Coagulation Testing in Real-World Setting: Insights From a Comprehensive Survey.

The objective of this survey was to gain a real-world perspective on coagulation testing by evaluating the availability of various coagulation laboratory tests, assessing specific analytic and postanalytic steps in clinical laboratories in Korea.Participants were surveyed using a 65-question questionnaire specifically focused on their coagulation testing practices related to prothrombin time (PT), activated partial thromboplastin time (aPTT), plasma-mixing studies, lupus anticoagulant (LA) tests, platelet function tests, coagulation factor assays, and the composition of hemostasis and thrombosis test panels. The survey was performed between July and September 2022.The survey achieved a 77.9% (81 of 104) response rate. PT or aPTT tests were performed directly at all participating institutions, followed by D-dimer and fibrinogen tests, platelet function test, and plasma-mixing studies in order of frequency. Variations existed in the performance of mixing test and LA assessment. Patterns of coagulating testing differed depending on the size of the hospital. The survey revealed that most laboratories conducted coagulation tests following the international guidelines such as Clinical Laboratory Standards Institute guidelines and the Korean Laboratory Certification system. However, some coagulation tests, including mixing test and LA tests, are yet to be standardized in Korea.Continuous education on coagulation test methods and internal and external quality control are required to encourage laboratories to enhance the performance of coagulation testing.

Machine Learning Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy for ER+HER2- Breast Cancer: Integrating Tumoral and Peritumoral MRI Radiomic Features.

BACKGROUND: This study aimed to predict pathologic complete response (pCR) in neoadjuvant chemotherapy for ER+HER2- locally advanced breast cancer (LABC), a subtype with limited treatment response. METHODS: We included 265 ER+HER2- LABC patients (2010-2020) with pre-treatment MRI, neoadjuvant chemotherapy, and confirmed pathology. Using data from January 2016, we divided them into training and validation cohorts. Volumes of interest (VOI) for the tumoral and peritumoral regions were segmented on preoperative MRI from three sequences: T1-weighted early and delayed contrast-enhanced sequences and T2-weighted fat-suppressed sequence (T2FS). We constructed seven machine learning models using tumoral, peritumoral, and combined texture features within and across the sequences, and evaluated their pCR prediction performance using AUC values. RESULTS: The best single sequence model was SVM using a 1 mm tumor-to-peritumor VOI in the early contrast-enhanced phase (AUC = 0.9447). Among the combinations, the top-performing model was K-Nearest Neighbor, using 1 mm tumor-to-peritumor VOI in the early contrast-enhanced phase and 3 mm peritumoral VOI in T2FS (AUC = 0.9631). CONCLUSIONS: We suggest that a combined machine learning model that integrates tumoral and peritumoral radiomic features across different MRI sequences can provide a more accurate pretreatment pCR prediction for neoadjuvant chemotherapy in ER+HER2- LABC.

The Impact Evaluation of Acid Mine Drainage on Zebrafish (Danio rerio) and Water Fleas (Daphnia magna) in the Vicinity of the Geum River Basin in Korea.

Heavy metals, such as copper, lead, and cadmium, carried by acid mine drainage are pollutants of the aquatic ecosystem, posing a significant health risk to the water resource for humans. Environmental technologies to reduce metal contamination are applied for post-mining prevention and improvement. Despite detailed pollution management, water contaminated by heavy metals still flows into the natural water system. This study investigated the impact of drainage discharged from abandoned mines near the major river in South Korea on aquatic organisms. The toxicity of the field water showed a more significant effect than observed through the experiment for each heavy-metal concentration. Various toxic substances coexisted in the field water around the mine, such that the overall toxic intensity was high even when the concentration of each heavy metal was low. As a result, the inhibition of activity of aquatic organisms was observed at low individual concentrations, and further investigation on the effect of long-term exposure to trace amounts of heavy metals is required.

Characteristics of Korean BCR-ABL1-Negative Myeloproliferative Neoplasms Related to the 2016 WHO Criteria Revision.

BACKGROUND: We aimed to identify changes in the diagnosis and subtype classification of Korean patients with BCR-ABL1-negative MPN related to the revision of the WHO classification in 2016. METHODS: We evaluated 76 Korean patients with BCR-ABL1-negative MPN who underwent diagnostic work-ups, including bone marrow (BM) examinations and JAK2 V617F mutation analysis, from January 2013 to June 2018. Additionally, we reclassified the subtype of 43 patients who were diagnosed based on the WHO 2008 classification. RESULTS: From January 2013 to April 2016, 43 patients were diagnosed with BCR-ABL1-negative MPN (12 PV, 17 ET, 14 PMF) according to the 2008 WHO classification, and from May 2016 to June 2018, 33 patients were diagnosed according to the 2016 classification (15 PV, 11 ET, 7 PMF). With the application of 2016 classification, 3 cases of ET were reclassified as pre-PMF, and the proportion of PV increased from 27.9% to 45.5%. There were significant differences in CBC between pre-PMF and overt PMF, between ET and overt-PMF, but no difference between ET and pre-PMF. CONCLUSIONS: The overall characteristics of BCR-ABL1-negative MPN patients were not significantly different from those of previous reports. 'Masked PV', which could not be diagnosed according to the WHO 2008 classification, may have been diagnosed as PV since 2016 due to the increase in the diagnostic value of the BM findings and the lowering of the hemoglobin (Hb) threshold.

Voxel-wise partial volume correction method for accurate estimation of tissue sodium concentration in 23 Na-MRI at 7 T.

Sodium is crucial for the maintenance of cell physiology, and its regulation of the sodium-potassium pump has implications for various neurological conditions. The distribution of sodium concentrations in tissue can be quantitatively evaluated by means of sodium MRI (23 Na-MRI). Despite its usefulness in diagnosing particular disease conditions, tissue sodium concentration (TSC) estimated from 23 Na-MRI can be strongly biased by partial volume effects (PVEs) that are induced by broad point spread functions (PSFs) as well as tissue fraction effects. In this work, we aimed to propose a robust voxel-wise partial volume correction (PVC) method for 23 Na-MRI. The method is based on a linear regression (LR) approach to correct for tissue fraction effects, but it utilizes a 3D kernel combined with a modified least trimmed square (3D-mLTS) method in order to minimize regression-induced inherent smoothing effects. We acquired 23 Na-MRI data with conventional Cartesian sampling at 7 T, and spill-over effects due to the PSF were considered prior to correcting for tissue fraction effects using 3D-mLTS. In the simulation, we found that the TSCs of gray matter (GM) and white matter (WM) were underestimated by 20% and 11% respectively without correcting tissue fraction effects, but the differences between ground truth and PVE-corrected data after the PVC using the 3D-mLTS method were only approximately 0.6% and 0.4% for GM and WM, respectively. The capability of the 3D-mLTS method was further demonstrated with in vivo 23 Na-MRI data, showing significantly lower regression errors (ie root mean squared error) as compared with conventional LR methods (p < 0.001). The results of simulation and in vivo experiments revealed that 3D-mLTS is superior for determining under- or overestimated TSCs while preserving anatomical details. This suggests that the 3D-mLTS method is well suited for the accurate determination of TSC, especially in small focal lesions associated with pathological conditions.

Efficacy of in situ well-based denitrification bio-barrier (WDB) remediating high nitrate flux in groundwater near a stock-raising complex.

This study assessed the feasibility of an in situ well-based denitrification bio-barrier (WDB) for managing groundwater contaminated with high-strength nitrate. To evaluate the efficacy of WDB using fumarate as a carbon source and/or electron donor, three sequential single-well push-pull tests (SWPPTs) were conducted at six test sites. The values of the isotope enrichment factor (ɛ) ranging from -6.5‰ to -22.6‰ and the detection and degradation of nitrite and nitrous oxide confirmed complete in situ denitrification of nitrate to nitrogen gas. The ratio of the first-order rate coefficient of fumarate to nitrate (k1,fum/k1,NO3) was obtained to estimate the amount and frequency of fumarate injection for the effective design of WDB. At three sites, the ratios ranged from 0.67 to 0.80, while the other two sites showed higher ratios of 2.97 and 2.20 than the theoretical values and significant amounts of sulfate reduction, theoretically equivalent to 6.5% of total fumarate consumption. Considering the theoretical mole ratio of fumarate to nitrate of 0.98, the amount and frequency of fumarate injection is site specific. During the operating WDB, the average annual nitrate mass degraded (95% CI) was 2.2 ± 1.0 kg N/yr/well. The amount of N reduced by one well of WDB is equivalent to treating 110 m3 of groundwater at 30 mg N/L to the level of 10 mg N/L for one year. WDB would be an effective remediation option for managing high nitrate flux in groundwater.

Electron-Lattice Coupling in Correlated Materials of Low Electron Occupancy.

In correlated materials including transition metal oxides, electronic properties and functionalities are modulated and enriched by couplings between the electron and lattice degrees of freedom. These couplings are controlled by external parameters such as chemical doping, pressure, magnetic and electric fields, and light irradiation. However, the electron-lattice coupling relies on orbital characters, i.e., symmetry and occupancy, of t2g and eg orbitals, so that a large electron-lattice coupling is limited to eg electron system, whereas t2g electron system exhibits an inherently weak coupling. Here, we design and demonstrate a strongly enhanced electron-lattice coupling in electron-doped SrTiO3, that is, the t2g electron system. In ultrathin films of electron-doped SrTiO3 [i.e., (La0.25Sr0.75)TiO3], we reveal the strong electron-lattice-orbital coupling, which is manifested by extremely increased tetragonality and the corresponding metal-to-insulator transition. Our findings open the way of an active tuning of the charge-lattice-orbital coupling to obtain new functionalities relevant to emerging nanoelectronic devices.

Evaluation of LABType® SSO HLA Typing using the Luminex Platform: Cord Blood Registry Typing for the Korean Population.

BACKGROUND: The performance of a new intermediate-resolution method using a PCR-Luminex platform and LABType® SSO A, B DRB1 kits as an HLA typing method for the cord blood (CB) registry of the Korean population was investigated. METHODS: A total of 1,413 cord blood units (CBUs) were enrolled - 1,382 from Koreans and 31 from non-Koreans or mixed-ancestry individuals. HLA-A, -B, and -DRB1 typing was performed using the LABType® SSO typing kits. HLA typing with the DNA method and 2-digit results are mandatory for the public CB bank in Korea according to the "CB Act." RESULTS: The proportions of ambiguous results in the 2-digit assignment were 14.6% (206/1,413) and 14.8% (205/ 1,382) among the total subjects and the Korean donors, respectively. In the 2-digit resolution, 3 different HLA-A types (69 CBUs), 31 HLA-B types (124 CBUs), and 3 HLA-DRB1 types (13 CBUs) showed ambiguous results. The 'most probable type' to the ambiguous results based on the reported Korean HLA allele frequencies were able to be assigned. The most probable results were 100% consistent with the confirmed types as determined by the HD kits (DRB1) and additional PCR-SBT or PCR-SSP tests (A and B). Luminex technology is more automated and less labor intensive than the conventional SSO typing method, and the results are less affected by differences between inspectors. CONCLUSIONS: Although it is not satisfactory as a sole confirmation test and cannot be used as a replacement for the PCR-SBT test, the combination of Luminex technology with LABType® SSO kits and population frequency data provides a proper typing platform that can be used as a qualifying test for CB registries.

Stiffness measurement using terahertz and acoustic waves for biological samples.

A method is proposed to measure sample stiffness using terahertz wave and acoustic stimulation. The stiffness-dependent vibration is measured using terahertz wave (T-ray) during an acoustic stimulation. To quantify the vibration, time of the peak amplitude of the reflected T-ray is measured. In our experiment, the T-ray is asynchronously applied during the period of the acoustic stimulation, and multiple measurements are taken to use the standard deviation and the maximum difference in the peak times to estimate the amplitude of the vibration. Some preliminary results are shown using biological samples.

Setting the Gray Zone of Near-Cutoff Values in a Real-Time PCR Test for the Detection of Mycobacterium tuberculosis in an Intermediate Burden Country.

BACKGROUND: Recently, molecular detection of Mycobacterium tuberculosis in a respiratory specimens is accepted as one of the standard procedures for diagnosis of tuberculosis in Korea. When detecting tuberculosis using a real-time polymerase chain reaction (PCR), results showed the repeated near-cutoff values in a specimen make it difficult for the laboratory to give definitive reports as positive or negative. METHODS: We retrospectively evaluated clinical state of ninety-eight patients who were not currently taking antituberculosis medications and had near-cutoff values of respiratory specimens using a real-time PCR test. RESULTS: Sixty-eight percent of the patients had clinical tuberculosis. In subgroup analysis, patients less than the age of 50, 94.3% had tuberculosis while only 55.6% of the patients with the age of equal and over 50 had tuberculosis (p < 0.001). CONCLUSIONS: Setting a gray zone for real-time PCR result and give additional tailored information onto the interpretative report would be suggested for the clinical practice in an intermediate burden of tuberculosis country.

Field inhomogeneity correction using partial differential phases in magnetic resonance imaging.

Correction of an inhomogeneous magnetic field is proposed using partial differential phases in magnetic resonance imaging. Estimation of the inhomogeneous magnetic field from a measured phase is not an easy task due to phase wrapping and chemical-dependent phase shifts. Using the proposed partial differential phase technique, such problems are resolved. The proposed technique uses most of the 3D pixel data regardless of chemical compounds for the estimation of the inhomogeneous magnetic field. A large number of partial difference data compared to the number of expansion terms for the model of inhomogeneous magnetic field provides a very stable estimation, robust to noise. The technique is applicable to in vivo shimming, water-fat imaging, eddy current compensation, and most phase-related measurements and imaging. The efficacy of the proposed technique is demonstrated with in vivo water-fat imaging.

The value of plasma osteopontin levels as a predictive factor of disease stage and recurrence in patients with bladder urothelial carcinoma: a prospective study.

This study was performed in order to determine the value of plasma osteopontin (OPN) levels as a predictive factor of disease stage and recurrence in patients with bladder urothelial carcinoma (UC). Data from 50 patients diagnosed to have bladder UC after transurethral resection of bladder tumor (TURBT) from 2009 to 2010 were evaluated prospectively. Blood tests were performed before and after TURBT, and plasma OPN levels were measured using enzyme-linked immunosorbent assay. Differences in OPN levels according to clinicopathologic variables were analyzed statistically. Significant differences in plasma OPN levels were observed between groups with and without muscle invasion (89.16 vs. 67.08 ng/mL, p=0.041). Comparison according to tumor grade found no significant difference between high and low grade groups (p=0.115). Mean plasma OPN levels decreased after TURBT without statistical significance (p=0.571). Between groups with recurrence and those without recurrence, OPN levels of the group with recurrence were higher without statistical significance (p=0.161). Comparison of plasma OPN levels according to performance of radical cystectomy (RC) showed significant differences; patients who underwent RC showed higher levels of plasma OPN (95.58 vs. 70.37 ng/mL, p=0.030). Comparison according to T stage after RC showed significant differences in OPN levels (T1: 67.45, T2: 86.60 and T3: 95.23 ng/mL, respectively, p=0.006). The group with lymph node invasion showed significantly higher levels of OPN, compared to the group without invasion (153.24 vs. 68.03 ng/mL, p=0.017). Preoperative plasma OPN levels correlated to muscle invasion of bladder UC and pathological stage after RC.

A Case of Bladder Cancer Found during a Workup for Urge Incontinence.

Irritative urinary symptoms may suggest the possibility of bladder cancer. We report a case of metastatic bladder cancer that was discovered during a workup for urge incontinence in a 65-year-old woman with a history of stomach cancer. She had a medical history of gastrectomy due to stomach cancer 4 years previously. The patient complained of urgency unresponsive to anticholinergic therapy. Cystoscopy revealed the presence of suspicious bladder mucosal lesions that were biopsied. The pathology was consistent with metastatic signet-ring cell adenocarcinoma. This case suggests that irritative urinary symptoms can be the first clinical manifestation in patients with bladder cancer.

Standardization of terminology in laboratory medicine II.

Standardization of medical terminology is essential in data transmission between health care institutes and in maximizing the benefits of information technology. The purpose of this study was to standardize medical terms for laboratory observations. During the second year of the study, a standard database of concept names for laboratory terms that covered those used in tertiary health care institutes and reference laboratories was developed. The laboratory terms in the Logical Observation Identifier Names and Codes (LOINC) database were adopted and matched with the electronic data interchange (EDI) codes in Korea. A public hearing and a workshop for clinical pathologists were held to collect the opinions of experts. The Korean standard laboratory terminology database containing six axial concept names, components, property, time aspect, system (specimen), scale type, and method type, was established for 29,340 test observations. Short names and mapping tables for EDI codes and UMLS were added. Synonym tables were prepared to help match concept names to common terms used in the fields. We herein described the Korean standard laboratory terminology database for test names, result description terms, and result units encompassing most of the laboratory tests in Korea.

Salsolinol, an endogenous neurotoxin, enhances platelet aggregation and thrombus formation.

Salsolinol, an endogenous neurotoxin, is known to be involved in the neuropathy of Parkinson's disease and chronic alcoholism. In these diseases, increased thrombotic events are also commonly reported, yet the mechanism underlying remains poorly understood. Here we report that salsolinol can enhance agonist-induced platelet aggregation and granular secretion, which is essential in the thrombus formation. In rat and human platelets, agonist-induced platelet aggregation was significantly increased by salsolinol in a concentration-dependent manner. Agonist-induced granular secretions of serotonin and concomitant P-selectin expression were also augmented by salsolinol. alpha2-adrenergic blockers attenuated the salsolinol-enhanced aggregation and the inhibition of cyclic AMP generation was found, suggesting the involvement of alpha2-adrenergic receptor-mediated pathways in these events. In accord with the in-vitro results, in an arterial and venous thrombosis model in vivo in the rat, salsolinol shortened vessel occlusion time and increased thrombus formation, respectively. In conclusion, we demonstrated that salsolinol can enhance agonist-induced aggregation and granular secretion in platelets through alpha2-adrenergic receptor activation, which resulted in the increased thrombus formation in vivo. These results suggest that salsolinol-enhanced platelet aggregation could be a possible contributing factor to the thrombotic events observed in Parkinson's disease and alcoholism.

Protective role of CYP1A1*2A in the development of multiple myeloma.

We had previously reported the association of the NQO1*2/*2 polymorphism with a decreased risk for multiple myeloma (MM) in Koreans (odds ratio, OR, 0.24; 95% confidence interval, CI, 0.01-0.68). The associations of polymorphisms of other metabolizing enzymes (CYP1A1, GSTM1 and GSTT1) with the MM risk were investigated in 116 Korean MM patients and 176 Korean controls using TaqMan allelic discrimination and multiplex polymerase chain reaction. The ORs for CYP1A1*1/*2A and CYP1A1*1/*2B genotypes were 0.43 (95% CI, 0.19-0.98) and 0.51 (95% CI, 0.26-0.98), respectively, which was significantly associated with a decreased MM risk. With regard to CYP1A1 alleles, the OR for the CYP1A1*2A allele was 0.57 (95% CI, 0.326-0.995), which was also significantly associated with a decreased MM risk. However, null types of GSTM1 and GSTT1 polymorphisms were not associated with the MM risk. These results were different from those of a previous report on Caucasians which suggested the association of the GSTT1 polymorphism with an increased MM risk and no association of CYP1A1 with the MM risk. The associations of polymorphisms of metabolizing enzymes with the risk for MM differed between Koreans and Caucasians, suggesting an ethnic variation in the susceptibility to MM.

Tumor necrosis factor alpha promoter polymorphism associated with increased susceptibility to secondary hemophagocytic lymphohistiocytosis in the Korean population.

Secondary hemophagocytic lymphohistiocytosis (HLH) can be associated with various diseases including infections and lymphoma. The clinical findings of HLH can be explained by an increased production of cytokines such as tumor necrosis factor alpha (TNF-alpha). As not all the patients with infection or lymphoma have secondary HLH, we investigated the relationship between susceptibility to secondary HLH and TNF-alpha promoter polymorphisms to identify genetic factors of secondary HLH. We determined the alleles of four promoter sites (-1031/-857/-308/-238) of TNF-alpha gene by using Taqman-based allelic discrimination assays in the 66 Korean patients with secondary HLH and 100 healthy Korean controls. We found that the frequency of the TNF-alpha -1031C allele, which is associated with higher-plasma TNF-alpha levels, was enriched in patients with secondary HLH compared with healthy controls (OR=2.00, 95% CI 1.20-3.30, P=0.007). In haplotype analysis of TNF-alpha polymorphisms, the haplotype H6 (CTGG) was detected only in the patient group, and the haplotype group (H2 or H5 or H6) including TNF-alpha -1031C allele was overexpressed in secondary HLH patients (OR=2.52, 95% CI 1.33-4.77, P=0.004). These results suggested that TNF-alpha -1031C allele and its associated haplotypes in Koreans may enhance susceptibility to secondary HLH.

Type II collagen autoimmunity in rheumatoid arthritis.

This review summarizes the autoimmune reaction to type II collagen (CII) autoimmunity with regard not only to antibody response to CII but also to the clinical significance or biological characteristics of the CII-reactive T cell, focusing on studies of human RA rather than on animal models. The authors investigated the effect of the interaction between CII-reactive T cells and fibroblast-like synoviocytes (FLSs) on the production of inflammatory cytokines. When the CII-reactive T cells were co-cultured with FLS, the production of interleukin-15 and tumor necrosis factor-alpha from FLSs were significantly increased, and this increase was clearly presented in accord with the expansion of CII-reactive T cells. In addition, the production of interferon-gamma and interleukin-17, T cell-derived cytokines, was increased by the co-incubation of CII-reactive T cells with FLSs. When FLSs were co-cultured with CII-stimulated T cells, the production of interleukin-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha was significantly enhanced. The increased production of these chemokines was strongly correlated with an increase in T-cell response to CII. Conclusively, high reactivity to CII was frequently found in RA patients. Enhanced T-cell responses to CII were associated with increased production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. Interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, the authors' recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but also in the amplification and perpetuation of the inflammatory process in RA.