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Abstract High-risk human papillomavirus (HPV) infection is an essential factor for the development of cervical cancer. HPV18 is the second most common carcinogenic HPV type following HPV16, but the lineages of HPV18 have been less well studied than those of HPV 16. The purpose of this study was to analyze the nucleotide variants in the E6, E7, and L1 genes of HPV18, to assess the prevalence of HPV18 variants in Korea and to explore the relationship between HPV18 genetic variants and the risk for cervical cancer. A total of 170 DNA samples from HPV18-positive cervical specimens were collected from women admitted to a secondary referral hospital located in Seoul. Among them, the lineages of the 97 samples could be successfully determined by historical nomenclature. All the studied HPV 18 variants were lineage A. Sublineages A1 and A4 comprised 91.7% (89/97) and 1.0% (1/97), respectively. Sublineages other than A1 or A4 comprised 7.2% (7/97). We identified 15 new nucleotide substitutions among 44 nucleotide substitutions: C158T, T317G, T443G, A560G, A5467G, A5560C, A5678C, A6155G, G6462A, T6650G, G6701A, T6809C, A6823G, T6941C and T6953C. Among them, 6 substitutions at positions 317, 443, 5467, 5560, 6462, and 6823 resulted in amino acid changes (E6: F71L and N113K; L1: H13R, H44P, A345T, and N465S, respectively). The pathologic results were classified as normal in 25.8% (25/97) of the women, atypical squamous cells of undermined significance (ASCUS) in 7.2% (7/97), cervical intraepithelial neoplasia (CIN) 1 in 36.1% (35/97), CIN2/3 in 19.6% (18/97), and carcinoma in 12.4% (12/97). There was no significant association between the HPV18 sublineages and the severity of pathologic lesion or the disease progression. This study is the first to analyze the distribution of HPV18 variants in Korean and to associate the results with pathologic findings. Although the HPV18 variants had no significant effect on the degree and progression of the disease, the newly discovered nonsynonymous mutation in L1 might serve as a database to determine vaccine efficacy in Korean women.

Abstract Background To evaluate the correction differences between vertebra and tumor matching as cone‐beam computed tomography (CBCT)‐guided setup strategies in lung stereotactic body radiation therapy (SBRT), and the correlations with tumor characteristics such as size, mobility, and location. Methods The manual registrations for 33 lung tumors treated with SBRT were retrospectively performed by matching thoracic vertebrae for vertebra matching and then by matching CBCT‐visualized tumors within the internal target volume obtained from a four‐dimensional CT dataset for tumor matching. Results The mean correction difference between the two matching methods during the SBRT fractions was larger in the anterior‐posterior direction (2.7 mm) than in the superior‐inferior (2.1 mm) and left‐right (1.4 mm) directions, with differences of less than 5 mm in 90% of the total 134 CBCT fractions. The X‐axis and direct distances from the central axis to the tumor had significant correlations with the correction differences in all three directions, while the mobility‐related parameters were correlated only in the superior‐inferior direction. The absolute differences in lung‐dose parameters after applying the margins (3.4–6.5 mm) required for the setup errors from vertebra matching relative to tumor matching were mild, with values of 1.95 Gy for the mean lung dose and 3.9% for V20. Conclusion The setup differences between vertebra and tumor matching in the CBCT‐guided setup without rotation correction were increased in tumors located long distances from the central axis. The additional safety margins of 3.4–6.5 mm were required for the setup errors from vertebra matching. Key points Significant findings of the study The correction difference between the vertebra and tumor matching as CBCT‐guided setup strategies was the largest in the anterior‐posterior direction and significantly correlated with the X‐axis and direct distances from the central axis to the tumor. What this study adds Setup differences between vertebra and tumor matching in the CBCT‐guided setup were increased in tumors located long distances from the central axis. The additional safety margins of 3.4–6.5 mm were required for the setup errors from vertebra matching.

Facklamia hominis is a facultative anaerobic Grampositive coccus generally displaying weak alpha-hemolysis and negativity for catalase and oxidase. Facklamia species are part of the normal flora of the female genitourinary tract and have been reported in invasive diseases such as meningitis and infective endocarditis, albeit rarely. A 67 year-old-man presented to hospital with a tender, erythematous epidermal cyst on the right side of his upper back. Simple excision of the cyst was performed and the pus was taken with a sterile swab for culture, yielding no growth. One week later, discharge was observed in the patient’s wound site and a sterile swab for culture was taken. The colonies grown were identified as F. hominis by the Vitek 2 system (bioMérieux, France), and the result was then reported to clinicians, and later confirmed by 16S rRNA gene sequencing and matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. To the best of our knowledge, this is the first reported case of F. hominis isolation from a clinical specimen in Korea. (Ann Clin Microbiol 2019;22:50-54)

Abstract Background Detection of central nodes in asymmetrically directed biological networks depends on centrality metrics quantifying individual nodes’ importance in a network. In topological analyses on metabolic networks, various centrality metrics have been mostly applied to metabolite-centric graphs. However, centrality metrics including those not depending on high connections are largely unexplored for directed reaction-centric graphs. Results We applied directed versions of centrality metrics to directed reaction-centric graphs of microbial metabolic networks. To investigate the local role of a node, we developed a novel metric, cascade number, considering how many nodes are closed off from information flow when a particular node is removed. High modularity and scale-freeness were found in the directed reaction-centric graphs and betweenness centrality tended to belong to densely connected modules. Cascade number and bridging centrality identified cascade subnetworks controlling local information flow and irreplaceable bridging nodes between functional modules, respectively. Reactions highly ranked with bridging centrality and cascade number tended to be essential, compared to reactions that other central metrics detected. Conclusions We demonstrate that cascade number and bridging centrality are useful to identify key reactions controlling local information flow in directed reaction-centric graphs of microbial metabolic networks. Knowledge about the local flow connectivity and connections between local modules will contribute to understand how metabolic pathways are assembled.

The use of induced pluripotent stem cells (iPSCs) is an emerging therapeutic option for precision medicine. Cord blood (CB) cells with lower immunogenicity, fewer genomic changes, and persistent epigenetic memory might be ideal candidates for iPSC production. Based on the human leukocyte antigen (HLA) distribution of cord blood units (CBUs) in the public CB bank, we estimated the coverage of the Korean population with HLA-homozygous iPSCs to repurpose cryopreserved CBUs. We analyzed a total of 27,904 Korean CBUs donated to the public CB bank. Low-to-intermediate resolution typing was performed for HLA-A, -B, and -DRB1 alleles, and individuals possessing homozygous HLA haplotypes were identified by direct counting. Moreover, the matching probabilities for zero-mismatch transplantation were calculated for 27,904 CBUs and 50,000,000 potential Korean patients. Among the preserved CBUs, 15 HLA-A, 40 HLA-B, and 13 HLA-DRB1 alleles as well as 48 homozygous HLA-A-B-DRB1 haplotypes were identified at serological equivalents (2 digits). The 48 identified homozygous haplotypes cumulatively matched 78.18% of the 27,904 Korean CB donors as zero HLA-mismatch iPSC sources. Among the combinations of 1,699 haplotypes with frequencies greater than 0.001%, assuming a population of 50 million, those 48 haplotypes can provide a match for 78.37% of potential Korean recipients. A practicable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs may be an efficient option in allogeneic iPSC therapy because this type of haplobanking may provide cell lines with optimal HLA matching for up to three-quarters of the Korean population.

ObjectiveAn interferon-gamma release assay (IGRA) is used to screen for latent tuberculosis infection (LTBI). Among IGRAs, the QuantiFERON-TB Gold In-Tube (QFT-GIT) results are highly variable, so the borderline zone has been proposed to reduce unnecessary LTBI treatment. The aim of this study was to examine the proportion of the borderline zone of QFT-GIT in healthcare workers' (HCWs) serial IGRA and to retrospectively identify the utility of predicting tuberculosis (TB) in a moderate TB incidence setting.MethodsThe participants were HCWs who had undergone serial LTBI screening between June 2013 and June 2018. IGRA-positive HCWs underwent examinations that included low-dose computed tomography (LDCT) and TB culture, if necessary. Applying the borderline zone (0.2-ResultsThrough the follow-up of 477 HCWs, 441 (92.5%) invariant, 30 (6.3%) conversion, 2 (0.4%) reversion and 5 (1.0%) indeterminate results were observed with the manufacturer's cutoff. Applying the borderline zone, 419 (87.8%) invariant, 22 (4.6%) conversion, 1 (0.2%) reversion and 36 (7.5%) decision pending, including 5 (1.0%) indeterminate results, were observed. At the time of screening, five TB cases were identified. Chest X-ray (CXR) identified one TB case, and LDCT identified four additional TB cases. After one year, two TB cases were diagnosed, and their screening QFT-GIT results were definite positive and borderline negative. In the Cochran-Armitage trend test, the greater the maximum difference in the QFT-GIT grade with the borderline zone was, the higher the probability of developing TB (P-value ConclusionThe application of the borderline zone lowered the conversion rate but increased the decision pending rate. Introducing the borderline zone requires a careful approach, and a thorough examination needs to be performed to rule out TB in converters. HCWs with borderline QFT-GIT results also need close observation.

Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.

Chronic rhinosinusitis (CRS) shows heterogeneous immunologic features. Western studies revealed that CRS without nasal polyps (CRSsNP) showed a predominantly type 1 immune response and CRS with nasal polyps (CRSwNP) was characterized by type 2 immune response; however, the detailed immunologic profile of CRSsNP in Asian patients has not been thoroughly investigated. Therefore, we investigated the inflammatory endotypes of CRSsNP in Asian patients. Patients with CRSsNP (N=57), patients with CRSwNP (N=13), and a control group (N=10), who underwent endoscopic sinus surgery, were enrolled; uncinate process (UP) tissues were harvested from all patients. Homogenates were prepared from the UP of each group, and immunologic profiles were analyzed, including major cytokines (32 inflammatory mediators). When comparing the UPs between groups, CRSsNP patients showed higher levels of Th2 cytokines (IL-4 and IL-13), eosinophilic chemokines (CCL-11 and CCL-24), ECP, and total IgE expression than control subjects. In addition, several neutrophilic markers (IL-1α, IL-6, IL-8, CXCL-1, CXCL-2, and MPO), IL-17A, IL-22, and TNF-α were dominant in CRSsNP patients. Among these inflammatory mediators, IL-17A showed higher expression levels in CRSsNP patients than in the control group and CRSwNP patients. However, IFN-γ expression was not significantly elevated in CRSsNP patients. The levels of neutrophil-associated cytokines were well correlated with each other; of which, CXCL2, IL-8, and MMP-9/TIMP-1 levels were significantly correlated with disease extent (r=0.338, r=0.317, and r=0.424, respectively). However, the levels of eosinophil-associated cytokines showed little correlation with each other and were not correlated with disease extent. Our study revealed that Asian CRSsNP patients showed a mixed (types 2 and 17) immune response, but neutrophil-related markers were dominant and associated with disease extent. Knowledge of this immunologic feature may help clinicians make better individual treatment decisions for Asian CRSsNP patients.

Background: Several T-cell response assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are available; however, their comparability and correlations with antibody responses remain unclear. We compared four SARS-CoV-2 T-cell response assays and two anti-SARS-CoV-2 spike antibody assays. Methods: We enrolled 89 participants who had received a booster dose of the BNT162b2 vaccine after two doses of the ChAdOx1 or BNT162b2 vaccine. Fifty-six participants without breakthrough infection (BI) (ChAdOx1/BNT162b2 group: N=27; BNT162b2 group: N=29) and 33 with BI were included. We evaluated two whole-blood interferon-gamma release assays (IGRAs) (QuantiFERON and Euroimmun), T-SPOT.COVID, an in-house enzyme- linked immunospot (ELISPOT) assay (targeting the spike and nucleocapsid peptides of wild-type and Omicron SARS-CoV-2), Abbott IgG II Quant, and Elecsys Anti-S, using Mann-Whitney U, Wilcoxon signed-rank, and Spearman's correlation tests. Results: The correlations between the IGRAs and between the ELISPOT assays (ρ=0.60- 0.70) were stronger than those between the IGRAs and ELISPOT assays (ρ=0.33-0.57). T-SPOT.COVID showed a strong correlation with Omicron ELISPOT (ρ=0.70). The anti-spike antibody assays showed moderate correlations with T-SPOT.COVID, Euroimmun IGRA, and ELISPOT (ρ=0.43-0.62). Correlations tended to be higher in the BI than in the noninfected group, indicating that infection induces a stronger immune response. Conclusions: T-cell response assays show moderate to strong correlations, particularly when using the same platform. T-SPOT.COVID exhibits potential for estimating immune responses to the Omicron variant. To accurately define SARS-CoV-2 immune status, both T-cell and B-cell response measurements are necessary. [ABSTRACT FROM AUTHOR]