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Wonnam Kim,1,* Yeon-Cheol Park,2,3,* Bonhyuk Goo,2 Jung-Hyun Kim,2 Dongwoo Nam,3,4 Eunseok Kim,5,6 Hyun-Jong Lee,7 Dong-Hyun Pyun,8,9 Hae Sun Suh,8– 10 Yoonsung Lee,11 Man S Kim,11 Byung-Kwan Seo,2,3 Yong-Hyeon Baek2,3 1Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 2Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 3Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 4Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 5Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 6Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 7Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 8Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea; 9Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul, Republic of Korea; 10College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; 11Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Yong-Hyeon Baek, Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea, Tel +82 2 440 6099, Fax +82 2 440 714, Email byhacu@khu.ac.krPurpose: Knee osteoarthritis (KOA) is one of the most prevalent degenerative joint diseases worldwide. The herbal decoction, Dokhwalgisaeng-tang (DHGST), has been commonly used in East Asia to treat osteoarthritis. However, there is insufficient evidence to draw clear conclusions concerning its effectiveness and safety for patients with KOA. We aim to determine the efficacy, safety, and economic feasibility of DHGST compared with Celecoxib, an oral COX-2 inhibitor, for patients with degenerative KOA.Trial Design and Methods: This multicenter, randomized, noninferiority trial, involving 160 participants who will be randomized using block randomization with 1:1 allocation, will compare DHGST and Celecoxib. The total trial period is 24 weeks after random allocation, comprising 12 weeks of treatment and 12 weeks of follow-up. Participants with KOA will be administered 200 mg of DHGST (treatment group) or Celecoxib capsules (control group) for 12 weeks. Efficacy and safety evaluations will be conducted at weeks 0, 4, 8, and 12, and 24. The primary outcome measurement is the Korean Western Ontario McMaster score at week 12. Changes in pain intensity using a 100 mm visual analog scale, changes in quality of life using a EuroQol 5-dimension 5-level self-report survey, and patient satisfaction will also be measured to evaluate effectiveness between the two groups. A trial-based economic feasibility evaluation will be conducted to analyze treatment cost-effectiveness from societal and healthcare system perspectives. Drug safety will be assessed through adverse reactions and laboratory test findings.Discussion: This trial protocol has the following limitations. Applying a double-dummy design is not possible, as the tablet and granule forms can easily be distinguished visually, and achieving participant blinding is challenging. The trial findings are intended to inform participants, physicians, and other stakeholders in determining whether DHGST could be used as an alternative therapeutic option for KOA.Trial Registration Number: KCT0008424 (Clinical Research Information Service of the Republic of Korea), registered on 12 May 2023.Keywords: degenerative joint disease, Dokhwalgisaeng-tang, noninferiority trial, randomized controlled trial

Bonhyuk Goo,1,* Yeon-Cheol Park,2,* Eunseok Kim,3,4 Won-Suk Sung,5 Eun-Jung Kim,6 Jung-Hyun Kim,1 Byung-Kwan Seo,2 Yong-Hyeon Baek2 1Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 2Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 3Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 4Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan-si, Republic of Korea; 5Department of Acupuncture & Moxibustion, Dongguk University Bundang Oriental Hospital, Seongnam, Republic of Korea; 6Department of Acupuncture & Moxibustion Medicine, College of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea*These authors contributed equally to this workCorrespondence: Yong-Hyeon Baek, Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea, Tel +82 2 440 6099, Fax +82 2 440 7143, Email byhacu@khu.ac.krBackground: The aim of the present study is to confirm the efficacy, safety, and cost-effectiveness of thread-embedding acupuncture (TEA) in the treatment of adhesive capsulitis (AC).Methods: This is a randomized, sham-controlled, patient-assessor blinded trial with two parallel arms in a 1:1 ratio. A total of 160 participants with AC, also known as frozen shoulder, will be recruited and screened according to the eligibility criteria. Those who meet the eligibility criteria will be randomly allocated to a TEA group or a sham TEA (STEA) group. Both groups will receive either real TEA or thread-removed STEA treatment on nine acupoints once a week for 8 weeks while being blinded to the intervention. The shoulder pain and disability index will be evaluated as a primary outcome measure. In addition, a 100-mm pain visual analogue scale, rotator cuff quality of life scale, European Quality of Life 5-dimension 5-level scale, treatment satisfaction, safety assessment, and economic evaluation will be assessed as secondary outcome measures. Outcome assessments will be conducted for a total of 24 weeks, including a treatment period of 8 weeks and follow-up of 16 weeks, according to the schedule.Discussion: The results of this trial will provide a clinical basis for the efficacy, safety and cost-effectiveness of TEA in the treatment of patients with AC.Trial Registration Number: KCT0005920 (Clinical Research Information Service of the Republic of Korea). Registered on 22 February 2021.Keywords: thread-embedding acupuncture, adhesive capsulitis, frozen shoulder, randomized controlled trial, protocol

Su Eun Lim,* Ho Seok Kim,* Si Woo Lee, Kwang-Ho Bae, Young Hwa Baek KM Data Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea*These authors contributed equally to this workCorrespondence: Young Hwa Baek, KM Data Division Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea, Tel +82 10-2555-2138, Email aori79@kiom.re.krPurpose: The commercialization of sleep activity tracking devices has made it possible to manage sleep quality at home. However, it is necessary to verify the reliability and accuracy of wearable devices through comparison with polysomnography (PSG), which is the standard for tracking sleep activity. This study aimed to monitor overall sleep activity using Fitbit Inspire 2™ (FBI2) and to evaluate its performance and effectiveness through PSG under the same conditions.Patients and Methods: We compared the FBI2 and PSG data of nine participants (four male and five female participants; average age, 39 years) without severe sleeping problems. The participants wore FBI2 continuously for 14 days, considering the period of adaptation to the device. FBI2 and PSG sleep data were compared using paired t-tests, Bland–Altman plots, and epoch-by-epoch analysis for 18 samples by pooling data from two replicates.Results: The average values for each sleep stage obtained from FBI2 and PSG showed significant differences in the total sleep time (TST), deep sleep, and rapid eye motion (REM). In the Bland–Altman analysis, TST (P = 0.02), deep sleep (P = 0.05), and REM (P = 0.03) were significantly overstated in FBI2 compared to PSG. In addition, time in bed, sleep efficiency, and wake after sleep onset were overestimated, while light sleep was underestimated. However, these differences were not statistically significant. FBI2 showed a high sensitivity (93.9%) and low specificity (13.1%), with an accuracy of 76%. The sensitivity and specificity of each sleep stage was 54.3% and 62.3%, respectively, for light sleep, 84.8% and 50.1%, respectively, for deep sleep, and 86.4% and 59.1%, respectively for REM sleep.Conclusion: The use of FBI2 as an objective tool for measuring sleep in daily life can be considered appropriate. However, further research is warranted on its application in participants with sleep-wake problems.Keywords: wearable, sleep, tracking, polysomnography, validation study

Hyung Joon Yim,1,&ast; Ji Hoon Kim,2,&ast; Yong Kyun Cho,3 Young Oh Kweon,4 Hyun Chin Cho,5 Jae Seok Hwang,6 Changhyeong Lee,7 Moon Soo Koh,8 Yang-Hyun Baek,9 Young-Min Park,10 Jeong-Hoon Lee,11 Seung Up Kim,12 Min-Kyu Kang,13 Neung Hwa Park,14 June Sung Lee,15 Young Eun Chon,16 Gab Jin Cheon,17 Hee Bok Chae,18 Joo Hyun Sohn,19 Young-Suk Lim20 1Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Korea; 2Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; 3Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea; 5Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea; 6Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea; 7Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea; 8Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Dongguk University, Goyang, Korea; 9Department of Gastroenterology, DongA University College of Medicine, Busan, Korea; 10Department of Internal Medicine, Bundang Jesaeng General Hospital, Seongnam, Korea and Hepatology Center, Bundang Jesaeng General Hospital, Seongnam, Korea; 11Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea; 12Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, and Yonsei Liver Center, Severance Hospital, Seoul, Korea; 13Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea; 14Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea; 15Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea; 16Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 17Department of Medicine, GangNeung Asan Hospital, Ulsan University College of Medicine, Gangwon-do, Korea; 18Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea; 19Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea, and Hanyang University Guri Hospital, Guri, Korea; 20Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Young-Suk Lim, Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 43-Gil 88, Olympic-Ro, Songpa-Gu, Seoul, Korea, Tel +82-2-3010-3190, Fax +82-2-485-5782, Email limys@amc.seoul.krPurpose: Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet’s size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB).Patients and Methods: CHB patients with HBV-DNA < 69 IU/mL after ≥ 24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA < 69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities.Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was − 2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; − 0.8 ± 9.8 versus − 2.4 ± 12.8 mL/min, respectively (P=0.017).Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.Keywords: viral DNA, bone density, antiviral agents, viral suppression

Bonhyuk Goo,1 Yong-Hyeon Baek2 1Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, Republic of Korea; 2Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of KoreaCorrespondence: Yong-Hyeon BaekDepartment of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of KoreaTel +82 2 440 6099Fax +82 2 440 7143Email byhacu@khu.ac.krPurpose: This study aims to determine the feasibility of thread-embedding acupuncture (TEA) for the treatment of shoulder instability.Patients and Methods: This is a patient-assessor blinded, randomized, sham-controlled trial with two parallel arms. A total of 40 patients with shoulder instability aged between 13 and 43 years will be recruited and screened using set inclusion and exclusion criteria. After screening, they will be randomly allocated to the TEA or sham TEA group. Patients in both groups will then receive TEA or sham TEA treatment on six acupoints once a week for 8 weeks, which will be followed by additional follow-up assessments at 4 and 8 weeks after the end of treatment. Changes in shoulder pain and disability will be assessed as the primary outcome, whereas 100-mm pain visual analogue scale, shoulder range of motion, rotator cuff quality of life index, EuroQol 5-dimension 5-levels, treatment satisfaction, economic evaluation, and safety will all be measured as secondary outcomes of the study. Outcome assessment will be conducted at baseline and at 4, 8, and 16 weeks after screening.Conclusion: The results from this trial will help to design further clinical trials on the efficacy, safety, and cost-effectiveness of performing TEA for shoulder instability.Trial Registration Number: KCT0005921 (Clinical Research Information Service of the Republic of Korea).Keywords: thread-embedding acupuncture, shoulder instability, shoulder pain, pilot study, randomized controlled trial

Yeon-Cheol Park,1,* Bon-Hyuk Goo,2,* Kyeong-Ju Park,3 Jun-Yeon Kim,3 Yong-Hyeon Baek1 1Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, 02447, South Korea; 2Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, Seoul, 05278, South Korea; 3Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, South Korea*These authors contributed equally to this workCorrespondence: Yong-Hyeon BaekDepartment of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, South KoreaTel +82 02 440 8642Fax +82 02 440 7770Email byhacu@khu.ac.krBackground: Knee osteoarthritis (OA) is a degenerative disease of the joint cartilage with no definite treatment in the early stage. Several previous review studies have shown that alternative medical treatments, including acupuncture, moxibustion, and herbal medicines, are effective in improving the symptoms of the disease and the patient’s quality of life. However, no systematic review study has shown the effectiveness of the combination of conventional and alternative therapies. Therefore, the aim of our study is to determine the most effective combination therapies and to provide evidence for the effectiveness and safety of integrated therapies. This article describes the protocol for the methods that will be applied in our systematic review.Methods: We will conduct an electronic search of nine databases: PubMed, Embase, Cochrane, Google Scholar (first 100 articles), four Korean databases (KoreaMed, Korean Studies Information Service System, Research Information Service System, and Oriental Medicine Advanced Searching Integrated System), and one Chinese database (China National Knowledge Infrastructure). Only randomized controlled studies that reported on both conventional treatment (drugs and hyaluronic acid) and traditional Korean medicine (acupuncture, moxibustion, and herbal medicines) will be selected. The primary outcomes will be pain and function of the joint. The secondary outcomes will include pain relief duration, total effective rate, incidence of adverse events, and quality of life. We will assess the methodological quality of the included studies using the Cochrane risk of bias tool. For the meta-analysis, standardized mean differences and risk ratios with 95% confidence intervals will be applied for continuous and dichotomous data, respectively.Results: This review will evaluate the effectiveness and safety of several Korean medicine treatments combined with conventional treatments for knee OA.Conclusion: Our review will provide a good foundation for the integrative treatment of knee OA.Keywords: acupuncture, herbal medicine, hyaluronic acid injection, knee osteoarthritis, moxibustion, NSAIDs

This study is a double-blind randomized controlled trial on the effect of intradermal acupuncture on insomnia after stroke. Hospitalized stroke patients with insomnia were enrolled in the study and were randomly assigned to either a real intradermal acupuncture group (RA group) or a sham acupuncture group (SA group). The RA group received intradermal acupuncture on Shen-Men (He-7) and Nei-Kuan (EH-6) for three days, and the SA group received sham acupuncture on the same points. The effect of acupuncture on insomnia was measured using Insomnia Severity Index (ISI) and Athens Insomnia Scale (AIS) at baseline and three days after treatment. To assess the effect of acupuncture on the autonomic nervous function, the subjects' blood pressure and heart rate variability were monitored. Fifty-two subjects (27 in the RA group and 25 in the SA group) were included in the final analysis. The insomnia-related scales ISI and AIS showed greater improvement of insomnia in the RA group than in the SA group. Moreover, there is a greater reduction of the number of non-dippers and a greater decrease of the LF/HF ratio (heart rate variability) in the RA group than in the SA group. These results indicate that sympathetic hyperactivities were stabilized in the RA group. It can thus be concluded that intradermal acupuncture on Shen-Men and Nei-Kuan is a useful therapeutic method for post stroke-onset insomnia as it reduces sympathetic hyperactivities. [ABSTRACT FROM AUTHOR]

Understanding the mammalian pathogenesis and interspecies transmission of HPAI H5N8 virus hinges on mapping its adaptive markers. We used deep sequencing to track these markers over five passages in murine lung tissue. Subsequently, we evaluated the growth, selection, and RNA load of eight recombinant viruses with mammalian adaptive markers. By leveraging an integrated non-linear regression model, we quantitatively determined the influence of these markers on growth, adaptation, and RNA expression in mammalian hosts. Furthermore, our findings revealed that the interplay of these markers can lead to synergistic, additive, or antagonistic effects when combined. The elucidation distance method then transformed these results into distinct values, facilitating the derivation of a risk score for each marker. In vivo tests affirmed the accuracy of scores. As more mutations were incorporated, the overall risk score of virus heightened, and the optimal interplay between markers became essential for risk augmentation. Our study provides a robust model to assess risk from adaptive markers of HPAI H5N8, guiding strategies against future influenza threats.

Background: Conflicting evidence exists regarding the effects of ursodeoxycholic acid (UDCA) on coronavirus disease 2019 (COVID-19). This study investigates the association between UDCA administration and COVID-19 infection and its related outcomes in individuals with chronic liver disease (CLD)., Methods: A customized COVID-19 research database (n = 3,485,376) was created by integrating data from the National Health Insurance Service (NHIS) and the Korea Disease Control and Prevention Agency's COVID-19 databases. The study focused on patients diagnosed with COVID-19 in 2021, using the NHIS data from 365 days before diagnosis. To create comparable groups with and without UDCA administration before COVID-19, we used propensity score matching. The primary endpoint was the first confirmed positive result for severe acute respiratory syndrome coronavirus-2. In addition, we identified severe COVID-19-related outcomes. Subgroup analysis were conducted based on the dose of UDCA exposure., Results: Data from 74,074 individuals with CLD was analyzed. The participants' average age was 57.5 years, and 52.1% (19,277) of those in each group were male. Those with prior UDCA exposure had a significantly lower risk of COVID-19 infection (adjusted OR: 0.80, 95% CI [0.76-0.85]) compared to the non-UDCA group. Additionally, the UDCA group had a lower risk of severe COVID-19 outcomes (adjusted OR: 0.67, 95% CI [0.46-0.98]). Subgroup analyses indicated that there was a decrease in COVID-19 infection and its related outcomes with increasing UDCA exposure dose., Conclusions: Our large observational study highlights the potential use of readily available UDCA as an adjunctive therapy for COVID-19 in individuals with CLD., (© 2024. The Author(s).)

Background: Although several studies have demonstrated a bidirectional relationship between nonalcoholic fatty liver disease (NAFLD) and chronic periodontitis, few studies have reported that NAFLD causes chronic periodontitis, especially in the Asian population., Methods: This study was conducted on 129,087 individuals, and the NAFLD score was assessed using the Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), and Framingham Steatosis Index (FSI). The incidence of chronic periodontitis was defined as a diagnostic code with dental procedures. Multi-variable adjusted Cox proportional hazard regression analysis was performed with hazard ratio (HR) and 95% confidence intervals (CIs)., Results: Nine thousand one hundred and twenty-eight chronic periodontitis cases (7.1%) were identified during a mean 7.4 years follow-up period. Each NAFLD score was related to chronic periodontitis. In the FLI score, HR and 95% CIs for the incidence of chronic periodontitis compared with a low FLI group were as follows: indeterminate FLI: 1.19 (1.12-1.26), high FLI: 1.32 (1.18-1.47). In the HSI and FSI scores, HR and 95% CIs for the incidence of chronic periodontitis were 1.13 (1.05-1.22) and 1.23 (1.05-1.31), respectively., Conclusions: All NAFLD scores were associated with chronic periodontitis in the Korean population. As chronic periodontitis can aggravate the liver status, patients with NAFLD may need regular dental visits., (© 2024 American Academy of Periodontology.)

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients., Aim: This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis., Methods: This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score., Results: ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH., Conclusions: In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD.

Background/aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression., Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD., Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort., Conclusion: We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Background/aims: Noninvasive methods have become increasingly critical in the diagnosis of fibrosis in chronic liver diseases. Herein, we compared the diagnostic performance of serum Mac2 binding protein glycosylation isomer (M2BPGi) and other serological panels for fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and proposed an improved two-step diagnostic algorithm for advanced fibrosis., Methods: We enrolled 231 patients diagnosed with NAFLD who underwent a liver biopsy. We subsequently evaluated the diagnostic performance of serological panels, including serum M2BPGi, a fibrosis index based on four factors (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), in predicting the stage of liver fibrosis. We then constructed a two-step algorithm to better differentiate advanced fibrosis., Results: The areas under the receiver operating characteristic curves of serum M2BPGi, FIB-4, APRI, and NFS for advanced fibrosis (≥F3) were 0.823, 0.858, 0.779, and 0.827, respectively. To reduce the performance of unnecessary liver biopsy, we propose a two-step algorithm using FIB-4 as an initial diagnostic tool and serum M2BPGi (≥0.6) as an additional diagnostic method for patients classified as intermediate (23%). Using the proposed algorithm, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.812, 0.814, 0.814, 0.600, and 0.927, respectively., Conclusions: Serum M2BPGi is a simple and effective test for advanced fibrosis in patients with NAFLD. Application of the two-step algorithm based on FIB-4 and M2BPGi proposed here can improve diagnostic performance and reduce unnecessary tests, making diagnosis easily accessible, especially in primary medical centers.

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad and continuous spectrum of liver diseases ranging from fatty liver to steatohepatitis. The intricate interactions of genetic, epigenetic, and environmental factors in the development and progression of MASLD remain elusive. Here, we aimed to achieve an integrative understanding of the genomic and transcriptomic alterations throughout the progression of MASLD., Approach and Results: RNA-Seq profiling (n = 146) and whole-exome sequencing (n = 132) of MASLD liver tissue samples identified 3 transcriptomic subtypes (G1-G3) of MASLD, which were characterized by stepwise pathological and molecular progression of the disease. Macrophage-driven inflammatory activities were identified as a key feature for differentiating these subtypes. This subtype-discriminating macrophage interplay was significantly associated with both the expression and genetic variation of the dsDNA sensor IFI16 (rs6940, A>T, T779S), establishing it as a fundamental molecular factor in MASLD progression. The in vitro dsDNA-IFI16 binding experiments and structural modeling revealed that the IFI16 variant exhibited increased stability and stronger dsDNA binding affinity compared to the wild-type. Further downstream investigation suggested that the IFI16 variant exacerbated DNA sensing-mediated inflammatory signals through mitochondrial dysfunction-related signaling of the IFI16-PYCARD-CASP1 pathway., Conclusions: This study unveils a comprehensive understanding of MASLD progression through transcriptomic classification, highlighting the crucial roles of IFI16 variants. Targeting the IFI16-PYCARD-CASP1 pathway may pave the way for the development of novel diagnostics and therapeutics for MASLD., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Objective: To describe the epidemiology, clinical characteristics and utilisation patterns of bone-targeting agents (BTAs) in patients with bone metastases from breast, prostate and lung cancer., Methods: This is a multinational retrospective cohort study including patients with three major solid tumours (breast, prostate and lung cancer) and newly initiated on BTAs (ie, denosumab, zoledronic acid and pamidronate). Records were retrieved from nationwide health databases from Hong Kong and Taiwan (HK and TW: 2013-2017) and Korea (KR: 2012-2016). Descriptive analyses included the annual incidence rates of bone metastases and the cumulative incidence curves of BTA initiation. We used Sankey diagrams to visualise the dynamic BTA utilisation patterns., Results: The annual incidence rate of bone metastases ranged from 3.5% to 4.5% in TW, from 9.6% to 10.3% in HK and from 2.9% to 3.8% in KR. We identified 14.1% (5127), 9.3% (883) and 9.4% (4800) of patients with bone metastases newly initiated on BTAs in TW, HK and KR, respectively. The most frequently used BTA in TW (67.1%) and HK (51.9%) was denosumab, while in KR (84.8%) it was zoledronic acid. Sankey diagrams indicated the proportion of patients remaining on denosumab was highest in TW and HK, while it was zoledronic acid in KR. Specifically, in TW, patients who were on bisphosphonates or had discontinued treatment frequently switched to or reinitiated denosumab., Conclusions: We found the rate of BTA utilisation remained low across all sites and tumour types in recent years. The dynamic utilisation patterns of BTAs provide better understanding of the treatment landscape for future evaluation of associated outcomes of patients., Competing Interests: Competing interests: C-LC reports receipt of funding from Amgen and Abbott, outside the submitted work. J-YS reports receipt of research funding from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, and the National Research Foundation of the Republic of Korea, and grants from pharmaceutical companies including Amgen, Pfizer, Hoffmann-La Roche, Dong-A ST and Yungjin, outside the submitted work. EC-CL reports receipt of research funding from the Ministry of Science and Technology and the Ministry of Health and Welfare of Taiwan, and grants from pharmaceutical companies including Amgen and Takeda, outside the submitted work. Amgen Asia Holdings was the affiliation of NJK at the time of conduct of the study., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea. Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea. Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n = 511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration ( p  < 0.001). Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea. Clinical trial registration: ClinicalTrials.gov NCT05225207.

Single-target rapid antigen tests (RATs) are commonly used to detect highly transmissible respiratory viruses (RVs), such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses. The simultaneous detection of RVs presenting overlapping symptoms is vital in making appropriate decisions about treatment, isolation, and resource utilization; however, few studies have evaluated multiplex RATs for SARS-CoV-2 and other RVs. We assessed the diagnostic performance of multiplex RATs targeting both the SARS-CoV-2 and influenza A/B viruses with the GenBody Influenza/COVID-19 Ag Triple, InstaView COVID-19/Flu Ag Combo (InstaView), STANDARD TM Q COVID-19 Ag Test, and STANDARD TM Q Influenza A/B Test kits using 974 nasopharyngeal swab samples. The cycle threshold values obtained from the real-time reverse transcription polymerase chain reaction results showed higher sensitivity (72.7-100%) when the values were below, rather than above, the cut-off values. The InstaView kit exhibited significantly higher positivity rates (80.21% for SARS-CoV-2, 61.75% for influenza A, and 46.15% for influenza B) and cut-off values (25.57 for SARS-CoV-2, 21.19 for influenza A, and 22.35 for influenza B) than the other two kits, and was able to detect SARS-CoV-2 Omicron subvariants. Therefore, the InstaView kit is the best choice for routine screening for both SARS-CoV-2 and influenza A/B in local communities.

Introduction: Although most patients with alcohol-related liver disease (ALD) have a history of prolonged and heavy drinking, there is no clear threshold defining the level of alcohol consumption that leads to ALD. We aimed to evaluate the correlation between average alcohol consumption and the risk of liver disease and to determine the threshold for clinically significant alcohol consumption., Materials and Methods: Using the Korean National Health Insurance database, we identified participants who underwent a health-screening program in 2010 and 2011 and retrospectively analyzed their data until 2019. To diagnose and categorize the extracted participants, we used the International Classification of Diseases version 10 and Fatty Liver Index. The primary outcome was to determine the incidence of newly diagnosed liver-related diseases during the observation period and compare the incidence of liver-related diseases among non-drinkers and drinkers based on the amount of alcohol consumption., Results: A total of 53,006 patients were enrolled and followed-up for a median of 8.4 years, during which 1,509 cases of liver-related diseases occurred. The participants were divided into five groups: no alcohol consumption ( n  = 31,359), 1st quartile ( n  = 5,242), 2nd quartile ( n  = 5,704), 3rd quartile ( n  = 5,337), and 4th quartile ( n  = 5,364). The corresponding number of glasses of alcohol consumed per week for each quantile (Q1, Q2, Q3, and Q4) was labeled 2.5 ± 1.1 standard units (1 standard unit = 8 g alcohol), 5.4 ± 1.9 standard units, 11.5 ± 3.3 standard units, and 27.9 ± 18.2 standard units, respectively. Compared with non-drinkers, the risk of liver-related disease was found to be higher in Q1 drinkers (adjusted hazard ratio [aHR], 1.09; 95% CI, 0.90-1.33), Q2 drinkers (aHR, 1. 10; 95% CI, 0.91-1.32), Q3 drinkers (aHR, 1.33; 95% CI, 1.11-1.59), and Q4 drinkers (aHR, 1.47; 95% CI, 1.24-1.75)., Conclusion: We report that our study has shown that drinking more than 11.5 ± 3.3 standard units/week (92 ± 26.4 g/week) significantly increases the risk of developing liver-related diseases. Therefore, as a preventive measure to reduce the risk of developing liver disease, alcohol consumption should be limited beyond traditionally recommended levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Moon, Son, Kang, Koh, Lee and Baek.)

Hepatic iron overload (HIO) is a hallmark of nonalcoholic fatty liver disease (NAFLD) with a poor prognosis. Recently, the role of hepatic erythrophagocytosis in NAFLD is emerging as a cause of HIO. We undertook various assays using human NAFLD patient pathology samples and an in vivo nonalcoholic steatohepatitis (NASH) mouse model named STAM TM . To make the in vitro conditions comparable to those of the in vivo NASH model, red blood cells (RBCs) and platelets were suspended and subjected to metabolic and inflammatory stresses. An insert-coculture system, in which activated THP-1 cells and RBCs are separated from HepG2 cells by a porous membrane, was also employed. Through various analyses in this study, the effect of cilostazol was examined. The NAFLD activity score, including steatosis, ballooning degeneration, inflammation, and fibrosis, was increased in STAM TM mice. Importantly, hemolysis occurred in the serum of STAM TM mice. Although cilostazol did not improve lipid or glucose profiles, it ameliorated hepatic steatosis and inflammation in STAM TM mice. Platelets (PLTs) played an important role in increasing erythrophagocytosis in the NASH liver. Upregulated erythrophagocytosis drives cells into ferroptosis, resulting in liver cell death. Cilostazol inhibited the augmentation of PLT and RBC accumulation. Cilostazol prevented the PLT-induced increase in ectopic erythrophagocytosis in in vivo and in vitro NASH models. Cilostazol attenuated ferroptosis of hepatocytes and phagocytosis of RBCs by THP-1 cells. Augmentation of hepatic erythrophagocytosis by activated platelets in NASH exacerbates HIO. Cilostazol prevents ectopic erythrophagocytosis, mitigating HIO-mediated ferroptosis in NASH models.

Although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern (PHEIC), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a vast impact to date. Hence, continuous management is required, given the uncertainty caused by the potential evolution of SARS-CoV-2. Reverse transcription-quantitative PCR (RT-qPCR) diagnosis has been fundamental in overcoming this issue. In this study, the performances of two rapid RT-qPCR assays (Real-Q Direct SARS-CoV-2 Detection Kit and Allplex™ SARS-CoV-2 fast PCR Assay) with short PCR times were comparatively evaluated using a STANDARD M nCoV Real-Time Detection Kit (STANDARD M, conventional RT-qPCR assay). All kits showed a limit of detection values (10 2 -10 3 copies/reaction). The evaluation showed that the two rapid assay tests had ≥97.89% sensitivity and ≥99.51% specificity (κ = 0.98) for individual samples and ≥97.32% sensitivity and ≥97.67% specificity for pooled samples compared to STANDARD M. These results indicate that the two rapid RT-qPCR kits, which showed significant time reduction in performance, are as effective as a conventional RT-qPCR assay. They are likely to increase not only the number of tests that can be performed but also the efficiency of sustainable management of COVID-19 in the long term.

Even though the World Health Organization announced the end of the COVID-19 pandemic as a global public health emergency on May 5, 2023, SARS-CoV-2 continues to pose a significant health threat worldwide, resulting in substantial numbers of infections and fatalities. This study investigated the antiviral potential of Z-FA-FMK (FMK), a novel host cathepsin L protease inhibitor, against SARS-CoV-2 infection using both in vitro and in vivo models. In vitro assessments of FMK against a diverse set of SARS-CoV-2 strains, including the Wuhan-like strain and nine variants, demonstrated potent inhibition with EC 50 values ranging from 0.55 to 2.41 μM, showcasing similar or superior efficacy compared to FDA-approved antivirals nirmatrelvir (NTV) and molnupiravir (MPV). In vivo experiments using orally administered FMK (25 mg/kg) in SARS-CoV-2-infected K18 hACE2 transgenic mice revealed improved survival rates of 60% and accelerated recovery compared to NTV and MPV treatments. Additionally, FMK displayed a longer half-life (17.26 ± 8.89 h) than NTV and MPV in the mouse model. Due to its host-targeting mechanism, FMK offers potential advantages such as reduced drug resistance and broad-spectrum antiviral activity against multiple coronaviruses. These findings indicate that FMK may serve as a promising candidate for further clinical evaluation in the fight against SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: We aimed to evaluate the effectiveness and safety of oriental medicine (OM) treatments as monotherapy and add-on therapy compared to conventional treatments for knee osteoarthritis and assess the quality of evidence for these results. OM treatment included acupuncture, herbal medicine, pharmacoacupuncture, and moxibustion., Methods: PubMed, Embase, Cochrane, Google Scholar, 4 Korean medical databases (KoreaMed, Korean Studies Information Service System, Research Information Service System, and Oriental Medicine Advanced Searching Integrated System), and one Chinese database (China National Knowledge Infrastructure) were searched for articles published between January 1, 2000, and January 1, 2021. Randomized controlled trials (RCTs) investigating the effect of OM interventions, single or combined with conventional treatments, on knee osteoarthritis were searched. The risk of bias and quality of evidence of the included studies were evaluated using the Cochrane Collaboration's risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation methods, respectively., Results: A total of 3911 relevant studies were retrieved and only 23 studies were included for systematic review. Most of the studies showed a significant effect on knee osteoarthritis. 21 studies comparing single OM treatment with conventional treatment were included in the meta-analysis. The effect size of standardized mean difference (SMD) was analyzed as a "small effect" with 0.48 (95% CI -0.80 to -0.16, Z = 2.98, P = .003). In addition, a meta-analysis of 4 studies comparing integrative treatment with conventional treatment showed a "very large effect" with 1.52 (95% CI -2.09 to -0.95, Z = 5.19, P < .001)., Conclusion: Our results suggest that single OM treatment and integrative treatment significantly reduce pain in patients with knee osteoarthritis. However, there is a limited number of RCTs considering integrative treatment which implies more related RCTs should be conducted in the future., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The appearance of SARS-CoV-2 variants in late 2020 raised alarming global public health concerns. Despite continued scientific progress, the genetic profiles of these variants bring changes in viral properties that threaten vaccine efficacy. Thus, it is critically important to investigate the biologic profiles and significance of these evolving variants. In this study, we demonstrate the application of circular polymerase extension cloning (CPEC) to the generation of full-length clones of SARS-CoV-2. We report that, combined with a specific primer design scheme, this yields a simpler, uncomplicated, and versatile approach for engineering SARS-CoV-2 variants with high viral recovery efficiency. This new strategy for genomic engineering of SARS-CoV-2 variants was implemented and evaluated for its efficiency in generating point mutations (K417N, L452R, E484K, N501Y, D614G, P681H, P681R, Δ69-70, Δ157-158, E484K+N501Y, and Ins-38F) and multiple mutations (N501Y/D614G and E484K/N501Y/D614G), as well as a large truncation (ΔORF7A) and insertion (GFP). The application of CPEC to mutagenesis also allows the inclusion of a confirmatory step prior to assembly and transfection. This method could be of value in the molecular characterization of emerging SARS-CoV-2 variants as well as the development and testing of vaccines, therapeutic antibodies, and antivirals. IMPORTANCE Since the first emergence of the SARS-CoV-2 variant in late 2020, novel variants have been continuously introduced to the human population, causing severe public health threats. In general, because these variants acquire new genetic mutation/s, it is critical to analyze the biological function of viruses that such mutations can confer. Therefore, we devised a method that can construct SARS-CoV-2 infectious clones and their variants rapidly and efficiently. The method was developed based on a PCR-based circular polymerase extension cloning (CPEC) combined with a specific primer design scheme. The efficiency of the newly designed method was evaluated by generating SARS-CoV-2 variants with single point mutations, multiple point mutations, and a large truncation and insertion. This method could be of value for the molecular characterization of emerging SARS-CoV-2 variants and the development and testing of vaccines and antiviral agents.

Purpose: The commercialization of sleep activity tracking devices has made it possible to manage sleep quality at home. However, it is necessary to verify the reliability and accuracy of wearable devices through comparison with polysomnography (PSG), which is the standard for tracking sleep activity. This study aimed to monitor overall sleep activity using Fitbit Inspire 2™ (FBI2) and to evaluate its performance and effectiveness through PSG under the same conditions., Patients and Methods: We compared the FBI2 and PSG data of nine participants (four male and five female participants; average age, 39 years) without severe sleeping problems. The participants wore FBI2 continuously for 14 days, considering the period of adaptation to the device. FBI2 and PSG sleep data were compared using paired t -tests, Bland-Altman plots, and epoch-by-epoch analysis for 18 samples by pooling data from two replicates., Results: The average values for each sleep stage obtained from FBI2 and PSG showed significant differences in the total sleep time (TST), deep sleep, and rapid eye motion (REM). In the Bland-Altman analysis, TST ( P = 0.02), deep sleep ( P = 0.05), and REM ( P = 0.03) were significantly overstated in FBI2 compared to PSG. In addition, time in bed, sleep efficiency, and wake after sleep onset were overestimated, while light sleep was underestimated. However, these differences were not statistically significant. FBI2 showed a high sensitivity (93.9%) and low specificity (13.1%), with an accuracy of 76%. The sensitivity and specificity of each sleep stage was 54.3% and 62.3%, respectively, for light sleep, 84.8% and 50.1%, respectively, for deep sleep, and 86.4% and 59.1%, respectively for REM sleep., Conclusion: The use of FBI2 as an objective tool for measuring sleep in daily life can be considered appropriate. However, further research is warranted on its application in participants with sleep-wake problems., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Lim et al.)

Owing to the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the capacity of testing systems based on the gold standard real-time reverse transcription-polymerase chain reaction (rRT-PCR) is limited. Rapid antigen tests (RATs) can substantially contribute to the prevention of community transmission, but their further assessment is required. Here, using 1503 nasopharyngeal swabs, we compared the diagnostic performance of four RAT kits (Abbott Panbio™ COVID-19 Ag Rapid Test, SD Biosensor Standard™ Q COVID-19 Ag Test, Humasis COVID-19 Ag Test, and SG Medical Acrosis COVID-19 Ag Test) to the cycle threshold (Ct) values obtained from rRT-PCR. The precision values, area under the curve values, SARS-CoV-2 variant detection ability, and non-SARS-CoV-2 specificity of all four kits were similar. An assay using the Acrosis kit had a significantly better positive detection rate with a higher recall value and cut-off value than that using the other three RAT kits. During the current COVID-19 pandemic, the Acrosis kit is an effective tool to prevent the spread of SARS-CoV-2 in communities.

Enteroviruses (EVs) have been associated with several human diseases. Due to their continuous emergence and divergence, EV species have generated more than 100 types and recombinant strains, increasing the public health threat caused by them. Hence, an efficient and universal cloning system for reverse genetics (RG) of highly divergent viruses is needed to understand the molecular mechanisms of viral pathology and evolution. In this study, we generated a versatile human EV whole-genome cDNA template by enhancing the template-switching method and designing universal primers capable of simultaneous cloning and rapid amplification of cDNA ends (RACE)-PCR of EVs. Moreover, by devising strategies to overcome limitations of previous cloning methods, we simplified significant cloning steps to be completed within a day. Of note, we successfully verified our efficient universal cloning system enabling RG of a broad range of human EVs, including EV-A (EV-A71), EV-B (CV-B5, ECHO6, and ECHO30), EV-C (CV-A24), and EV-D (EV-D68), with viral titers and phenotypes comparable to those of their wild types. This rapid and straightforward universal EV cloning strategy will help us elucidate molecular characteristics, pathogenesis, and applications of a broad range of EV serotypes for further development of genetic vaccines and delivery tools using various replication systems. IMPORTANCE Due to the broad spread, incidence, and genetic divergence of enteroviruses (EVs), it has been challenging to deal with this virus that causes severe human diseases, including aseptic meningitis, myocarditis, encephalitis, and poliomyelitis. Therefore, an efficient and universal cloning system for the reverse genetics of highly divergent EVs contributes to an understanding of the viral pathology and molecular mechanisms of evolution. We have simplified the important cloning steps, hereby enhancing the template-switching method and designing universal primers, which enable the important cloning steps to be completed in a day. We have also successfully demonstrated recovery of a broad range of human EVs, including EV-A to -D types, using this advanced universal cloning system. This rapid and robust universal EV cloning strategy will aid in elucidating the molecular characteristics, pathogenesis, and applications of a wide range of EVs for further development of genetic vaccines and antiviral screening using various replication systems.

Background: Polypharmacy among older people represents a global challenge due to its association with adverse drug events. The reported prevalence of polypharmacy varies widely across countries, and is particularly high in Asian countries. However, there is no multinational study using standardised measurements exploring variations in prescribing trends., Objective: To compare polypharmacy trends in older people in Asia, Australia and the United Kingdom., Design: Multinational, retrospective, time-trend, observational study using a common study protocol., Setting: Outpatient and community settings., Subjects: All individuals aged ≥ 65 years between 2013 and 2016., Methods: We defined polypharmacy as the concomitant use of ≥5 medications for ≥45 days per year. We estimated the annual prevalence of polypharmacy and calculated average annual percentage change (AAPC) to assess the time trends., Results: A total of 1.62 million individuals were included in this study. The highest prevalence of polypharmacy was observed in Hong Kong (46.4%), followed by Taiwan (38.8%), South Korea (32.0%), the United Kingdom (23.5%) and Australia (20.1%) in 2016. For the time trend, the Asian region showed a steady increase, particularly in Hong Kong and South Korea (AAPC: Hong Kong, 2.7%; South Korea, 1.8%; Taiwan, 1.0%). However, Australia and the United Kingdom showed a decreasing trend (Australia, -4.9%; the United Kingdom, -1.1%)., Conclusions: Polypharmacy prevalence in older people was higher in Hong Kong, Taiwan and South Korea, with an increasing trend over time, compared with Australia and the United Kingdom. Our findings underline the necessity to monitor polypharmacy among older people in Asia by conducting government-level interventions and introducing medicine-optimisation strategies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Recurrent spillovers of α- and β-coronaviruses (CoV) such as severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome-CoV, SARS-CoV-2, and possibly human CoV have caused serious morbidity and mortality worldwide. In this study, six receptor-binding domains (RBDs) derived from α- and β-CoV that are considered to have originated from animals and cross-infected humans were linked to a heterotrimeric scaffold, proliferating cell nuclear antigen (PCNA) subunits, PCNA1, PCNA2, and PCNA3. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens, like jewels in a crown. Prime-boost immunizations with 6RBD-np in mice induced significantly high Ab titers against RBD antigens derived from α- and β-CoV and increased interferon (IFN-γ) production, with full protection against the SARS-CoV-2 wild type and Delta challenges. The mosaic 6RBD-np has the potential to induce intergenus cross-reactivity and to be developed as a pan-CoV vaccine against future CoV spillovers.

Memory is inherently context-dependent: internal and environmental cues become bound to learnt information, and the later absence of these cues can impair recall. Here, we developed an approach to leverage context-dependence to optimise learning of challenging, interference-prone material. While navigating through desktop virtual reality (VR) contexts, participants learnt 80 foreign words in two phonetically similar languages. Those participants who learnt each language in its own unique context showed reduced interference and improved one-week retention (92%), relative to those who learnt the languages in the same context (76%)-however, this advantage was only apparent if participants subjectively experienced VR-based contexts as "real" environments. A follow-up fMRI experiment confirmed that reinstatement of brain activity patterns associated with the original encoding context during word retrieval was associated with improved recall performance. These findings establish that context-dependence can be harnessed with VR to optimise learning and showcase the important role of mental context reinstatement., (© 2022. The Author(s).)

Novel highly pathogenic avian influenza (HPAI) H5Nx viruses are predominantly circulating worldwide, with an increasing potential threat of an outbreak in humans. It remains largely unknown how the stably maintained HPAI H5N1 suddenly altered its neuraminidase (NA) to other NA subtypes, which resulted in the emergence and evolution of H5Nx viruses. Here, we found that a combination of four specific amino acid (AA) substitutions (S123P-T156A-D183N- S223 R) in the hemagglutinin (HA) protein consistently observed in the H5Nx markedly altered the NA preference of H5N1 viruses. These molecular changes in H5N1 impaired its fitness, particularly viral growth and the functional activities of the HA and NA proteins. Among the AA substitutions identified, the T156A substitution, which contributed to the NA shift, also dramatically altered the antigenicity of H5N1 viruses, suggesting an occurrence of antigenic drift triggered by selective pressure. Our study shows the importance of how HA and NA complement each other and that antigenic drift in HA can potentially cause a shift in the NA protein in influenza A virus evolution.

As the SARS-CoV-2 pandemic remains uncontrolled owing to the continuous emergence of variants of concern, there is an immediate need to implement the most effective antiviral treatment strategies, especially for risk groups. Here, we evaluated the therapeutic potency of nirmatrelvir, remdesivir and molnupiravir, and their combinations in SARS-CoV-2 infected K18-hACE2 transgenic mice. Systemic treatment of mice with each drug (20 mg/kg) resulted in slightly enhanced antiviral efficacy and yielded an increased life expectancy of only about 20-40% survival. However, combination therapy with nirmatrelvir (20 mg/kg) and molnupiravir (20 mg/kg) in lethally infected mice showed profound inhibition of SARS-CoV-2 replication in both the lung and brain and synergistically improved survival rates up to 80% compared to those with nirmatrelvir (36%, P < 0.001) and molnupiravir (43%, P < 0.001) administered alone. This combination therapy effectively reduced clinical severity score, virus-induced tissue damage, and viral distribution compared to those in animals treated with these monotherapies. Furthermore, all these assessments associated with this combination were also significantly higher than that of mice receiving remdesivir monotherapy (P < 0.001) and the nirmatrelvir (20 mg/kg) and remdesivir (20 mg/kg) combination (P < 0.001), underscored the clinical significance of this combination. By contrast, the nirmatrelvir and remdesivir combination showed less antiviral efficacy, with lower survival compared to nirmatrelvir monotherapy due to the insufficient plasma exposure of the remdesivir, demonstrating the inefficient therapeutic effect of this combination in the mouse model. The combination therapy with nirmatrelvir and molnupiravir contributes to alleviated morbidity and mortality, which can serve as a basis for the design of clinical studies of this combination in the treatment of COVID-19 patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Smoking negatively impacts public health. There are several treatments to quit smoking, and nicotine replacement treatment (NRT) reportedly doubles the smoking cessation rate, with some limitations. Acupuncture is an alternative option with proven effects on smoking cessation. However, there has been no definite report that indicates the efficacy and safety of auricular acupuncture (AA) combined with NRT on smoking cessation., Methods: This is a randomized, assessor-blind, and pragmatic pilot study. We will recruit 40 participants who want to stop smoking and randomly allocate them into an NRT group and an NRT + AA group with a 1:1 ratio. Participants will receive NRT for 4 weeks and the NRT + AA group will receive additional AA treatment with 5 AA points (Shenmen (TF4), lung (CO14), throat (TF3), inner nose (TG4), and endocrine (CO18)) twice a week for 4 weeks. Follow-up will be conducted 1 and 3 months after intervention completion. The primary outcome will be tobacco consumption and abstinence rate determined by calculating the rate of change in cigarette use and a urine test. Secondary outcomes will be the quality of life (EuroQol-5D and visual analogue scale), nicotine dependence (Fagerstrom test for nicotine dependence), nicotine withdrawal (Minnesota nicotine withdrawal scale), physical effects, satisfaction, and safety measurement (adverse events)., Results: We will investigate the efficacy and safety of AA combined with NRT treatment for smoking cessation., Conclusion: Our study will provide additional clinical evidence for AA as an adjuvant treatment for smoking cessation., Trial Registration Number: Clinical Research Information Service (registration number: KCT0007212)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: While much attention has focused on immeasurable time bias as a potential exposure misclassification bias, it may also result in potential selection bias in cohort studies using an as-treated (or per protocol) exposure definition in which patients are censored upon treatment discontinuation., Methods: We examined analytical approaches to minimise informative censoring due to the absence of in-hospital drug data using a case study of β-blocker use and mortality in heart failure. We conducted a cohort study using Korea's healthcare database, including inpatient and outpatient drug data. Using an as-treated exposure definition, patients were followed up until death, β-blocker discontinuation (in the exposed), β-blocker initiation (in the unexposed), or end of study period. In 'complete prescription' analysis using inpatient and outpatient drug data, we estimated hazard ratios (HR) and 95% confidence intervals (CI) using a Cox proportional hazard model. In outpatient drug-based analyses, we attempted to reduce the bias using stabilised inverse probability weighting (IPW) for treatment crossovers, hospitalisation, and all artificial censorings., Results: An HR of 0.89 (95% CI 0.74-1.07) for β-blocker use versus non-use for all-cause mortality was found in 'complete prescription' analysis. Benefits were exaggerated when follow-up was assessed using outpatient drug data only (HR 0.71; 95% CI 0.57-0.89). Weighting by stabilised IPW for treatment crossovers and hospitalisation reduced the bias., Conclusions: When using an as-treated exposure definition, missing in-hospital drug data induced selection bias in our case study. Using IPW for censoring mitigated bias from the hospitalisation-induced censorings., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third highly pathogenic human coronavirus and is rapidly transmitted by infected individuals regardless of their symptoms. During the COVID-19 pandemic, owing to the dearth of skilled healthcare workers (HCWs) to collect samples for early diagnosis, self-collection emerged as a viable alternative. To evaluate the reliability of self-collection, we compared the virus detection rate using 3990 self-collected swabs and HCW-collected swabs, procured from the same individuals and collected immediately after the self-collection. The results of multiplex reverse-transcription quantitative polymerase chain reaction revealed that the viral load in the HCW-collected swabs was marginally (18.4-28.8 times) higher than that in self-collected swabs. Self-collection showed no significant difference in sensitivity and specificity from HCW-collection (κ = 0.87, McNemar's test; p = 0.19), indicating a comparable performance. These findings suggest that self-collected swabs are acceptable substitutes for HCW-collected swabs, and that their use improved the specimen screening efficiency and reduced the risk of SARS-CoV-2 infection among HCWs during and after the COVID-19 pandemic., Competing Interests: The authors declare no conflicts of interest.

Severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is still rapidly spreading as of March 2022. An accurate and rapid molecular diagnosis is essential to determine the exact number of confirmed cases. Currently, the viral transport medium (VTM) required for testing is in short supply due to a sharp increase in the laboratory tests performed, and alternative VTMs are needed to alleviate the shortage. Guanidine thiocyanate-based media reportedly inactivate SARS-CoV-2 and are compatible with quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays, but the compatibility and the viral detection capacity have not been fully validated. To evaluate the guanidine thiocyanate-based Gene Transport Medium (GeneTM) as an alternative VTM, we prepared 39 SARS-CoV-2-positive and 7 SARS-CoV-2-negative samples in GeneTM, eNAT™, and phosphate-buffered saline (PBS). The cycle threshold (Ct) values of three SARS-CoV-2 targets (the S, RdRP, and N genes) were analyzed using RT-qPCR testing. The comparison of Ct values from the positive samples showed a high correlation ( R 2 = 0.95-0.96) between GeneTM and eNAT™, indicating a comparable viral detection capacity. The delta Ct values of the SARS-CoV-2 genes in each transport medium were maintained for 14 days at cold (4°C) or room (25°C) temperatures, suggesting viral samples were stably preserved in the transport media for 14 days. Together, GeneTM is a potential alternative VTM with comparable RT-qPCR performance and stability to those of standard media., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Young Hyun Baek et al.)

Rapid diagnosis is essential for the control and prevention of H5 highly pathogenic avian influenza viruses (HPAIVs). However, highly sensitive and rapid diagnostic systems have shown limited performance due to specific antibody scarcity. In this study, two novel specific monoclonal antibodies (mAbs) for clade 2.3.4.4 H5Nx viruses were developed by using an immunogen from a reversed genetic influenza virus (RGV). These mAbs were combined with fluorescence europium nanoparticles and an optimized lysis buffer, which were further used for developing a fluorescent immunochromatographic rapid strip test (FICT) for early detection of H5Nx influenza viruses on chicken stool samples. The result indicates that the limit of detection (LoD) of the developed FICT was 40 HAU/mL for detection of HPAIV H5 clade 2.3.4.4b in spiked chicken stool samples, which corresponded to 4.78 × 10 4 RNA copies as obtained from real-time polymerase chain reaction (RT-PCR). An experimental challenge of chicken with H5N6 HPAIV is lethal for chicken three days post-infection (DPI). Interestingly, our FICT could detect H5N6 in stool samples at 2 DPI earlier, with 100% relative sensitivity in comparison with RT-PCR, and it showed 50% higher sensitivity than the traditional colloidal gold-based rapid diagnostic test using the same mAbs pair. In conclusion, our rapid diagnostic method can be utilized for the early detection of H5Nx 2.3.4.4 HPAIVs in avian fecal samples from poultry farms or for influenza surveillance in wild migratory birds.

Minoxidil is the most widely used treatment for hair growth, but has been associated with several side effects. In this study, we investigated the effects of heat-killed Enterococcus faecalis EF-2001 on hair loss prevention and regrowth using human dermal papilla cells and male C57BL/6 mice. To examine the effects of EF-2001, we used minoxidil as the positive control. In the in vitro experiments, EF-2001 treatment (75-500 μg/mL) led to the proliferation of human dermal papilla cells in a concentration-dependent manner. In the in vivo experiment, the topical application of 200 µL EF-2001 on the dorsal surface of C57BL/6 male mice led to hair growth. Changes in hair regrowth were examined by visual comparison and hematoxylin and eosin staining of skin sections. We also determined the expression levels of marker genes ( Wnt ) and growth factors (fibroblast growth factor, insulin growth factor 1, and vascular endothelial growth factor) in the skin tissues of the back of each mouse using a quantitative polymerase chain reaction. EF-2001 accelerated the progression of hair regrowth in mice and promoted hair-follicle conversion from telogen to anagen, likely by increasing the expression levels of growth factors and marker genes.

Background: The efficacy of bone-targeting agents has been confirmed, but the generalizability of results to Asia is in question., Objective: We aimed to evaluate and compare treatment persistence and re-initiation with different bone-targeting agents among patients with bone metastases from solid tumors., Methods: This population-based cohort study included patients with bone metastasis with breast, lung, or prostate cancer who initiated bone-targeting agents, including denosumab, zoledronic acid, and pamidronate in Taiwan (2013-17), Hong Kong (2013-17), and Korea (2012-16). We described the patients' persistence with bone-targeting agents, by evaluating the interruption probability, and compared risks of treatment interruption. The rates of re-initiation with index bone-targeting agents were evaluated., Results: We included 5127 patients (denosumab: 3440, zoledronic acid: 1210, pamidronate: 477) from Taiwan, 883 patients (denosumab: 458, zoledronic acid: 357, pamidronate: 68) from Hong Kong, and 4800 patients (zoledronic acid: 4068, pamidronate: 732) from Korea. Compared with zoledronic acid, denosumab had a lower risk of interruption in Taiwan (adjusted hazard ratio: 0.44; 95% confidence interval 0.40-0.48) and Hong Kong (0.36; 0.28-0.45). However, pamidronate was more likely to be interrupted than zoledronic acid in Taiwan (1.31; 1.11-1.54) and Korea (2.06; 1.83-2.32), but not in Hong Kong (1.13; 0.71-1.78). After discontinuation, original treatments with denosumab in Taiwan and zoledronic acid in Hong Kong were more likely to be resumed, while in Korea, the rates were similar among the bisphosphonates., Conclusions: Denosumab was associated with a lower risk of interruption than bisphosphonates in patients with bone metastases in Taiwan and Hong Kong. Further investigations may be required to verify patients' actual reasons for discontinuation., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Recent evidence suggests that gut microbiota dysbiosis adversely affects the efficacy of immune checkpoint inhibitors (ICIs). Our objective was to investigate the association between concomitant use of proton pump inhibitors (PPIs) and ICIs, and poor prognosis in patients with nonsmall cell lung cancer (NSCLC). We conducted a cohort study using a completely enumerated lung cancer cohort from a nationwide healthcare database in South Korea. We identified 2963 patients treated with ICIs as second-line or later therapy for stage ≥IIIB NSCLC. PPI use was ascertained within 30-days before and on the date of ICI initiation, and nonuse was defined as no prescription of PPIs during this period. Using national vital statistics in South Korea, we assessed the risk of all-cause mortality associated with concomitant PPI use through a propensity score-matched Cox proportional hazard model. Among 1646 patients included after 1:1 propensity score-matching, concomitant PPI use was associated with a 28% increased risk of all-cause mortality, compared to nonuse (adjusted hazard ratio [HR] 1.28; 95% confidence intervals [CIs], 1.13-1.46). We observed an increased risk when we restricted the analysis to new users of PPI (adjusted HR = 1.64; 95% CI = 1.25-2.17). Subgroup analysis showed that PPI use was associated with high mortality risk among patients with viral hepatitis (adjusted HR = 2.72; 95% CI = 1.54-4.78; P interaction  = .048). Our study indicates that PPI use is associated with poor prognosis in NSCLC patients treated with ICIs. Further prospective studies are required to determine the risk-benefit balance of concomitant use of PPIs and ICIs., (© 2021 UICC.)

Background: Rheumatoid arthritis (RA) is a common chronic autoimmune disease that contributes to progressive disability, systemic complications, higher mortality, and societal burden. Typical symptoms of RA include symmetrical pain and swelling in multiple joints, morning stiffness, and elevated levels of erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor. The representative treatment for RA is medication, including disease-modifying antirheumatic drugs, glucocorticoids, and nonsteroidal anti-inflammatory drugs. However, these medications are not yet curative nor preventative and are associated with several adverse effects, leading to their discontinuation. Recent articles reported that Simiao Xiaobi decoction (SXD) could relieve the symptoms of RA by clinical trial and experimental study, but an evidence-based review on the effectiveness and safety of SXD on RA has not yet been provided., Methods: Searching for randomized controlled trials on the use of SXD for RA will be performed by using multiple electronic databases, manual search, and contacting the authors by e-mail if needed. Studies will be selected according to the predefined criteria and the data collected on study participants, interventions, control groups, outcome measurements, their results, adverse events, and risk of bias will be summarized. The primary outcome will be the disease activity score (including effective rate, swollen joint count, tender joint count, and morning stiffness), and the secondary outcomes will be blood tests (including erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor) and adverse events. We will use Review Manager software to perform a meta-analysis, the Cochrane Collaboration "risk of bias" tool for assessing the risk of bias, and grades of recommendation, assessment, development and evaluation for the determination of the quality of evidence., Trial Registration Number: https://inplasy.com; INPLASY202230026., Results: We are going to investigate the effectiveness and safety of SXD for RA., Conclusion: This study will provide reliable evidence on whether SXD is effective on RA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Rheumatoid arthritis (RA) is the common autoimmune disease with low quality of life. The representative treatment is medication and medication usage has improved through update of clinical guidelines, however, there are still limitations. Bee venom (BV) has been reported to have meaningful therapeutic effects and the possibility of alternative options for RA through several types of studies, but there is no well-organised and recent published systematic review (SR)., Methods: We will search randomised controlled trials about the BV on RA from the inception to 31 May 2022 in various databases, manual research and contacting authors. Electronic databases will include MEDLINE, EMBASE, Cochrane library, China National Knowledge Infrastructure, CiNii, J-STAGE, KoreaMed, Korean Medical Database, Korean Studies Information Service System, National Digital Science Library, Korea Institute of Science and Technology Information and Oriental Medicine Advanced Searching Integrated System. With screening and reviewing process, we will identify the eligible studies and extract the needed data. The primary outcome will be the disease activity scores indicating the improvement of RA symptoms (American College of Rheumatology response criteria 20, 50, 70), functions (Health Assessment Questionnaire, Disease Activity Score of 28 joints), joint (Western Ontario and McMaster universities osteoarthritis index), pain (Visual Analogue Scale, Numerical Rating Scale) and effective rate. The secondary outcomes will be the RA-related blood test levels and adverse events. We will perform a meta-analysis by Review Manager software, the assessment of risk of bias by Cochrane Collaboration 'risk of bias' and the determination of quality of evidence by Grades of Recommendation, Assessment, Development and Evaluation., Ethics and Dissemination: Our SR will suggest the clinical evidence of the use of BV for RA to patient, clinicians and policymakers. We will publish our results in a peer-review journal., Prospero Registration Number: CRD42021238058., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: and purpose: Although several studies have reported that thread embedding acupuncture (TEA) is effective for lumbar herniated intervertebral disc (LHIVD), the evidence remains limited because previous studies had a high risk of bias. This study aimed to investigate the efficacy and safety of TEA for LHIVD through a rigorously designed trial., Materials and Methods: This was a randomized, patient-assessor-blinded, sham-controlled trial. Participants were screened according to eligibility criteria, and 70 patients with LHIVD were randomly allocated to the TEA and sham TEA (STEA) groups in a 1:1 ratio. Both groups received TEA or STEA treatment at 23 acupoints once per week for eight weeks. Changes in low back pain, radiating pain, Oswestry disability index, Roland-Morris disability questionnaire, EuroQol 5-Dimensions 5-Levels, and global perceived effect were measured at baseline and at 4, 8, 12, and 16 weeks after screening and compared between the two groups., Results: TEA showed no significant difference in all outcomes compared to STEA immediately after eight weeks of treatment. After an additional eight weeks of follow-up, TEA showed a more significant effect on the low back pain than STEA (p < 0.05) and showed a better tendency in maintaining or enhancing the improvement of radiating pain, function, and quality of life even after the end of treatment. No serious adverse events were observed., Conclusion: TEA is effective in improving low back pain in patients with LHIVD and may help improve function and quality of life, especially in the long term., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A significant number of individuals suffer from low back pain throughout their lifetime, and the medical costs related to low back pain and disc herniation are gradually increasing in Korea. Korean medicine interventions have been used for the treatment of lumbar intervertebral disc herniation. Therefore, we aimed to update the existing Korean medicine clinical practice guidelines for lumbar intervertebral disc herniation. A review of the existing guidelines for clinical treatment and analysis of questionnaires targeting Korean medicine doctors were performed. Subsequently, key questions on the treatment method of Korean medicine used for disc herniation in actual clinical trials were derived, and drafts of recommendations were formed after literature searches using the Grading of Recommendations, Assessment, Development and Evaluation. An expert consensus was reached on the draft through the Delphi method and final recommendations were made through review by the development project team and the monitoring committee. Fifteen recommendations for seven interventions for lumbar disc herniation were derived, along with the grade of recommendation and the level of evidence. The existing Korean medicine clinical practice guidelines for lumbar intervertebral disc herniation have been updated. Continuous updates will be needed through additional research in the future.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly contagious and causes coronavirus disease 2019 (COVID-19). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) is the most accurate and reliable molecular assay to detect active SARS-CoV-2 infection. However, a rapid increase in test subjects has created a global bottleneck in testing capacity. Given that efficient nucleic acid extraction greatly affects reliable and accurate testing results, we compared three extraction platforms: MagNA Pure 96 DNA and Viral NA Small Volume kit on MagNA Pure 96 (Roche, Basel, Switzerland), careGENE TM Viral/Pathogen HiFi Nucleic Acid Isolation kit (WELLS BIO Inc., Seoul, Korea) on KingFisher Flex (Thermo Fisher Scientific, Rocklin, CA, USA), and SGRespi TM Pure kit (Seegene Inc., Seoul, Korea) on Maelstrom 9600 (Taiwan Advanced Nanotech Inc., Taoyuan, Taiwan). RNA was extracted from 245 residual respiratory specimens from the different types of samples (i.e., NPS, sputum, and saliva) using three different kits. The 95% limits of detection of median tissue culture infectious dose per milliliter (TCID 50 /mL) for the MagNA Pure 96, KingFisher Flex, and Maelstrom 9600 were 0.37-3.15 × 10 1 , 0.41-3.62 × 10 1 , and 0.33-1.98 × 10 1 , respectively. The KingFisher Flex platform exhibited 99.2% sensitivity and 100% specificity, whereas Maelstrom 9600 exhibited 98.3-100% sensitivity and 100% specificity. Bland-Altman analysis revealed a 95.2% concordance between MagNA Pure 96 and KingFisher Flex and 95.4% concordance between MagNA Pure 96 and Maelstrom 9600, indicating that all three platforms provided statistically reliable results. This suggests that two modifying platforms, KingFisher Flex and Maelstrom 9600, are accurate and scalable extraction platforms for large-scale SARS-CoV-2 clinical detection and could help the management of COVID-19 patients.