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Abstract This study aimed to identify plasma proteins that could serve as potential biomarkers for microbial invasion of the amniotic cavity (MIAC) or intra-amniotic inflammation (IAI) in women with preterm labor (PTL). A retrospective cohort comprised singleton pregnant women with PTL (24–34 weeks) who underwent amniocentesis. Pooled plasma samples were analyzed by label-free liquid chromatography-tandem mass spectrometry for proteome profiling in a nested case–control study (concomitant MIAC/IAI cases vs. non-MIAC/IAI controls [n = 10 per group]). Eight target proteins associated with MIAC/IAI were further verified by immunoassays in a large cohort (n = 230). Shotgun proteomic analysis revealed 133 differentially expressed proteins (fold change > 1.5, P

The pores in lotus-type porous copper are formed due to the difference in hydrogen solubility between the liquid and solid phases of copper. In a pressurized hydrogen atmosphere, hydrogen gas is released at the gas release and crystallization temperature, which is the melting point of copper. This study systematically analyzes the effects of process parameters, including hydrogen ratio, total pressure, and continuous casting speed, on the pore structure of lotus-type porous copper, with the aim of identifying the most critical process parameters for controlling pore diameter and density. Within the hydrogen ratio up to 50%, it was observed that as the hydrogen ratio increases, the pores tend to increase in porosity, and the pore diameter increases. As the hydrogen ratio increased from 25% to 50%, the pore diameter increased from 300 μm to 400 μm, while the pore density decreased from 3.3 N·mm−2 to 2.8 N·mm−2. As the total pressure increased, the pore diameter tended to decrease, and the pore density increased. Specifically, when the total pressure increased from 0.2 MPa to 0.4 MPa, the pore diameter decreased from 1100 μm to 400 μm, while the pore density increased significantly from 0.5 N·mm−2 to 2.8 N·mm−2. In addition, as the continuous casting speed increased, 30 to 90 mm·min−1, the pore diameter decreased from 850 μm to 400 μm, and the pore density increased from 0.7 N·mm−2 to 2.8. N·mm−2. Specifically, the increase in total pressure led to a decrease in Gibbs free energy and a reduction in the critical pore nucleation radius, which promoted pore formation and resulted in the creation of more, smaller pores. These results suggest that total pressure is the primary factor influencing both pore diameter and density in lotus-type porous copper.

Abstract Clinical guidelines recommend several risk factors to identify women in early pregnancy at high risk of developing pregnancy-associated hypertension. However, these variables result in low predictive accuracy. Here, we developed a prediction model for pregnancy-associated hypertension using graph-based semi-supervised learning. This is a secondary analysis of a prospective study of healthy pregnant women. To develop the prediction model, we compared the prediction performances across five machine learning methods (semi-supervised learning with both labeled and unlabeled data, semi-supervised learning with labeled data only, logistic regression, support vector machine, and random forest) using three different variable sets: [a] variables from clinical guidelines, [b] selected important variables from the feature selection, and [c] all routine variables. Additionally, the proposed prediction model was compared with placental growth factor, a predictive biomarker for pregnancy-associated hypertension. The study population consisted of 1404 women, including 1347 women with complete follow-up (labeled data) and 57 women with incomplete follow-up (unlabeled data). Among the 1347 with complete follow-up, 2.4% (33/1347) developed pregnancy-associated HTN. Graph-based semi-supervised learning using top 11 variables achieved the best average prediction performance (mean area under the curve (AUC) of 0.89 in training set and 0.81 in test set), with higher sensitivity (72.7% vs 45.5% in test set) and similar specificity (80.0% vs 80.5% in test set) compared to risk factors from clinical guidelines. In addition, our proposed model with graph-based SSL had a higher performance than that of placental growth factor for total study population (AUC, 0.71 vs. 0.80, p

Abstract Background There have been reports of increases in the incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) in several countries, but no studies have analyzed claims data using laboratory tests. This study aimed to estimate the nationwide epidemiology and medical treatments of NTM-PD according to laboratory tests run in Korea. Methods Using claims data from the Health Insurance Review and Assessment Service, we analyzed patients with nontuberculous mycobacterium (ICD-10: A31) who were diagnosed from Jan 2007 to Jun 2019. The incidence and prevalence of NTM-PD and whether related laboratory tests were performed were analyzed. Diagnostic code-based NTM-PD patients were defined as patients who had NTM as a diagnosis on at least 2 occasions within 180 days. Clinically refined NTM-PD patients were defined as those excluding hospital-diagnosed patients with acid-fast bacilli (AFB) culture rates less than 5%. Laboratory tests included AFB smears, AFB culture, NTM identification, and drug susceptibility tests (DSTs). Results A total of 60,071 diagnostic code-based NTM-PD patients were evaluated. Clinically refined NTM-PD included 45,321 patients, excluding 14,750 (24.6%) patients diagnosed in hospitals with low AFB culture rates. The annual incidence per 100,000 population increased from 2.9 cases in 2008 to 12.3 cases in 2018. The annual prevalence per 100,000 population increased from 5.3 cases in 2008 to 41.7 cases in 2018. After removing outliers according to the AFB culture rate, a significant decrease in incidence was observed in women younger than 50 years. Among patients with clinically refined NTM-PD, the test rates for AFB culture, NTM identification, and DST were 84.3%, 59.1%, and 40.4%, respectively. From the outpatient clinic, 17,977 (39.7%) patients were prescribed drugs related to NTM treatment, with a median number of prescriptions of 7 (interquartile range (IQR) 3–11) and a median duration from the diagnosis to end of treatment of 330 (IQR 118–578) days. Conclusions Although the incidence and prevalence of NTM-PD are on the rise, the recent surge in women 50 years of age is overestimated in patients not adequately tested. In claim-based studies, there may be limitations in estimating the epidemiological data with only the diagnostic codes.

Background/Aims To develop an early prediction model for gestational diabetes mellitus (GDM) using machine learning and to evaluate whether the inclusion of nonalcoholic fatty liver disease (NAFLD)-associated variables increases the performance of model. Methods This prospective cohort study evaluated pregnant women for NAFLD using ultrasound at 10–14 weeks and screened them for GDM at 24–28 weeks of gestation. The clinical variables before 14 weeks were used to develop prediction models for GDM (setting 1, conventional risk factors; setting 2, addition of new risk factors in recent guidelines; setting 3, addition of routine clinical variables; setting 4, addition of NALFD-associated variables, including the presence of NAFLD and laboratory results; and setting 5, top 11 variables identified from a stepwise variable selection method). The predictive models were constructed using machine learning methods, including logistic regression, random forest, support vector machine, and deep neural networks. Results Among 1,443 women, 86 (6.0%) were diagnosed with GDM. The highest performing prediction model among settings 1–4 was setting 4, which included both clinical and NAFLD-associated variables (area under the receiver operating characteristic curve [AUC] 0.563–0.697 in settings 1–3 vs. 0.740–0.781 in setting 4). Setting 5, with top 11 variables (which included NAFLD and hepatic steatosis index), showed similar predictive power to setting 4 (AUC 0.719–0.819 in setting 5, P=not significant between settings 4 and 5). Conclusions We developed an early prediction model for GDM using machine learning. The inclusion of NAFLD-associated variables significantly improved the performance of GDM prediction. (ClinicalTrials.gov Identifier: NCT02276144)

Abstract We evaluated the relationship between maternal cholesterol levels and its biologically active precursors and metabolites in the first trimester and subsequent risk for small-for-gestational-age birthweight (SGA). This is a secondary analysis of a prospective cohort study which enrolled healthy singleton pregnancies (n = 1337). Maternal fasting blood was taken in the first trimester and followed up till delivery. The lipid parameters were compared between women who delivered SGA neonates (SGA-group, birthweight

Background/Aims: Ulcerative colitis (UC) is an inflammatory bowel disease for which new serological markers are required. The purpose of this study was to assess the role of the mucosa-associated epithelial chemokine CCL28 in UC. Methods: The study included 50 patients; of these, 25 were patients with UC, and 25 were healthy controls. The levels of serum CCL28 were analyzed using enzyme-linked immunosorbent assay. CCL28 expression was analyzed by immunohistochemistry (IHC) in 15 representative colon tissues biopsied based on disease activity (UC patients with severe activity, five samples; UC patients with mild activity, five samples; healthy controls, five samples). Results: The serum CCL28 levels were remarkably higher (p

Background The definition of the high-risk group for gestational diabetes mellitus (GDM) defined by the American College of Obstetricians and Gynecologists was changed from the criteria composed of five historic/demographic factors (old criteria) to the criteria consisting of 11 factors (new criteria) in 2017. To compare the predictive performances between these two sets of criteria. Methods This is a secondary analysis of a large prospective cohort study of non-diabetic Korean women with singleton pregnancies designed to examine the risk of GDM in women with nonalcoholic fatty liver disease. Maternal fasting blood was taken at 10 to 14 weeks of gestation and measured for glucose and lipid parameters. GDM was diagnosed by the two-step approach. Results Among 820 women, 42 (5.1%) were diagnosed with GDM. Using the old criteria, 29.8% (n=244) of women would have been identified as high risk versus 16.0% (n=131) using the new criteria. Of the 42 women who developed GDM, 45.2% (n=19) would have been mislabeled as not high risk by the old criteria versus 50.0% (n=21) using the new criteria (1-sensitivity, 45.2% vs. 50.0%, P>0.05). Among the 778 patients who did not develop GDM, 28.4% (n=221) would have been identified as high risk using the old criteria versus 14.1% (n=110) using the new criteria (1-specificity, 28.4% vs. 14.1%, P

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.

Along with positive SARS-CoV-2 RNA in nasopharyngeal swabs, viral RNA was detectable at high concentration for >3 weeks in fecal samples from 12 mildly symptomatic and asymptomatic children with COVID-19 in Seoul, South Korea. Saliva also tested positive during the early phase of infection. If proven infectious, feces and saliva could serve as transmission sources.

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)

Rapid antigen tests (RATs) for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are widely used in the Coronavirus disease 2019 (COVID-19) pandemic caused by diverse variants. Information on the real-world performance of RATs for variants is urgently needed for decision makers. Systematic searches of the available literature and updates were conducted in PubMed, Ovid-MEDLINE, Ovid-EMBASE, CENTRAL, and KMBASE for articles evaluating the accuracy of instrument-free RATs for variants up until 14 March 2022. A bivariate random effects model was utilized to calculate pooled diagnostic values in comparison with real-time reverse transcription-polymerase chain reaction as the reference test. A total of 7562 samples from six studies were available for the meta-analysis. The overall pooled sensitivity and specificity of RATs for variants were 69.7% (95% confidence interval [CI] = 62.5% to 76.1%) and 100.0% (95% CI = 98.8% to 100.0%), respectively. When an additional 2179 samples from seven studies reporting sensitivities only were assessed, the pooled sensitivity dropped to 50.0% (95% CI = 44.0% to 55.0%). These findings suggest reassessment and monitoring of the diagnostic utility of RATs for variants, especially for the sensitivity aspect, to facilitate appropriate diagnosis and management of COVID-19 patients.

Objective We sought to identify plasma biomarkers associated with spontaneous preterm birth (SPTB, delivery within 21 days of sampling) in women with preterm labor (PTL) without intra-amniotic infection/inflammation (IAI) using label-free quantitative proteomic analysis, as well as to elucidate specific protein pathways involved in these cases. Methods This was a retrospective cohort study comprising 104 singleton pregnant women with PTL (24–32 weeks) who underwent amniocentesis and demonstrated no evidence of IAI. Analysis of pooled plasma samples collected from SPTB cases and term birth (TB) controls (n = 10 for each group) was performed using label-free quantitative mass spectrometry for proteome profiling in a nested case-control study design. Eight candidate proteins of interest were validated by ELISA-based assay and a clot-based assay in the total cohort. Results Ninety-one proteins were differentially expressed (P < 0.05) in plasma samples obtained from SPTB cases, of which 53 (58.2%) were upregulated and 38 (41.8%) were downregulated when compared to TD controls. A validation study confirmed that plasma from women who delivered spontaneously within 21 days of sampling contained significantly higher levels of coagulation factor Ⅴ and lower levels of S100 calcium binding protein A9 (S100A9), especially the former which was independent of baseline variables. The top-ranked pathways related to the 91 differentially expressed proteins were liver-X-receptor/retinoid X receptor (RXR) activation, acute phase response signaling, farnesoid X receptor/RXR activation, coagulation system, and complement system. Conclusions Proteomic analyses in this study identified potential novel biomarkers (i.e., coagulation factor V and S100A9) and potential protein pathways in plasma associated with SPTB in the absence of IAI in women with PTL. The present findings provide novel insights into the molecular pathogenesis and therapeutic targets specific for idiopathic SPTB.

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.

ObjectiveWe sought to identify novel biomarkers in the amniotic fluid (AF) related to imminent spontaneous preterm delivery (SPTD) (≤ 14 days after sampling) in women with early preterm premature rupture of membranes (PPROM), using a protein microarray.MethodThis was a retrospective cohort study of a total of 88 singleton pregnant women with PPROM (23+0 to 30+6 weeks) who underwent amniocentesis. A nested case-control study for biomarker discovery was conducted using pooled AF samples from controls (non-imminent delivery, n = 15) and cases (imminent SPTD, n = 15), which were analyzed using an antibody microarray. Quantitative validation of four candidate proteins was performed, using ELISA, in the total cohort (n = 88). IL-8, MMP-9, and Fas levels were additionally measured for the comparison and to examine association of SPTD with the etiologic factors of PPROM.ResultsOf all the proteins studied in the protein microarray, four showed significant intergroup differences. Analyses of the total cohort by ELISA confirmed the significantly elevated concentrations of AF lipocalin-2, MMP-9, and S100 A8/A9, but not of endostatin and Fas, in women who delivered within 14 days of sampling. For inflammatory proteins showing a significant association, the odds of SPTD within 14 days increased significantly with an increase in baseline AF levels of the proteins (P for trend ConclusionsWe identified several potential novel biomarkers (i.e., lipocalin-2, MMP-9, and S100 A8/A9) related to SPTD within 14 days of sampling, all of which are inflammation-related molecules. Furthermore, the SPTD risk increased with increasing quartiles of each of these inflammatory proteins, especially the 3rd and 4th quartile of each protein. The present findings may highlight the importance of inflammatory mechanisms and the degree of activated inflammatory response in developing SPTD in early PPROM.

ABSTRACT Objective: To investigate the safety and efficacy of allogeneic platelet-rich plasma (PRP) in rotator cuff repair . Methods: Seventeen patients with a full-thickness rotator cuff tear were included. Ten patients underwent arthroscopic rotator cuff repair with allogeneic, and seven patients with autologous PRP. Three PRP gels in a volume 3 ml each were applied between the torn end and the greater tuberosity. Clinical outcomes were assessed preoperatively and at a minimum of 2 years after surgery. Structural outcomes were evaluated with the presence of retear and the change of the cross-sectional area (ACT) of the supraspinatus . Results: Allogeneic PRP did not cause any adverse events during the follow-up period. There was no significant difference in the clinical outcome measures between the two groups (all p > 0.05). The retear rate was 33.3% and 25.0% in the allogeneic group and autologous group, respectively (p = 0.764). The change between the one-year postoperative and immediately postoperative ACT was not also significantly different between the two groups (p = 0.373) . Conclusion: Allogeneic PRP in arthroscopic rotator cuff did not cause any local or general complications and that has the efficacy comparable to autologous PRP with respect to the clinical and structural outcomes. Level of Evidence III, Retrospective Comparative Study.

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.

[This corrects the article DOI: 10.1371/journal.pone.0221400.].

ObjectiveNonalcoholic fatty liver disease (NAFLD) is a well-recognized hepatic manifestation of metabolic disease in adults and has been associated with the development of gestational diabetes (GDM). Hepatic insulin resistance can result in increased release of glucose (from gluconeogenesis) and free fatty acids (due to enhanced lipolysis), which can lead in turn to fetal overgrowth. However, the relationship between maternal metabolic factors (such as circulating levels of triglycerides, free fatty acids [FFA], or adipokines) and excessive fetal birthweight in NAFLD has not been carefully examined. In this study, we evaluated the relationship between NAFLD and the subsequent risk of large-for-gestational-age (LGA) birthweight.MethodSingleton nondiabetic pregnant women were evaluated for the presence of fatty liver at 10-14 weeks of gestation by abdominal ultrasound. The degree of fatty liver was classified as Grade 0-3 steatosis. At the time of liver ultrasound, maternal blood was taken after fasting and measured for adiponectin and FFA. LGA was defined as birthweight >90th percentile for gestational age.ResultsA total of 623 women were included in the analysis. The frequency of LGA was 10.9% (68/623), and the frequency of NAFLD was 18.9%. The risk of LGA increased significantly in patients with Grade 2-3 steatosis in the first trimester. The relationship between Grade 2-3 steatosis and LGA remained significant after adjustment for maternal age, pre-pregnancy BMI, GDM, and maternal serum triglyceride levels. The concentration of maternal blood adiponectin at 10-14 weeks was significantly lower in cases with LGA than non-LGA, but the maternal blood FFA concentrations were not different between the groups.ConclusionThe presence of Grade 2-3 steatosis on ultrasound in early pregnancy was associated with the increased risk of delivering an LGA infant, even after adjustment for multiple confounding factors including GDM. Adiponectin may be the linking biomarker between NAFLD and LGA.

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]

Chronic granulomatous disease (CGD) is a rare inherited disorder caused by defective nicotinamide adenine dinucleotide phosphate oxidase enzyme and characterized by recurrent bacterial and fungal infections. Although liver abscess is a common manifestation of CGD, its management in CGD patients is not well-defined. In addition, the generalized guidelines for treating liver abscesses do not necessarily apply to CGD patients. Corticosteroids are commonly used to control granulomatous complications, such as inflammatory gastrointestinal and genitourinary lesions, in patients with CGD, Corticosteroids have also been used in combination with antimicrobials to treat refractory infections in patients with CGD. Because corticosteroids are capable of suppressing symptomatic inflammation, all potential infections must be adequately controlled prior to corticosteroid initiation. We report 3 typical CGD cases with liver abscesses refractory to conventional treatments that were successfully treated with the concomitant use of corticosteroid and antimicrobials. It remains unclear whether corticosteroid therapy is required for liver abscesses in CGD refractory to conventional treatments. However, based on our observations, use of corticosteroids in combination with optimal antimicrobials should be considered for refractory liver abscesses in CGD.

PurposeThis study investigated the long-term clinical outcomes of patients with p22phox-deficient chronic granulomatous disease (CGD) on Jeju Island and retrospectively evaluated the effects of interferon-gamma (IFN-γ) prophylaxis.MethodsThe medical records of 15 patients with CGD were retrospectively reviewed. The efficacy of IFN-γ prophylaxis was evaluated by comparing the frequency of severe infections before and after starting continuous prophylaxis with IFN-γ.ResultsAt the time of the analysis, 14 patients were alive, with a median age of 14.3 years. The diagnosis of CGD was made at a median age of 2.4 years, and the median age at onset of severe infection was 0.3 years. Thirteen of the 15 patients had their first severe infection within the first year of life. The overall incidence of severe infection was 1.36 infections per patient-year; pneumonia, suppurative lymphadenitis, and skin and subcutaneous abscesses were the most common infections. Aspergillus species were the most frequently isolated microorganisms, present in 15.8% of isolates. IFN-γ did not significantly change the rate of severe infection. The survival rate for patients after 2 years of age was 93%; there was a prolonged survival plateau beyond the age of 2.ConclusionCompared with cases of X-linked CGD reported in other studies, patients with CGD on Jeju Island did not show obviously different clinical manifestations, but they had a significantly higher survival rate. Further studies with a substantially longer period of observation, and with more patients under intensive surveillance are necessary to elucidate the prophylactic efficiency of IFN-γ.

A recent study has suggested that fibroblasts can be converted into mouse-induced neural stem cells (miNSCs) through the expression of defined factors. However, successful generation of human iNSCs (hiNSCs) has proven challenging to achieve. Here, using microRNA (miRNA) expression profile analyses, we showed that let-7 microRNA has critical roles for the formation of PAX6/NESTIN-positive colonies from human adult fibroblasts and the proliferation and self-renewal of hiNSCs. HMGA2, a let-7-targeting gene, enables induction of hiNSCs that displayed morphological/molecular features and in vitro/in vivo differentiation potential similar to H9-derived NSCs. Interestingly, HMGA2 facilitated the efficient conversion of senescent somatic cells or blood CD34+ cells into hiNSCs through an interaction with SOX2, whereas other combinations or SOX2 alone showed a limited conversion ability. Taken together, these findings suggest that HMGA2/let-7 facilitates direct reprogramming toward hiNSCs in minimal conditions and maintains hiNSC self-renewal, providing a strategy for the clinical treatment of neurological diseases.

Cord blood units (CBUs) for transplantation should be free of communicable disease and must contain a specific amount of total nucleated cells and CD34 + cells. Although posttransplantation cytomegalovirus (CMV) infections are from latent infection in patients, ensuring CMV-free CBUs by performing CMV-specific IgM and nucleic acid amplification testing (NAT) is one of the mandatory procedures for the safety of CBUs. However, the exclusion policies (based on these test results) vary among nations and institutions. We tested 28,000 processed CBUs between May 2006 and June 2014. The cord blood leukocytes from CMV IgM-positive samples were then subjected to NAT. The total nucleated cell and CD34 + cell counts were measured for each CBU, and the results were compared to the CMV IgM and IgG results. The seroprevalence of CMV among pregnant women was 98.1% (18,459/18,818) for IgG and 1.7% (441/25,293) for IgM. The concentration and the total number of CD34 + cells were significantly higher in CBUs from IgM-negative mothers compared to those from IgM-positive mothers (72.4/μl vs. 57.2/μl, respectively, p < 0.0001; 1.45 × 10 6 /unit vs. 1.15 × 10 6 /unit, respectively, p < 0.0001). Among CBUs with positive CMV IgM in their mothers' plasma or cord blood plasma, only 0.58% of the samples (3/517) had a positive NAT. The number of excluded CBUs from inventory due to positive CMV IgM in the cord blood was 54 of 18,326 (0.3%). For inventory purposes, it is appropriate to remove CBUs with positive cord blood CMV IgM findings irrespective of the NAT status as well as positive maternal CMV IgM in South Korea.