1.Advancing Natural Killer Cell Therapy: Genetic Engineering Strategies for Enhanced Cancer Immunotherapy
Joo Dong PARK ; Ha Eun SHIN ; Yeon Su AN ; Hye Jung JANG ; Juwon PARK ; Se-Na KIM ; Chun Gwon PARK ; Wooram PARK
Annals of Laboratory Medicine 2025;45(2):146-159
Natural killer (NK) cells are pivotal innate immune system components that exhibit spontaneous cytolytic activity against abnormal cells, such as infected and tumor cells. NK cells have shown significant promise in adoptive cell therapy because of their favorable safety profiles and minimal toxicity in clinical settings. Despite their advantages, the therapeutic application of unmodified NK cells faces challenges, including limited in vivo persistence, particularly in the immunosuppressive tumor microenvironment. Recent advances in genetic engineering have enhanced the therapeutic potential of NK cells by addressing these limitations and improving their therapeutic efficacy. In this review, we have described various methodologies for the genetic modification of NK cells, including viral vectors, electroporation, and nanoparticle-based approaches. The ongoing research on nanomaterialbased approaches highlights their potential to overcome current limitations in NK cell therapy, paving the way for advanced cancer therapy and improved clinical outcomes. In this review, we also emphasize the potential of engineered NK cells in cancer immunotherapy and other clinical applications, highlighting the expanding scope of NK cell-based treatments and the critical role of innovative genetic engineering techniques.
2.A single‑center outcome of choosing catheter ablation as the initial treatment in tachycardia–bradycardia syndrome and a new predictive factor for pacemaker implantation
Hye Ree KIM ; Juwon KIM ; Ju Youn KIM ; Seung‑Jung PARK ; Kyoung‑Min PARK ; Young Keun ON
International Journal of Arrhythmia 2024;25(4):20-
Background:
The relationship between sinus node dysfunction and atrial fibrillation (AF) has been well known. The reversibility of sinus node dysfunction is indeed a critical factor in determining the treatment strategy in patients with tachycardia–bradycardia syndrome (TBS). We aimed to assess the clinical outcome of choosing catheter abla‑ tion as the initial treatment in tachycardia–bradycardia syndrome and predictive factors leading to the implantation of a permanent pacemaker (PPM) in these patients.
Methods:
Patients with TBS who had been taken AF catheter ablation from 2012 to 2021 were reviewed, and 113 patients were enrolled. Patients were divided into two groups based on whether a “sinus pause episode of more than 3 s unrelated to tachyarrhythmia” coexists (Group I, n = 20) or not (Group II, n = 93).
Results:
Compared to Group II, baseline characteristics showed that Group I was comprised of more female gender (p = 0.043), with hypertension (p = 0.033), and with enlarged left atrium (p = 0.003). An average three-year follow-up found that eight patients (8/113, 7%) were implanted PPM (5/20, 25% in Group I vs. 3/93, 3.2% in Group II, p = 0.001).Using a multivariate model, a “sinus pause episode unrelated to tachyarrhythmia” was strongly associated with PPM implantation after catheter ablation in patients with TBS (HR 6.765, 95% CI 1.355–33.763, p = 0.020). Only four out of 113 patients (3.5%) progressed to persistent or permanent AF.
Conclusions
After catheter ablation as the initial treatment in TBS, only 7% underwent PPM implantation, and an iso‑ lated sinus pause was a predictive factor for requiring PPM implantation. In addition, even in patients who undergo catheter ablation with subsequent PPM implantation, we can expect to improve the clinical outcome associated with a reduced AF burden.
3.A single‑center outcome of choosing catheter ablation as the initial treatment in tachycardia–bradycardia syndrome and a new predictive factor for pacemaker implantation
Hye Ree KIM ; Juwon KIM ; Ju Youn KIM ; Seung‑Jung PARK ; Kyoung‑Min PARK ; Young Keun ON
International Journal of Arrhythmia 2024;25(4):20-
Background:
The relationship between sinus node dysfunction and atrial fibrillation (AF) has been well known. The reversibility of sinus node dysfunction is indeed a critical factor in determining the treatment strategy in patients with tachycardia–bradycardia syndrome (TBS). We aimed to assess the clinical outcome of choosing catheter abla‑ tion as the initial treatment in tachycardia–bradycardia syndrome and predictive factors leading to the implantation of a permanent pacemaker (PPM) in these patients.
Methods:
Patients with TBS who had been taken AF catheter ablation from 2012 to 2021 were reviewed, and 113 patients were enrolled. Patients were divided into two groups based on whether a “sinus pause episode of more than 3 s unrelated to tachyarrhythmia” coexists (Group I, n = 20) or not (Group II, n = 93).
Results:
Compared to Group II, baseline characteristics showed that Group I was comprised of more female gender (p = 0.043), with hypertension (p = 0.033), and with enlarged left atrium (p = 0.003). An average three-year follow-up found that eight patients (8/113, 7%) were implanted PPM (5/20, 25% in Group I vs. 3/93, 3.2% in Group II, p = 0.001).Using a multivariate model, a “sinus pause episode unrelated to tachyarrhythmia” was strongly associated with PPM implantation after catheter ablation in patients with TBS (HR 6.765, 95% CI 1.355–33.763, p = 0.020). Only four out of 113 patients (3.5%) progressed to persistent or permanent AF.
Conclusions
After catheter ablation as the initial treatment in TBS, only 7% underwent PPM implantation, and an iso‑ lated sinus pause was a predictive factor for requiring PPM implantation. In addition, even in patients who undergo catheter ablation with subsequent PPM implantation, we can expect to improve the clinical outcome associated with a reduced AF burden.
4.A single‑center outcome of choosing catheter ablation as the initial treatment in tachycardia–bradycardia syndrome and a new predictive factor for pacemaker implantation
Hye Ree KIM ; Juwon KIM ; Ju Youn KIM ; Seung‑Jung PARK ; Kyoung‑Min PARK ; Young Keun ON
International Journal of Arrhythmia 2024;25(4):20-
Background:
The relationship between sinus node dysfunction and atrial fibrillation (AF) has been well known. The reversibility of sinus node dysfunction is indeed a critical factor in determining the treatment strategy in patients with tachycardia–bradycardia syndrome (TBS). We aimed to assess the clinical outcome of choosing catheter abla‑ tion as the initial treatment in tachycardia–bradycardia syndrome and predictive factors leading to the implantation of a permanent pacemaker (PPM) in these patients.
Methods:
Patients with TBS who had been taken AF catheter ablation from 2012 to 2021 were reviewed, and 113 patients were enrolled. Patients were divided into two groups based on whether a “sinus pause episode of more than 3 s unrelated to tachyarrhythmia” coexists (Group I, n = 20) or not (Group II, n = 93).
Results:
Compared to Group II, baseline characteristics showed that Group I was comprised of more female gender (p = 0.043), with hypertension (p = 0.033), and with enlarged left atrium (p = 0.003). An average three-year follow-up found that eight patients (8/113, 7%) were implanted PPM (5/20, 25% in Group I vs. 3/93, 3.2% in Group II, p = 0.001).Using a multivariate model, a “sinus pause episode unrelated to tachyarrhythmia” was strongly associated with PPM implantation after catheter ablation in patients with TBS (HR 6.765, 95% CI 1.355–33.763, p = 0.020). Only four out of 113 patients (3.5%) progressed to persistent or permanent AF.
Conclusions
After catheter ablation as the initial treatment in TBS, only 7% underwent PPM implantation, and an iso‑ lated sinus pause was a predictive factor for requiring PPM implantation. In addition, even in patients who undergo catheter ablation with subsequent PPM implantation, we can expect to improve the clinical outcome associated with a reduced AF burden.
5.Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation
Ju Youn KIM ; Juwon KIM ; Seung-Jung PARK ; Kyoung-Min PARK ; June Soo KIM ; Sung-Hwan KIM ; Jaemin SHIM ; Eue Keun CHOI ; Dae-Hyeok KIM ; Il-Young OH ; Young Keun ON ;
Journal of Korean Medical Science 2024;39(8):e72-
Background:
In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice.
Methods:
This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment.
Results:
A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21–1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54–19.03), and composite outcomes (adjusted HR, 1.13;95% CI, 0.47–2.69) between the HDRR and LDRR groups.
Conclusion
This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients.
6.Optimal Dose of Edoxaban for Very Elderly Atrial Fibrillation Patients at High Risk of Bleeding: The LEDIOS Registry
Ju Youn KIM ; Juwon KIM ; Seung-Jung PARK ; Kyoung-Min PARK ; Sang-Jin HAN ; Dae Kyeong KIM ; Yae Min PARK ; Sung Ho LEE ; Jong Sung PARK ; Young Keun ON ;
Korean Circulation Journal 2024;54(7):398-406
Background and Objectives:
Optimal anticoagulation in very elderly patients is challenging due to the high risk of anticoagulant-induced bleeding. The aim of this study was to assess outcomes of on-label reduced-dose edoxaban (30 mg) in very elderly patients who had additional risk factors for bleeding.
Methods:
This was a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of on-label reduced-dose edoxaban in atrial fibrillation (AF) patients 80 years of age or older and who had more than 1 risk factor for bleeding.
Results:
A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study, and 586 (23.9%) were 80 years of age or older with additional risk factors for bleeding. Major bleeding events occurred frequently among very elderly AF patients who had additional bleeding risk factors compared to other patients (unadjusted hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.16–4.02); however, there were no significant differences in stroke incidence (HR, 1.86; 95% CI, 0.98–3.55). There were no significant differences for either factor after adjusting for age and sex (adjusted HR, 1.65; 95% CI, 0.75–3.62 for major bleeding; adjusted HR, 1.13; 95% CI, 0.51–2.50 for stroke).
Conclusions
In very elderly AF patients with comorbidities associated with greater risk of bleeding, the incidence of major bleeding events was significantly increased. In addition, risk of stroke showed tendency to increase in same population. Effective anticoagulation therapy might be important in these high-risk population, and close observation of bleeding events might also be required.
7.Exercise capacity and risk of incident atrial fibrillation in healthy adults
Ju Youn KIM ; Soo Jin CHO ; Juwon KIM ; Tae-Wan CHUNG ; Seung-Jung PARK ; Kyoung-Min PARK ; June Soo KIM ; Young Keun ON
The Korean Journal of Internal Medicine 2023;38(6):872-878
Background/Aims:
Atrial fibrillation (AF) is a common arrhythmia and is associated with cardiovascular morbidity and mortality. It is important to identify and control the modifiable risk factors of AF. We aimed to examine the association of exercise capacity with the risk of incident AF within 3 years in healthy subjects.
Methods:
We evaluated asymptomatic adults who had undergone more than two consecutive health checkups. We included subjects who exhibited normal sinus rhythm on the first health examination and who developed AF on the second or subsequent health examinations. Subjects who underwent cardiopulmonary exercise testing within 3 years before the diagnosis of AF were examined.
Results:
The study population in the analyses included 428 cases (mean age 58.4 ± 7.6 yr, male 95.6%). There were significant differences in maximal systolic blood pressure (SBP; case 169.4 ± 24.2 vs. control 173.9 ± 22.3 mmHg), peak VO2 (29.5 ± 5.4 vs. 30.4 ± 4.8 mL/kg per minute), and maximal metabolic equivalents (METs; 8.5 ± 1.6 vs. 8.7 ± 1.4) between the two groups. In the multivariable logistic models, adjusted odds ratios were 0.99 for maximal SBP (95% confidence interval [CI] 0.98–0.99), 0.97 for peak VO2 (95% CI 0.95–0.99), and 0.91 for maximal METs (95% CI 0.83–0.98).
Conclusions
We demonstrated that poorer exercise capacity was associated with the development of AF in a healthy population. A prospective, systematic trial is necessary to confirm that appropriate exercise training will be beneficial in preventing the development of AF in such patients.
8.Assessment of left atrial remodeling using speckle tracking echocardiography after percutaneous atrial septal defect closure in adult patients
Ji‑Hoon CHOI ; Ju Youn KIM ; Jin Kyung HWANG ; Hye Ree KIM ; Tae Wan CHUNG ; Juwon KIM ; Seung Woo PARK ; I‑Seok KANG ; Jinyoung SONG ; Seung‑Jung PARK ; Kyoung‑Min PARK ; Young Keun ON ; June Soo KIM ; June HUH
International Journal of Arrhythmia 2022;23(3):23-
Background:
Atrial fibrillation (AF) is a well-known, long-term complication of atrial septal defect (ASD) in adults, even after device closure. Left atrial (LA) strain rate applied to the analysis of chamber function has been demon‑ strated to be an important predictor of LA reverse remodeling. This study aimed to determine the changes in cham‑ ber function after device closure of ASD.
Methods:
This prospective study enrolled adults with secundum ASD undergoing transcatheter device closure from December 2016 to August 2017. We analyzed the clinical characteristics and LA strain rate before and six months after ASD closure.
Results:
A total of 11 patients were enrolled. The mean age was 42.6 ± 9.9 years, and six (54.5%) were females. There was no significant change of conventional echocardiographic parameters after ASD closure. The mean global LA res‑ ervoir strain rate before ASD closure was 1.17 ± 0.34 and 0.85 ± 0.30 after ASD closure (p = 0.030). The median global LA conduit strain rate was 0.68 (0.42–1.16) and 0.41 (0.16–0.79) before and after ASD closure (p = 0.213), respectively. The mean global LA contractile strain rate at the six-month follow-up showed significant improvement compared with pre-procedural strain rate (0.33 ± 0.65 vs. − 0.43 ± 0.38, p = 0.006).
Conclusions
LA functional changes occurred during the six-month follow-up, while LA and right atrial (RA) geo‑ metric changes were not significant. LA reverse remodeling was proved by restoration of LA late diastolic contractile function.
9.Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0
Sunho KIM ; Royoung KIM ; Ryeo-Gyeong KIM ; Enjin KO ; Han-Su KIM ; Jihye SHIN ; Daeun CHO ; Yurhee JIN ; Soyeon BAE ; Ye Won JO ; San Ah JEONG ; Yena KIM ; Seoyeon AHN ; Bomi JANG ; Jiheyon SEONG ; Yujin LEE ; Si Eun SEO ; Yujin KIM ; Ha-Jeong KIM ; Hyeji KIM ; Hye-Lynn SUNG ; Hyoyoung LHO ; Jaywon KOO ; Jion CHU ; Juwon LIM ; Youngju KIM ; Kyungyeon LEE ; Yuri LIM ; Meongeun KIM ; Seonjeong HWANG ; Shinhye HAN ; Sohyeun BAE ; Sua KIM ; Suhyeon YOO ; Yeonjeong SEO ; Yerim SHIN ; Yonsoo KIM ; You-Jung KO ; Jihee BAEK ; Hyejin HYUN ; Hyemin CHOI ; Ji-Hye OH ; Da-Young KIM ; Hee-Jo NAM ; Hyun-Seok PARK
Genomics & Informatics 2020;18(3):e33-
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.
10.Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0
Sunho KIM ; Royoung KIM ; Ryeo-Gyeong KIM ; Enjin KO ; Han-Su KIM ; Jihye SHIN ; Daeun CHO ; Yurhee JIN ; Soyeon BAE ; Ye Won JO ; San Ah JEONG ; Yena KIM ; Seoyeon AHN ; Bomi JANG ; Jiheyon SEONG ; Yujin LEE ; Si Eun SEO ; Yujin KIM ; Ha-Jeong KIM ; Hyeji KIM ; Hye-Lynn SUNG ; Hyoyoung LHO ; Jaywon KOO ; Jion CHU ; Juwon LIM ; Youngju KIM ; Kyungyeon LEE ; Yuri LIM ; Meongeun KIM ; Seonjeong HWANG ; Shinhye HAN ; Sohyeun BAE ; Sua KIM ; Suhyeon YOO ; Yeonjeong SEO ; Yerim SHIN ; Yonsoo KIM ; You-Jung KO ; Jihee BAEK ; Hyejin HYUN ; Hyemin CHOI ; Ji-Hye OH ; Da-Young KIM ; Hee-Jo NAM ; Hyun-Seok PARK
Genomics & Informatics 2020;18(3):e33-
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.

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