Adenovirus expressing nc886, an anti-interferon and anti-apoptotic non-coding RNA, is an improved gene delivery vector.

Recombinant adenovirus (rAdV) vector is the most promising vehicle to deliver an exogenous gene into target cells and is preferred for gene therapy. Exogenous gene expression from rAdV is often too inefficient to induce phenotypic changes and the amount of administered rAdV must be very high to achieve a therapeutic dose. However, it is often hampered because a high dose of rAdV is likely to induce cytotoxicity by activating immune responses. nc886, a 102-nucleotide non-coding RNA that is transcribed by RNA polymerase III, acts as an immune suppressor and a facilitator of AdV entry into the nucleus. Therefore, in this study, we have constructed an rAdV expressing nc886 (AdV:nc886) to explore whether AdV:nc886 overcomes the aforementioned drawbacks of conventional rAdV vectors. When infected into mouse cell lines and mice, AdV:nc886 expresses a sufficient amount of nc886, which suppresses the induction of interferon-stimulated genes and apoptotic pathways triggered by AdV infection. As a result, AdV:nc886 is less cytotoxic and produces more rAdV-delivered gene products, compared with the parental rAdV vector lacking nc886. In conclusion, this study demonstrates that the nc886-expressing rAdV could become a superior gene delivery vehicle with greater safety and higher efficiency for in vivo gene therapy.

Delta check limits for thyroid function tests adjusted for clinical settings.

BACKGROUND: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings. METHODS: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets. RESULTS: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets. CONCLUSIONS: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs.

Laboratory Preparation for Digital Medicine in Healthcare 4.0: An Investigation Into the Awareness and Applications of Big Data and Artificial Intelligence.

Background: Healthcare 4.0. refers to the integration of advanced technologies, such as artificial intelligence (AI) and big data analysis, into the healthcare sector. Recognizing the impact of Healthcare 4.0 technologies in laboratory medicine (LM), we seek to assess the overall awareness and implementation of Healthcare 4.0 among members of the Korean Society for Laboratory Medicine (KSLM). Methods: A web-based survey was conducted using an anonymous questionnaire. The survey comprised 36 questions covering demographic information (seven questions), big data (10 questions), and AI (19 questions). Results: In total, 182 (17.9%) of 1,017 KSLM members participated in the survey. Thirty-two percent of respondents considered AI to be the most important technology in LM in the era of Healthcare 4.0, closely followed by 31% who favored big data. Approximately 80% of respondents were familiar with big data but had not conducted research using it, and 71% were willing to participate in future big data research conducted by the KSLM. Respondents viewed AI as the most valuable tool in molecular genetics within various divisions. More than half of the respondents were open to the notion of using AI as assistance rather than a complete replacement for their roles. Conclusions: This survey highlighted KSLM members' awareness of the potential applications and implications of big data and AI. We emphasize the complexity of AI integration in healthcare, citing technical and ethical challenges leading to diverse opinions on its impact on employment and training. This highlights the need for a holistic approach to adopting new technologies.

Quantitative Evaluation of the Real-World Harmonization Status of Laboratory Test Items Using External Quality Assessment Data.

Background: In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory results in applications, such as machine learning through big data, understanding the level of harmonization for each test would be beneficial. We aimed to develop a quantitative harmonization index that reflects the harmonization status of real-world laboratory tests. Methods: We collected 2021-2022 external quality assessment (EQA) results for eight tests (HbA1c, creatinine, total cholesterol, HDL-cholesterol, triglyceride, alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and prostate-specific antigen [PSA]). This EQA was conducted by the Korean Association of External Quality Assessment Service, using commutable materials. The total analytical error of each test was determined according to the bias% and CV% within peer groups. The values were divided by the total allowable error from biological variation (minimum, desirable, and optimal) to establish a real-world harmonization index (RWHI) at each level (minimum, desirable, and optimal). Good harmonization was arbitrarily defined as an RWHI value ≤ 1 for the three levels. Results: Total cholesterol, triglyceride, and CEA had an optimal RWHI of ≤ 1, indicating an optimal harmonization level. Tests with a desirable harmonization level included HDL-cholesterol, AFP, and PSA. Creatinine had a minimum harmonization level, and HbA1c did not reach the minimum harmonization level. Conclusions: We developed a quantitative RWHI using regional EQA data. This index may help reflect the actual harmonization level of laboratory tests in the field.

Frequency of Fabry disease in chronic kidney disease patients including patients on renal replacement therapy in Korea.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase (α-Gal A), affecting multiple organs including kidney. In this study, we aimed to determine the prevalence of FD in patients with chronic kidney disease (CKD) including those on renal replacement therapy in Korea. METHODS: This is a national, multicenter, observational study performed between August 24, 2017 and February 28, 2020. Patients with the presence of proteinuria or treated on dialysis were screened by measuring the α-Gal A enzyme activity using either dried blood spot or whole blood, and plasma globotriaosylsphingosine (lyso-GL3) concentration. A GLA gene analysis was performed in patients with low α-Gal A enzyme activity or increased plasma lyso-GL3 concentration. RESULTS: Of 897 screened patients, 405 (45.2%) were male and 279 (31.1%) were on dialysis. The α-Gal A enzyme activity was measured in 891 patients (99.3%), and plasma lyso-GL3 concentration was measured in all patients. Ten patients were eligible for a GLA gene analysis: eight with low α-Gal A enzyme activity and two with increased plasma lyso-GL3 concentration. The GLA mutations were analyzed in nine patients and one patient was found with a pathogenic mutation. Therefore, one patient was identified with FD, giving a prevalence of 0.1% (1 of 897) in this CKD population. CONCLUSION: Although the prevalence of FD in the CKD population was low (0.1%), screening tests are crucial to detect potential diseases in patients with relatives who can benefit from early treatment.

HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape.

H3.3, the most common replacement variant for histone H3, has emerged as an important player in chromatin dynamics for controlling gene expression and genome integrity. While replicative variants H3.1 and H3.2 are primarily incorporated into nucleosomes during DNA synthesis, H3.3 is under the control of H3.3-specific histone chaperones for spatiotemporal incorporation throughout the cell cycle. Over the years, there has been progress in understanding the mechanisms by which H3.3 affects domain structure and function. Furthermore, H3.3 distribution and relative abundance profoundly impact cellular identity and plasticity during normal development and pathogenesis. Recurrent mutations in H3.3 and its chaperones have been identified in neoplastic transformation and developmental disorders, providing new insights into chromatin biology and disease. Here, we review recent findings emphasizing how two distinct histone chaperones, HIRA and DAXX, take part in the spatial and temporal distribution of H3.3 in different chromatin domains and ultimately achieve dynamic control of chromatin organization and function. Elucidating the H3.3 deposition pathways from the available histone pool will open new avenues for understanding the mechanisms by which H3.3 epigenetically regulates gene expression and its impact on cellular integrity and pathogenesis.

Impact of Academia-Government Collaboration on Laboratory Medicine Standardization in South Korea: analysis of eight years creatinine proficiency testing experience.

OBJECTIVES: To evaluate the performance of the Academia-Government Collaboration for Laboratory Medicine Standardization in Korea (KR-STDZN) based on data from KR-STDZN proficiency testing (KR-STDZN-PT) for creatinine over eight years (2015-2022). METHODS: We used KR-STDZN-PT data of creatinine tests from 2015 to 2022. Acceptance of the participating institutions' test results was assessed by calculating the acceptance performance as absolute bias (absBias%), total coefficient of variance (tCV%), and total error (TE%) for each sample using six measurements from each institution and true values of each reference material. The test result was considered acceptable when absBias%, tCV%, and TE% were <5.10, <3.20, and <11.40 %, respectively. The proportion of acceptable institutions among all participating institutions in each round was defined as the acceptance rate. Improvements in absBias%, tCV%, and TE% were analyzed using creatinine concentration ranges in samples. RESULTS: The number of participating institutions increased from 2015 to 2017 but remained consistent since 2018. The acceptance rates for absBias% and TE% increased from 52.2 and 77.6 %, in 2015 and to 90.7 and 96.3 %, in 2022, respectively. The acceptance rate for tCV% remained in the 90 % range for eight years. When creatinine <3 mg/dL, mean absBias%, and mean TE% improved significantly in 2021-2022 compared to 2015-2016 (p<0.05). When creatinine >3 mg/dL, acceptance performance did not improve. Mean tCV% remained consistent annually regardless of creatinine concentration. No significant variations in test methods were observed. CONCLUSIONS: The collaboration between academia and the government improved creatinine testing quality. Nevertheless, KR-STDZN must be expanded and refined.

Performance Evaluation of the Roche Cobas 5800 HBV and HCV Tests: Comparison of the 200 and 500 µL Protocols.

Background: Clinical management of patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) relies on the viral load (VL). The Cobas 5800 system (Roche Diagnostics) can determine VLs in 200 and 500 µL samples, but the performance of each protocol has not been compared. We evaluated the performance of both protocols for the HBV and HCV tests. Methods: Precision and linearity were verified using commercial panels. Probit analyses were used to determine limits of detection (LoDs). The results obtained with 336 samples were compared using the 200 and 500 µL protocols. Data from 6,737 retrospective HBV and 768 HCV samples were compared to estimate the effects of the different LoDs on the diagnostic results of the protocols. Correlations between protocols were tested with Spearman's rank correlation coefficients (rho). Results: The precision and linearity of both protocols were verified. The LoDs for the 200 and 500 µL protocols were 6.5 and 2.7 IU/mL for HBV and 29.7 and 8.2 IU/mL for HCV, respectively. The agreement between the protocols ranged from 0.8 to 1.0. The results obtained with the HBV and HCV tests showed a strong correlation (rho=0.994). Only 0.4% of HBV and 0.4% of HCV test results were affected by the LoDs of the 200 µL protocol. Conclusions: The Cobas 5800 200 and 500 µL protocols for the HBV DNA and HCV RNA tests demonstrated excellent performance. These findings establish the 200 µL protocol as a new option for low-volume samples, especially for pediatric and difficult-to-bleed patients.

Target blood pressure in Korean hemodialysis patients for optimal survival.

Background: Hypertension is a major cardiovascular risk factor in hemodialysis patients. This study identified the optimal blood pressure (BP) target for Korean hemodialysis patients using the Korean Renal Dialysis System (KORDS) dataset from the Korean Society of Nephrology and a pooled analysis for previous studies. Methods: Hemodialysis patients were classified according to their systolic (SBP) and diastolic BP (DBP) at intervals of 20 and 10 mmHg, respectively. As a primary and secondary outcome, all-cause mortality and cardiovascular mortality were evaluated. Subsequently, pooled analysis with previous literatures was performed. Results: Among 70,607 patients, 13,708 (19.4%) died in 2,426 days (interquartile range, 1,256-4,075 days). Mean SBP and DBP were 143.0 ± 19.6 and 78.5 ± 12.0 mmHg. In multivariable Cox regression, the patients with SBP of <120 and ≥180 mmHg showed 1.10- and 1.12-times increased risk of all-cause mortality compared to SBP of 120-140 mmHg. Meanwhile, DBP showed no significant association. In subgroup analysis, patients aged <70 years and without diabetes had a U-shaped SBP-mortality association. Cardiovascular mortality was increased in SBP of ≥160 mmHg compared to 120-140 mmHg, but it was not in <120 mmHg. Pooled analysis with previous studies mostly showed elevated risk in SBP of <120 mmHg, but the risks in 140-160 and 160-180 mmHg were not consistent. Conclusion: Extremely lowering BP (<120 mmHg) or uncontrolled hypertension (≥160 mmHg) should be avoided to optimize survival in Korean hemodialysis patients. Detailed analysis for patients with SBP of 120-160 mmHg should be studied further under uniform BP measurement, along with consideration of risk of intradialytic hypotension. Tailored recommendations regarding patient risk factors also should be considered.

Cardiovascular Collapse after the Induction of Anesthesia Due to the MASS Effect of Unruptured Giant Bullae.

Background and Objectives: Giant bullae rupture easily and cause tension pneumothorax, which can cause problems during general anesthesia. However, the hemodynamic instability that can occur due to the mass effect of an unruptured giant bulla should not be overlooked. Case report: A 43-year-old male patient visited the emergency room with an abdominal wound. There was a giant emphysematous bulla in the left lung. Emergency surgery was decided upon because there was active bleeding according to abdominal CT. After tracheal intubation, the patient's blood pressure and pulse rate dramatically decreased. His blood pressure did not recover despite the use of vasopressors and discontinuation of positive pressure ventilation applied to the lungs. Thus, a bullectomy was immediately performed. The patient's blood pressure and pulse rate were normalized after the bullectomy. Conclusions: If emergency surgery under general anesthesia is required in a patient with a giant emphysematous bulla, it is safe to minimize positive pressure ventilation and remove the giant emphysematous bulla as soon as possible before proceeding with the remainder of the surgery. Tension pneumothorax due to the rupturing of a bulla should be considered first. However, hemodynamic changes might occur due to the mass effect caused by a giant bulla.

Cross-Activation of Regulatory T Cells by Self Antigens Limits Self-Reactive and Activated CD8+ T Cell Responses.

The interaction between regulatory T (Treg) cells and self-reactive T cells is a crucial mechanism for maintaining immune tolerance. In this study, we investigated the cross-activation of Treg cells by self-antigens and its impact on self-reactive CD8+ T cell responses, with a focus on the P53 signaling pathway. We discovered that major histocompatibility complex (MHC) I-restricted self-peptides not only activated CD8+ T cells but also induced the delayed proliferation of Treg cells. Following HLA-A*0201-restricted Melan-A-specific (pMelan) CD8+ T cells, we observed the direct expansion of Treg cells and concurrent suppression of pMelan+CD8+ T cell proliferation upon stimulation with Melan-A peptide. Transcriptome analysis revealed no significant alterations in specific signaling pathways in pMelan+CD8+ T cells that were co-cultured with activated Treg cells. However, there was a noticeable upregulation of genes involved in P53 accumulation, a critical regulator of cell survival and apoptosis. Consistent with such observation, the blockade of P53 induced a continuous proliferation of pMelan+CD8+ T cells. The concurrent stimulation of Treg cells through self-reactive TCRs by self-antigens provides insights into the immune system's ability to control activated self-reactive CD8+ T cells as part of peripheral tolerance, highlighting the intricate interplay between Treg cells and CD8+ T cells and implicating therapeutic interventions in autoimmune diseases and cancer immunotherapy.

Variant Analysis of the Thymidine Kinase and DNA Polymerase Genes of Herpes Simplex Virus in Korea: Frequency of Acyclovir Resistance Mutations.

The thymidine kinase (TK) and DNA polymerase (pol) genes of the herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are two important genes involved in antiviral resistance. We investigated the genetic polymorphisms of the HSV-TK and pol genes in clinical isolates from Korean HSV-infected patients using next-generation sequencing (NGS) for the first time in Korea. A total of 81 HSV-1 and 47 HSV-2 isolates were examined. NGS was used to amplify and sequence the TK and pol genes. Among the 81 HSV-1 isolates, 12 and 17 natural polymorphisms and 9 and 23 polymorphisms of unknown significance in TK and pol were found, respectively. Two HSV-1 isolates (2.5%) exhibited the E257K amino acid substitution in TK, associated with antiviral resistance. Out of 47 HSV-2 isolates, 8 natural polymorphisms were identified in TK, and 9 in pol, with 13 polymorphisms of unknown significance in TK and 10 in pol. No known resistance-related mutations were observed in HSV-2. These findings contribute to our understanding of the genetic variants associated with antiviral resistance in HSV-1 and HSV-2 in Korea, with frequencies of known antiviral resistance-related mutations of 2.5% and 0% in HSV-1 and HSV-2, respectively.

A questionnaire survey on the diagnosis and treatment of Fabry nephropathy in clinical practice.

BACKGROUND: Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. METHODS: A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. RESULTS: Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. CONCLUSION: Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

Usefulness and performance evaluation of serum KL-6 and SP-A assays in healthy individuals and patients with interstitial lung disease.

BACKGROUND: Interstitial lung abnormalities (ILAs) are associated with the risk of progression to interstitial lung diseases (ILDs). Krebs von den Lungen 6 (KL-6) and surfactant protein (SP)-A have been used as biomarkers of ILDs. In this study, we evaluated the levels of these biomarkers and identified their clinical correlations in healthy individuals to assess their usefulness in the diagnosis of ILAs. METHODS: The patient samples were categorized into three groups: healthy, disease, and ILD groups. We used the automated immunoassay HISCL KL-6 and SP-A assay kits. The analytical performance evaluation involved precision, linearity, comparison, establishment of reference intervals, and determination of the cutoff points. We also analyzed the correlations between presence of abnormalities on chest radiography and computed tomography (CT) or pulmonary function test (PFT) and serum levels in the healthy group. RESULTS: KL-6 and SP-A assays showed good analytical performance. The KL-6 and SP-A cutoff values were 304 U/mL and 43.5 ng/mL between the ILD and healthy groups, respectively, which were lower than the values recommended by the manufacturer. In the clinical correlations with radiological findings, SP-A values in subjects with lung abnormalities on CT scans were significantly higher than those in normal scans. There was no significant difference in KL-6 and SP-A levels among PFT patterns; however, both serum levels in the mixed pattern showed higher values than those in the other patterns. CONCLUSIONS: The results revealed a positive association between increased serum levels of SP-A and KL-6 and clinical characteristics as incidental findings on chest imaging and reduced lung function.

Impaired NRF2 Inhibits Recovery from Ischemic Reperfusion Injury in the Aging Kidney.

Deteriorating kidney function is frequently observed in the elderly population, as well as vulnerability to acute kidney failure, such as ischemic/reperfusion injury (IRI), and inadequate recovery from IRI is one of the mechanisms of kidney dysfunction in the elderly. The potential mediators in the progression of kidney dysfunction in the aging kidney have not yet been clearly revealed. In this study, we investigated the role of nuclear factor erythroid 2-related factor 2 (NRF2), which is an essential regulator of cellular redox homeostasis, in restoring kidney function after IRI in the aging kidney. NRF2 expression decreased significantly in the kidneys of old mice, as well as histologic and functional renal recovery after IRI; 45-min renal pedicle clamping was retarded in old compared with young mice. Persistent renal injury during the recovery phase after IRI was aggravated in NRF2 knockout (KO) mice compared to wild-type mice. Oxidative stress occurred in NRF2 KO old mice during the IRI recovery phase along with decreased expression of mitochondrial OXPHOS-related proteins and a reduction in mitochondrial ATP content. In vitro, hypoxia/reoxygenation (H/R) injury was aggravated in senescent human proximal tubuloepithelial cells after NRF2 restriction using NRF2 siRNA, which also increased the level of oxidative stress and deteriorated mitochondrial dysfunction. Treating the mice with an NRF2 activator, CDDO-Me, alleviated the injury. These results suggest that NRF2 may be a therapeutic target for the aging kidney.

The Effect of DNA Methylation in the Development and Progression of Chronic Kidney Disease in the General Population: An Epigenome-Wide Association Study Using the Korean Genome and Epidemiology Study Database.

BACKGROUND: Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function and examine whether the identified CpG sites are associated with CKD development. METHOD: We analyzed DNA methylation patterns of 440 participants in the Korean Genome and Epidemiology Study (KoGES) with estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m2 at baseline. CKD development was defined as a decrease in the eGFR of <60 at any time during an 8-year follow-up period ("CKD prediction" analysis). In addition, among the 440 participants, 49 participants who underwent a second methylation profiling were assessed for an association between a decline in kidney function and changes in the degree of methylation of CpG sites during the 8 years ("kidney function slope" analysis). RESULTS: In the CKD prediction analysis, methylation profiles of a total of 403,129 CpG sites were evaluated at baseline in 440 participants, and increased and decreased methylation of 268 and 189 CpG sites, respectively, were significantly correlated with the development of CKD in multivariable logistic regression. During kidney function slope analysis using follow-up methylation profiles of 49 participants, the percent methylation changes in 913 CpG sites showed a linear relationship with the percent change in eGFR during 8 years. During functional enrichment analyses for significant CpG sites found in the CKD prediction and kidney function slope analyses, we found that those CpG sites represented MAPK, PI3K/Akt, and Rap1 pathways. In addition, three CpG sites from three genes, NPHS2, CHCHD4, and AHR, were found to be significant in the CKD prediction analysis and related to a decline in kidney function. CONCLUSION: It is suggested that DNA methylation on specific genes is associated with the development of CKD and the deterioration of kidney function.

Tracking the Genomic Evolution of SARS-CoV-2 for 29 Months in South Korea.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, with the persistent emergence of variants of concern (VOCs). Therefore, this study aimed to track the genomic evolution of SARS-CoV-2 strains by sequencing the spike protein for 29 months, which accounted for the majority of the COVID-19 pandemic period. A total of 109 swabs from patients with confirmed coronavirus disease 2019 (COVID-19) infection were randomly collected between March 2020 and July 2022. After genomic sequencing, we analyzed the naming systems and phylogenetic trees. Five surge peaks of COVID-19 cases have been reported in South Korea, resulting in 14,000,000 cumulative confirmed cases and 17,000 deaths. Among the sequenced samples, 34 wild-type strains and 75 VOCs, including 4 Alpha, 33 Delta, 2 Epsilon, and 36 Omicron VOCs, were identified. Omicron strains were comprised of 8 BA.1.1 (21 K), 27 BA.2 (21 L), and 1 BA.2.12.1 (22C). Phylogenetic analysis of the identified isolates and representative sequences of SARS-CoV-2 strains revealed clusters that presented the WHO VOCs. Specific or unique mutations for each VOC waxed and waned according to the variant waves. Our findings allowed recognition of the overall trends of SARS-CoV-2 isolates, which implicated replication advantage, immune evasion, and disease management.

A New Strategy for Evaluating the Quality of Laboratory Results for Big Data Research: Using External Quality Assessment Survey Data (2010-2020).

Background: To ensure valid results of big data research in the medical field, the input laboratory results need to be of high quality. We aimed to establish a strategy for evaluating the quality of laboratory results suitable for big data research. Methods: We used Korean Association of External Quality Assessment Service (KEQAS) data to retrospectively review multicenter data. Seven measurands were analyzed using commutable materials: HbA1c, creatinine (Cr), total cholesterol (TC), triglyceride (TG), alpha-fetoprotein (AFP), prostate-specific antigen (PSA), and cardiac troponin I (cTnI). These were classified into three groups based on their standardization or harmonization status. HbA1c, Cr, TC, TG, and AFP were analyzed with respect to peer group values. PSA and cTnI were analyzed in separate peer groups according to the calibrator type and manufacturer, respectively. The acceptance rate and absolute percentage bias at the medical decision level were calculated based on biological variation criteria. Results: The acceptance rate (22.5%-100%) varied greatly among the test items, and the mean percentage biases were 0.6%-5.6%, 1.0%-9.6%, and 1.6%-11.3% for all items that satisfied optimum, desirable, and minimum criteria, respectively. Conclusions: The acceptance rate of participants and their external quality assessment (EQA) results exhibited statistically significant differences according to the quality grade for each criterion. Even when they passed the EQA standards, the test results did not guarantee the quality requirements for big data. We suggest that the KEQAS classification can serve as a guide for building big data.

Comparison of Nasal Swabs, Nasopharyngeal Swabs, and Saliva Samples for the Detection of SARS-CoV-2 and other Respiratory Virus Infections.

Background: Nasal swabs and saliva samples are being considered alternatives to nasopharyngeal swabs (NPSs) for detecting severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2); however, few studies have compared the usefulness of nasal swabs, NPSs, and saliva samples for detecting SARS-CoV-2 and other respiratory virus infections. We compared the positivity rates and concentrations of viruses detected in nasal swabs, NPSs, and saliva samples using cycle threshold (Ct) values from real-time PCR tests for respiratory viruses. Methods: In total, 236 samples (48 five-rub and 10 10-rub nasal swabs, 96 NPSs collected using two different products, 48 saliva swabs, and 34 undiluted saliva samples) from 48 patients (34 patients with SARS-CoV-2 and 14 with other respiratory virus infections) and 40 samples from eight healthy controls were obtained. The PCR positivity and Ct values were compared using Allplex Respiratory Panels 1/2/3 and Allplex SARS-CoV-2 real-time PCR. Results: NPSs showed the lowest Ct values (indicating the highest virus concentrations); however, nasal and saliva samples yielded positive results for SARS-CoV-2 and other respiratory viruses. The median Ct value for SARS-CoV-2 E gene PCR using nasal swab samples collected with 10 rubs was significantly different from that obtained using nasal swabs collected with five rubs (Ct=24.3 vs. 28.9; P=0.002), but not from that obtained using NPSs. Conclusions: Our results confirm that the NPS is the best sample type for detecting respiratory viruses, but nasal swabs and saliva samples can be alternatives to NPSs. Vigorously and sufficiently rubbed nasal swabs can provide SARS-CoV-2 concentrations similar to those obtained with NPSs.