetic diagnosis of SNHL.

NO2-Affinitive Conjugated Polymer for Selective Sub-Parts-Per-Billion NO2 Detection in a Field-Effect Transistor Sensor.

Conjugated polymers (CPs) have provided versatile semiconducting implements for the development of soft electronic devices. When three CPs with the same conjugated framework but different side chains were adopted in the field-effect transistor (FET) sensor for NO2 detection, the response to NO2 showed an opposite tendency to the charge carrier mobility of each CP. Morphological and structural characterizations revealed that the flexible glycol side chain enhances NO2 affinity as well as prevents the formation of lamellar stacking of the CP chains, thereby providing routes for the facile diffusion of NO2. Additionally, theoretical calculations for CP-NO2 complex formation at the molecular level support the relatively low energy barrier for inter-chain transition of NO2 between the glycol-based conjugated frameworks, which implies the spontaneous internal diffusion of NO2 to the semiconductor-dielectric interface in the FET-based sensor. As a result, the CP with a NO2-affinitive morphology exhibited an exceptional sensitivity of 13.8%/ppb upon NO2 (100 ppb) exposure for 50 s and provided excellent selectivity to the FET-based sensor toward other environmentally abundant harmful gases, such as SO2, CO2, and NH3. In particular, the theoretic limit of detection reached down to 0.24 ppb, which is the lowest value ever reported for organic FET-based NO2 gas sensors.

Effective Dark Current Suppression for High-Detectivity Organic Near-Infrared Photodetectors Using a Non-Fullerene Acceptor.

Near-infrared organic photodetectors (NIR OPDs) have attracted considerable attention because of their inherent advantages such as a tailorable light absorption property, low-cost fabrication, compatibility with flexible substrates, and room-temperature operation. In particular, the development of NIR detection between 900 and 950 nm is crucial for noise-free communication in ambient environments. In this work, we demonstrate high-detectivity NIR OPDs at 900-950 nm by employing a non-fullerene acceptor (ITIC) used with an NIR-absorbing conjugated polymer (PNIR) for bulk heterojunction (BHJ), which significantly suppressed dark current. Systemic characterizations including electrical, structural, and morphological analyses revealed that ITIC effectively reduces charge recombination during the operation of the OPDs under NIR illumination, resulting in a dark current reduction and high detectivity of over 3.2 × 1011 Jones at 900-950 nm. The results presented here demonstrate that utilizing a non-fullerene acceptor for BHJ-type NIR OPDs is evidently a strategic approach for the simultaneous achievement of the low dark current and high-detectivity of NIR OPDs.

Otological aspects of NLRP3-related autoinflammatory disorder focusing on the responsiveness to anakinra.

OBJECTIVES: Gradually progressive sensorineural hearing loss (SNHL) is a prevalent sensory defect. It is generally untreatable, making rehabilitation by hearing aid or cochlear implantation the only option. However, SNHL as one of the symptoms of the hereditary autoinflammatory systemic disease cryopyrin-associated periodic syndrome, or as the only symptom of the cochlea-specific form (DFNA34), was suggested to respond to IL-1 antagonist (anakinra) therapy, which ameliorates NLRP3 variants-induced over-secretion of IL-1ß. We analysed genotypic and phenotypic spectrum of cryopyrin-associated periodic syndrome or DFNA34, specifically focusing on the responsiveness of SNHL to anakinra. METHODS: Seventeen families diagnosed with either cryopyrin-associated periodic syndrome or DFNA34 were recruited. Genotyping and phenotyping including audiogram, MRI findings, and in vitro IL-1ß assay were performed. RESULTS: Our cohort had an etiologic homogeneity of 94.1% to NLRP3 variants and a high de novo occurrence (84.6%). We identified the second DNFA34 pedigree worldwide with a novel NLRP3 variant supported by in vitro analysis. Significant improvement of hearing status against the natural course, showing response to anakinra, was identified in three probands, one of whom used to have severe SNHL. Hearing threshold worse than 60 dB at the start of anakinra and cochlear enhancement on brain MRI seemed to be related with poor audiologic prognosis and responsiveness to anakinra therapy despite stabilized systemic symptoms and inflammatory markers. CONCLUSION: We propose a constellation of biomarkers comprising NLRP3 genotypes, hearing status at diagnosis, and cochlear radiological findings as prognostic factors of hearing status after anakinra treatment and possibly as sensitive parameters for treatment dosage adjustment.

Improvement of Electrical Conductivity in Conjugated Polymers through Cascade Doping with Small-Molecular Dopants.

Doping capability is primitively governed by the energy level offset between the highest occupied molecular orbital (HOMO) of conjugated polymers (CPs) and the lowest unoccupied molecular orbital (LUMO) of dopants. A poor doping efficiency is obtained when doping directly using NOBF4 forming a large energy offset with the CP, while the devised doping strategy is found to significantly improve the doping efficiency (electrical conductivity) by sequentially treating the NOBF4 to the pre-doped CP with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquino-dimethane (F4TCNQ), establishing a relatively small energy level offset. It is verified that the cascade doping strategy requires receptive sites for each dopant to further improve the doping efficiency, and provides fast reaction kinetics energetically. An outstanding electrical conductivity (>610 S cm-1 ) is achieved through the optimization of the devised doping strategy, and spectroscopy analysis, including Hall effect measurement, supports more efficient charge carrier generation via the devised cascade doping.

Flexible Real-Time Polymerase Chain Reaction-Based Platforms for Detecting Deafness Mutations in Koreans: A Proposed Guideline for the Etiologic Diagnosis of Auditory Neuropathy Spectrum Disorder.

Routine application of next-generation sequencing in clinical settings is often limited by time- and cost-prohibitive complex filtering steps. Despite the previously introduced genotyping kit that allows screening of the 11 major recurring variants of sensorineural hearing loss (SNHL) genes in the Korean population, the demand for phenotype- and variant-specific screening kits still remains. Herein, we developed a new real-time PCR-based kit (U-TOP™ HL Genotyping Kit Ver2), comprising six variants from two auditory neuropathy spectrum disorder (ANSD) genes (OTOF and ATP1A3) and five variants from three SNHL genes (MPZL2, COCH, and TMC1), with a distinct auditory phenotype, making this the first genotyping kit dedicated to ANSD. The concordance rate with Sanger sequencing, sensitivity, and specificity of this genotyping kit were all 100%, suggesting reliability. The kit not only allows timely and cost-effective identification of recurring OTOF variants, but it also allows timely detection of cochlear nerve deficiency for those without OTOF variants. Herein, we provide a clinical guideline for an efficient, rapid, and cost-effective etiologic diagnosis of prelingual ANSD. Our study provides a good example of continuing to update new key genetic variants, which will continuously be revealed through NGS, as targets for the newly developed genotyping kit.

Novel genotype-phenotype correlation of functionally characterized LMX1A variants linked to sensorineural hearing loss.

LMX1A, encoding the LIM homeobox transcription factor, is essential for inner ear development. Despite previous reports of three human LMX1A variants with nonsyndromic hearing loss (NSHL) in the literature, functional characterization of these variants has never been performed. Encouraged by identification of a de novo, heterozygous, missense variant (c.595A > G; p.Arg199Gly) located in the homeodomain of LMX1A in a subject with congenital severe-to-profound deafness through Exome sequencing, we performed luciferase assay to evaluate transcriptional activity of all LMX1A variants reported in the literature including p.Arg199Gly. Resultantly, p.Arg199Gly manifesting the most severe NSHL showed the biggest reduction of transcriptional activity in contrast with moderately reduced activity of p.Cys97Ser and p.Val241Leu associated with less severe progressive NSHL, proposing a genotype-phenotype correlation. Further, our dominant LMX1A variant exerted pathogenic effects via haploinsufficiency rather than dominant-negative effect. Collectively, we provide a potential genotype-phenotype correlation of LMX1A variants as well as the pathogenic mechanism of LMX1A-related NSHL.

High Efficiency Doping of Conjugated Polymer for Investigation of Intercorrelation of Thermoelectric Effects with Electrical and Morphological Properties.

Intercorrelation of thermoelectric properties of a doped conjugated semiconducting polymer (PIDF-BT) with charge carrier density, conductive morphology, and crystallinity are systematically investigated. Upon being doped with F4-TCNQ by the sequential doping method, PIDF-BT exhibited a high electrical conductivity over 210 S cm-1. The significant enhancement of electrical conductivity resulted from a high charge carrier density, which is attributed to the effective charge-transfer-based integer doping between PIDF-BT and dopant molecules. Based on the systemic characterization on the optical, electrical, and structural properties of doped PIDF-BT annealed at different temperatures, we investigated the characteristic correlations between thermoelectric properties of PIDF-BT films and their four-probe electrical conductivity, charge carrier density, and charge carrier mobility obtained from AC Hall effect measurements. This study revealed that exercising fine control over the crystallinity and conductive migration of the conjugated polymer films can be a strategic approach to suppressing the degradation of the Seebeck coefficient at high charge carrier density and ultimately to maximizing the power factors of organic thermoelectric devices.

Korean Pharmacovigilance System Based on EHR-CDM.

An electronic health record (EHR) contains various clinical information for pharmacovigilance studies, but they remain difficult to use. From 2016 to 2018, the ministry of food and drug safety and Korea institute of drug safety & risk management (KIDS) converted the EHRs of more than 9 million patients to a MOA common data model (CDM). KIDS developed the Medical record observation and assessment for drug safety network (MOA-Net), a web portal site to build a network between CDM data partners. Through MOA-Net, hospitals participated in pharmacovigilance studies and confirmed the usability and adequacy of the CDM.