Dynamic Response of Musclin, a Myokine, to Aerobic Exercise and Its Interplay with Natriuretic Peptides and Receptor C.

OBJECTIVES: Musclin, recently identified as a myokine, has been recognized for its physiological significance in potentiating the functional properties of natrieutic peptides (NPs) through competitive inhibition of their clearance receptor, natrieutic peptide receptor C (NPR-C). This study, for the first time in the literature, investigated the dynamic response of musclin during and after aerobic exercise in humans, exploring its potential as a myokine and its interaction with NPs and NPR-C in the context of exercise-induced metabolic responses. METHODS: Twenty-one inactive young males participated, and we assessed changes in serum levels of musclin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), epinephrine (Epi), and glycerol as an indicative of lipid mobilization, during and after moderate-intensity aerobic exercise. Furthermore, we evaluated the gene expression of NPR-C in subcutaneous fat biopsies. RESULTS: Serum musclin levels increased significantly during aerobic exercise, followed by a decline during recovery, remaining elevated compared to baseline. Significant correlations were found between musclin responses and lean body mass (LBM), indicating its regulation by skeletal muscle mass and exercise. Exercise-induced changes in musclin positively correlated with those of ANP, potentially preventing ANP degradation. Additionally, a potential interplay between NPR-C expression and musclin dynamics on ANP was suggested. However, musclin's influence on lipid mobilization was not predominant when considering other lipolytic factors during exercise. DISCUSSION: Musclin's classification as a myokine is supported by its response to aerobic exercise and its association with LBM. Additionally, its interactions with NPR-C and NPs suggest its physiological relevance and potential clinical implications.

Neoadjuvant Chemotherapy Response in Triple-Negative Apocrine Carcinoma: Comparing Apocrine Morphology, Androgen Receptor, and Immune Phenotypes.

CONTEXT.­: Apocrine differentiation and androgen receptor (AR) positivity represent a specific subset of triple-negative breast cancer (TNBC) and are often considered potential prognostic or predictive factors. OBJECTIVE.­: To evaluate the response of TNBC to neoadjuvant chemotherapy (NAC) and to assess the impact of apocrine morphology, AR status, Ki-67 labeling index (Ki-67LI), and tumor-infiltrating lymphocytes (TILs). DESIGN.­: A total of 232 TNBC patients who underwent NAC followed by surgical resection in a single institute were analyzed. The study evaluated apocrine morphology and AR and Ki-67LI expression via immunohistochemistry from pre-NAC biopsy samples. Additionally, pre-NAC intratumoral TILs and stromal TILs (sTILs) were quantified from biopsies using a deep learning model. The response to NAC after surgery was assessed based on residual cancer burden. RESULTS.­: Both apocrine morphology and high AR expression correlated with lower Ki-67LI (P < .001 for both). Apocrine morphology was associated with lower postoperative pathologic complete response (pCR) rates after NAC (P = .02), but the difference in TILs between TNBC cases with and without apocrine morphology was not statistically significant (P = .09 for sTILs). In contrast, AR expression did not significantly affect pCR (P = .13). Pre-NAC TILs strongly correlated with postoperative pCR in TNBCs without apocrine morphology (P < .001 for sTILs), whereas TNBC with apocrine morphology demonstrated an indeterminate trend (P = .82 for sTILs). CONCLUSIONS.­: Although TIL counts did not vary significantly based on apocrine morphology, apocrine morphology itself was a more reliable predictor of NAC response than AR expression. Consequently, although apocrine morphology is a rare subtype of TNBC, its identification is clinically important.

Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults.

BACKGROUND AND OBJECTIVES: Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy. METHODS: Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years. RESULTS: The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio (HR), 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups. CONCLUSIONS: Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.

Prediction of Oncotype DX Recurrence Score Based on Systematic Evaluation of Ki-67 Scores in Hormone Receptor-Positive Early Breast Cancer.

PURPOSE: Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods. METHODS: We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established. RESULTS: Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%. CONCLUSION: We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing.

Usefulness of the MFIS-K, FSS, and FACIT-F Fatigue Scales in Korean Patients With MS, NMOSD, and MOGAD.

BACKGROUND AND PURPOSE: Fatigue is common in demyelinating disorders of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aimed to validate the usefulness of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Fatigue Severity Scale (FSS) relative to the Korean version of the Modified Fatigue Impact Scale (MFIS-K) in Korean patients with MS, NMOSD, and MOGAD. METHODS: There were 294 patients with MS (n=120), NMOSD (n=103), or MOGAD (n=71) enrolled in a prospective demyelinating CNS registry. Fatigue was measured using the FACIT-F, MFIS-K, and FSS. Sleep quality, quality of life, depression, and pain were evaluated using the Pittsburgh Sleep Quality Index (PSQI), 36-item Short-Form Survey (SF-36), and Beck Depression Inventory-II (BDI-II). RESULTS: The MFIS-K, FACIT-F, and FSS scores showed high internal consistencies and strong correlations with each other in the MS, NMOSD, and MOGAD groups. The scores on all three fatigue scales were correlated with PSQI, SF-36, and BDI-II results in the three groups. The areas under the receiver operating characteristic curves for the FSS and FACIT-F were 0.834 and 0.835, respectively, for MS, 0.877 and 0.833 for NMOSD, and 0.925 and 0.883 for MOGAD. CONCLUSIONS: These results suggest that the MFIS-K, FSS, and FACIT-F are useful and valuable assessment instruments for evaluating fatigue in Korean patients with MS, NMOSD, and MOGAD.

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.

PHD2 enzyme is an intracellular manganese sensor that initiates the homeostatic response against elevated manganese.

Intracellular sensors detect changes in levels of essential metals to initiate homeostatic responses. But, a mammalian manganese (Mn) sensor is unknown, representing a major gap in understanding of Mn homeostasis. Using human-relevant models, we recently reported that: 1) the primary homeostatic response to elevated Mn is upregulation of hypoxia-inducible factors (HIFs), which increases expression of the Mn efflux transporter SLC30A10; and 2) elevated Mn blocks the prolyl hydroxylation of HIFs by prolyl hydroxylase domain (PHD) enzymes, which otherwise targets HIFs for degradation. Thus, the mammalian mechanism for sensing elevated Mn likely relates to PHD inhibition. Moreover, 1) Mn substitutes for a catalytic iron (Fe) in PHD structures; and 2) exchangeable cellular levels of Fe and Mn are comparable. Therefore, we hypothesized that elevated Mn directly inhibits PHD by replacing its catalytic Fe. In vitro assays using catalytically active PHD2, the primary PHD isoform, revealed that Mn inhibited, and Fe supplementation rescued, PHD2 activity. However, a mutation in PHD2 (D315E) that selectively reduced Mn binding without substantially impacting Fe binding or enzymatic activity resulted in complete insensitivity of PHD2 to Mn in vitro. Additionally, hepatic cells expressing full-length PHD2D315E were less sensitive to Mn-induced HIF activation and SLC30A10 upregulation than PHD2wild-type. These results: 1) define a fundamental Mn sensing mechanism for controlling Mn homeostasis-elevated Mn inhibits PHD2, which functions as a Mn sensor, by outcompeting its catalytic Fe, and PHD2 inhibition activates HIF signaling to up-regulate SLC30A10; and 2) identify a unique mode of metal sensing that may have wide applicability.

Protective Effect of Red Light-Emitting Diode against UV-B Radiation-Induced Skin Damage in SKH:HR-2 Hairless Mice.

In this in vivo study on hairless mice, we examined the effects of light-emitting diode (LED) treatment applied prior to ultraviolet B (UVB) irradiation. We found that pre-treating with LED improved skin morphological and histopathological conditions compared to those only exposed to UVB irradiation. In our study, histological evaluation of collagen and elastic fibers after LED treatment prior to UVB irradiation showed that this pretreatment significantly enhanced the quality of fibers, which were otherwise poor in density and irregularly arranged due to UV exposure alone. This suggests that LED treatment promotes collagen and elastin production, leading to improved skin properties. Additionally, we observed an increase in Claudin-1 expression and a reduction in nuclear factor-erythroid 2-related factor 2 (Nrf-2) and heme-oxygenase 1 (HO-1) expression within the LED-treated skin tissues, suggesting that LED therapy may modulate key skin barrier proteins and oxidative stress markers. These results demonstrate that pretreatment with LED light can enhance the skin's resistance to UVB-induced damage by modulating gene regulation associated with skin protection. Further investigations are needed to explore the broader biological effects of LED therapy on other tissues such as blood vessels. This study underscores the potential of LED therapy as a non-invasive approach to enhance skin repair and counteract the effects of photoaging caused by UV exposure.

Constructing Reversible Li Deposition Interfaces by Tailoring Lithiophilic Functionalities of a Heteroatom-Doped Graphene Interlayer for Highly Stable Li Metal Anodes.

Lithium (Li) metal has been regarded as the ideal anode for rechargeable batteries due to its low reduction potential and high theoretical capacity. However, the formation of fatal Li dendrites during repeated cycling shortens the battery life and causes serious safety concerns. Functionalized separators with electrically conductive and lithiophilic coating layers potentially inhibit dendrite formation and growth on Li metal anodes by providing nucleation sites for reversible Li deposition/stripping. In this work, we propose functionalized separators incorporating heteroatom-doped (N or B) graphene interlayers to modulate the Li nucleation behavior. The electronegative N-doping and electropositive B-doping were investigated to understand their regulation of the Li deposition behavior. With the heteroatom-doped graphene-coated separators, we observe significantly improved cycling stability along with enhanced charge transfer kinetics and low Li nucleation overpotential. This is attributed to the heteroatom-doped graphene interlayer expanding the surface area of the Li metal anode while providing additional space for uniform Li deposition/stripping, thus preventing undesirable side reactions. As a result, the formation of dendrites and pits on the Li metal anode surface is suppressed, demonstrating the protective effect of the Li metal anode. Interestingly, N-doped graphene-coated separators exhibit lower Li nucleation overpotentials than B-doped graphene-coated separators but rather lower average Coulombic efficiencies and reduced cycling stability. This implies that adequate adsorption on B-based sites, as opposed to the strong adsorption on N-based sites, improves the reversibility. Notably, the Li adsorption strength of the lithiophilic functional groups critically affects the reversibility, as observed by Li nucleation barrier measurements and atomistic simulations. This work suggests that interface engineering using conductive and lithiophilic materials can be a promising strategy for controlling Li deposition in advanced Li metal batteries.

Migraine Risk in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Nationwide Cohort Study in South Korea.

INTRODUCTION: Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. METHODS: This study analyzed claims data from 1492 patients with MS and 1551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged <20 years and with previous migraine were excluded. RESULTS: Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15-1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95%CI: 0.87-1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction=0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. CONCLUSION: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.

Nickel-Catalyzed Double Deoxygenative C-N Coupling of Acyloxyamines.

A double deoxygenative C-N coupling protocol has been developed by employing acyloxyamines through N-O bond activation. The C-N bond formation under mild reaction conditions, employing NiCl2 as the catalyst and cataCXiumA as a ligand, results in the production of a diverse array of alkylated secondary or tertiary amines, including heterocyclic amines. This method introduces a novel catalytic strategy that emphasizes the versatility of nickel-catalyzed reactions, extending beyond traditional synthetic boundaries.

Analysis of the efficacy of retrodiscal approach percutaneous epidural adhesiolysis with WHIP catheter® in patients with lumbar radiculopathy: A retrospective study.

Percutaneous epidural adhesiolysis (PEA) is an effective treatment for patients with lumbar radiculopathy unresponsive to single steroid injections. Various approaches and instruments have been developed to access these lesions. This study aimed to evaluate the utility of a retrodiscal approach for epidural adhesiolysis using a WHIP catheter®. This retrospective study was conducted at Bundang Seoul National University Hospital, reviewing cases from January to December 2022. Forty-seven patients diagnosed with lumbar radiculopathy, aged 20 to 80 years, who underwent PEA with the WHIP catheter® were included. Outcomes assessed Numeric Rating Scale (NRS) for pain, Patients' Global Impression of Change (PGIC) scores, and the incidence of procedure-related complications. Follow-up evaluations occurred at 1, 3, and 6 months post-procedure. Among 47 patients, 41 completed the study, showing significant pain reduction at all follow-up points: 1 month (N = 41, 1.32 ±â€…1.68, P < .001), 3 months (N = 31, 1.90 ±â€…2.14, P < .001), and 6 months (N = 30, 2.50 ±â€…2.30, P < .001). PGIC scores indicated that 40% of the patients reported substantial improvement at one-month post-procedure. The complications were minimal, with only one case of intradiscal injection and 2 cases of vascular uptake. The retrodiscal approach PEA using the WHIP catheter® demonstrated significant efficacy in pain reduction with minimal safety concerns for patients with lumbar radiculopathy. These findings suggest that this procedure is a viable option for patients who are unresponsive to conservative treatment. However, the retrospective nature of this study and its small sample size necessitate further prospective controlled studies to confirm our results and establish long-term outcomes.

Metabolic effects and cardiovascular disease risks of antiviral treatments in patients with chronic hepatitis B.

Different antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)-induced dyslipidemia and its associated outcomes are significant. This study utilized 15-year historical cohort including patients with CHB in Korea and consisted of two parts: the single-antiviral and switch-antiviral cohorts. In the single-antiviral cohort, patients were divided into four groups (entecavir [ETV]-only, tenofovir disoproxil fumarate [TDF]-only, TAF-only, and non-antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch-antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single-antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well-balanced after PSM. Changes in total cholesterol were significantly different between groups (-2.57 mg/dL/year in the TDF-only group and +2.88 mg/dL/year in the TAF-only group; p = 0.002 and p = 0.02, respectively). In the TDF-only group, HDL cholesterol decreased as well (-0.55 mg/dL/year; p < 0.001). The TAF-only group had the greatest increase in ASCVD risk, followed by the TDF-only group and the non-antiviral group. In the switch-antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (-1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (-2.96 mg/dL/year in the TDF-only group and +3.09 mg/dL/year in the TAF-only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin-treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks.

Deep learning model integrating cfDNA methylation and fragment size profiles for lung cancer diagnosis.

Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to distinguish patients with lung cancer from healthy individuals. Additionally, we sought to develop a deep learning model incorporating cfDNA methylation and fragment size profiles. To achieve this, we utilized methylation data collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Then we generated methylated DNA immunoprecipitation sequencing and genome-wide Enzymatic Methyl-seq (EM-seq) form lung cancer tissue and plasma. Using these data, we selected 366 methylation markers. A targeted EM-seq panel was designed using the selected markers, and 142 lung cancer and 56 healthy samples were produced with the panel. Additionally, cfDNA samples from healthy individuals and lung cancer patients were diluted to evaluate sensitivity. Its lung cancer detection performance reached an accuracy of 81.5% and an area under the receiver operating characteristic curve of 0.87. In the serial dilution experiment, we achieved tumor fraction detection of 1% at 98% specificity and 0.1% at 80% specificity. In conclusion, we successfully developed and validated a combination of methylation panel and a deep learning model that can distinguish between patients with lung cancer and healthy individuals.

S2 Peptide-Conjugated SARS-CoV-2 Virus-like Particles Provide Broad Protection against SARS-CoV-2 Variants of Concern.

Approved COVID-19 vaccines primarily induce neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the emergence of variants of concern with RBD mutations poses challenges to vaccine efficacy. This study aimed to design a next-generation vaccine that provides broader protection against diverse coronaviruses, focusing on glycan-free S2 peptides as vaccine candidates to overcome the low immunogenicity of the S2 domain due to the N-linked glycans on the S antigen stalk, which can mask S2 antibody responses. Glycan-free S2 peptides were synthesized and attached to SARS-CoV-2 virus-like particles (VLPs) lacking the S antigen. Humoral and cellular immune responses were analyzed after the second booster immunization in BALB/c mice. Enzyme-linked immunosorbent assay revealed the reactivity of sera against SARS-CoV-2 variants, and pseudovirus neutralization assay confirmed neutralizing activities. Among the S2 peptide-conjugated VLPs, the S2.3 (N1135-K1157) and S2.5 (A1174-L1193) peptide-VLP conjugates effectively induced S2-specific serum immunoglobulins. These antisera showed high reactivity against SARS-CoV-2 variant S proteins and effectively inhibited pseudoviral infections. S2 peptide-conjugated VLPs activated SARS-CoV-2 VLP-specific T-cells. The SARS-CoV-2 vaccine incorporating conserved S2 peptides and CoV-2 VLPs shows promise as a universal vaccine capable of generating neutralizing antibodies and T-cell responses against SARS-CoV-2 variants.

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.

Side- and Sinus-Specific Relationships between Chronic Rhinosinusitis and Ischemic Stroke Using Imaging Analyses.

Recent studies have reported chronic rhinosinusitis (CRS) as an independent risk factor for stroke. However, the association with stroke depending on the affected sinuses has not been explored. This study aimed to elucidate the side- and sinus-specific relationship between CRS and ischemic stroke through imaging analyses. We retrospectively reviewed the medical records of patients who were diagnosed with ischemic stroke at a tertiary center. CRS was defined as having a total score of greater than or equal to 4, according to the Lund-Mackay scoring system, through brain magnetic resonance imaging or computed tomography. We investigated the side- and sinus-specific correlation between CRS and ischemic stroke. Subgroup analyses were performed for different age groups. CRS prevalence in patients with ischemic stroke was 18.4%, which was higher than the previously reported prevalence in the general population. Overall, there was no correlation between the directions of the CRS and ischemic stroke (p > 0.05). When each sinus was analyzed, the frontal (Cramer's V = 0.479, p < 0.001), anterior (Cramer's V = 0.396, p < 0.001)/posterior (Cramer's V = 0.300, p = 0.008) ethmoid, and sphenoid (Cramer's V = 0.383, p = 0.005) sinuses showed a statistically significant correlation with the side of stroke, but the maxillary sinus (Cramer's V = 0.138, p = 0.208) did not. In subgroup analyses, a significant right-side correlation between the two diseases was observed in the older-age subgroup (≥65 years old, Cramer's V = 0.142, p = 0.040). Diabetes mellitus (odds ratio = 1.596, 95% confidence interval = 1.204-2.116) was identified as an independent risk factor for having CRS in patients with ischemic stroke. CRS of the frontal, anterior/posterior ethmoid, and sphenoid sinuses has a directional relationship with ischemic stroke. Our results on which sinuses correlate with stroke advocate for the active surveillance of CRS in patients at high risk of ischemic stroke.

Microbiota Association and Profiling of Gingival Sulci and Root Canals of Teeth with Primary or Secondary/Persistent Endodontic Infections.

INTRODUCTION: Microbiota associated with primary endodontic infection (PEI) and secondary/persistent endodontic infection (SPEI) must be characterized to elucidate pathogenesis in apical periodontitis and bacterial biomarkers identified for diagnostic and therapeutic applications. METHODS: This study analyzed the microbial community profiles of root canals and gingival sulci (sulcus-E) for teeth with PEI (n = 10) or SPEI (n = 10), using the Illumina MiSeq platform. Bacterial samples from gingival sulci (sulcus-C) of healthy contralateral teeth served as controls. RESULTS: There were 15 phyla, 177 genera, and 340 species identified. The number and diversity of bacteria in root canals did not differ significantly between PEI and SPEI. Proteobacteria, Firmicutes, Fusobacteria, Bacteroidetes, and Actinobacteria were the dominant phyla in both groups. At the genus level, Lancefieldella, Bifidobacterium, Stomatobaculum, and Schaalia were enriched in root canals with SPEI. Of significance, Lancefieldella was observed in both root canals and sulcus-E of teeth with SPEI. At the species level, Neisseria macacae, Streptococcus gordonii, Bifidobacterium dentium, Stomatobaculum longum, and Schaalia odontolytica were increased significantly in root canals with SPEI compared to PEI. Oribacterium species, Streptococcus salivarius, Lancefieldella parvula, Prevotella denticola, and Oribacterium asaccharolyticum were more abundant in sulcus-E of teeth with SPEI compared to PEI. CONCLUSIONS: There were distinctive and differing predominant bacterial species associated with the root canals and gingival sulci between teeth with PEI and SPEI. Specific bacteria identified in sulcus-E and root canals of teeth with SPEI could serve as noninvasive diagnostic biomarkers for detecting SPEI.

Dual Photoredox and Nickel Catalysis in Regioselective Diacylation: Exploring the Versatility of Nickel Oxidation States in Allene Activation.

We present a nickel-catalyzed regioselective radical diacylation of allenes with ketoacids to produce 1,4-dione products by dual photoredox and nickel catalysis. This integrated approach merges redox-active oxidative addition and reductive elimination steps with migratory insertion. The acyl radical generated in the photoredox cycle sequentially adds to Ni(I) and Ni(II) intermediates following a Ni(I)-Ni(II)-Ni(II)-Ni(III)-Ni(I) catalytic cycle. This methodology, supported by DFT calculations, demonstrates the potential of nickel catalysis in the creation of complex molecular architectures.