Nitro-Enabled Atroposelective Dynamic Kinetic Resolution of 2-Arylindoles by Phase-Transfer Catalysis.

This study presents the atroposelective alkylation of 2-arylindoles catalyzed by a substituted cinchonium salt as a phase-transfer catalyst. Under the optimized reaction conditions, various substrates are employed to yield products with high enantioselectivity. The presence of an ortho-nitro group at the aromatic ring is essential for high atroposelectivity, because it facilitates favorable interactions between the catalyst and substrate. The origin of the enantioselectivity reveals favorable π-π interactions for both enantiomers and unfavorable steric strains for undesired enantiomers.

All-round catalytic and atroposelective strategy via dynamic kinetic resolution for N-/2-/3-arylindoles.

As the complexity of organic molecules utilized by mankind increases, the phenomenon of atropisomerism is more frequently encountered. While a variety of well-established methods enable the control of a stereogenic center, a catalytic method for controlling a stereogenic axis in one substrate is typically unavailable for controlling axial chirality in other substrates with a similar structure. Herein, we report o-amidobiaryl as a flexible platform for chiral phosphoric acid-catalyzed atroposelective dynamic kinetic resolution. To demonstrate our strategy, three distinct types of arylindoles were utilized and reacted intermolecularly with ketomalonate in the presence of chiral phosphoric acid. An investigation of 46 substrates having an aromatic ring in different positions yields the desired products with excellent enantioselectivities. Computational investigation into the origin of enantioselectivity highlights the importance of the NH group. Given the biological significance of indoles, antiproliferative effects have been investigated; our scaffold exhibits good efficacy in this regard.

Characterization of virus-mediated autoimmunity and the consequences for pathological process in patients with systemic lupus erythematosus.

INTRODUCTION/OBJECTIVES: This study aimed to identify differentially expressed genes (DEGs) of systemic lupus erythematosus (SLE) using gene expression-based computational methodologies to analyze disease-immune interactions, which affect the development and progression of SLE. METHOD: Twenty-six patients with SLE and 46 healthy controls were selected from the Gene Expression Omnibus (GEO) database. The significantly enriched immune and virus-related gene lists were computed and visualized by using the DEGs from the gene set enrichment analysis (GSEA). Quantification of 38 immune cells was performed in determining the impact of immune cells on the virus mediated immunity in SLE by using ImmQuant algorithm. RESULTS: Thirty-nine upregulated and 57 downregulated were identified in SLE patient compared to the healthy controls. Upregulated genes were significantly implicated in Gene Ontology gene sets as cytokine mediated signaling, secretion, and exocytosis in immune response pathways in 26 female SLE patients. In addition, these genes were enriched in hepatitis C, influenza A, measles, Epstein-Barr virus, and herpes simplex virus 1 infection in Kyoto Encyclopedia of Genes and Genomes pathways. Especially, FCGR1A, IRF7, OAS2, CAMP, MX1, OAS3, OAS1, DEFA3, ISG15, and RSAD2 were involved in virus mediated SLE mechanism, and the expression for OAS1, OAS2, and IRF7 was closely associated with the quantities of colony forming unit-monocyte and colony forming unit-granulocyte. CONCLUSIONS: Identifying virus-mediated SLE genes and quantifies of immune cells were used to understand the pathological process and perform early diagnosis of female SLE, and will lead to clinical tools for treating SLE in patients. Key Points • Using gene expression-based computational methodologies, the 57 immune and viral genes were significantly upregulated in 26 SLE patients. • The identified three key  viral genes such as OAS1, OAS2, and IF7 were closely associated with colony-forming unit-monocytes and colony-forming unit-granulocytes, which affect the virus mediated immunity in SLE. • The viral genes and quantifies of immune cells are useful in understanding pathogenesis of SLE, and this will provide clinical strategies of potential treatment choices in SLE patients.

The prevalence of multiple chronic conditions and medical burden in asthma patients.

BACKGROUND: The prevalence of multiple chronic conditions (MCC), defined as several coexisting chronic conditions, has increased with the aging of society. MCC is associated with poor outcomes, but most comorbid diseases in asthma patients have been evaluated as asthma-associated diseases. We investigated the morbidity of coexisting chronic diseases in asthma patients and their medical burdens. METHODS: We analyzed data from the National Health Insurance Service-National Sample Cohort for 2002-2013. We defined MCC with asthma as a group of one or more chronic diseases in addition to asthma. We analyzed 20 chronic conditions, including asthma. Age was categorized into groups 1-5 (< 10, 10-29, 30-44, 45-64, and ≥ 65 years, respectively). The frequency of medical system use and associated costs were analyzed to determine the asthma-related medical burden in patients with MCC. RESULTS: The prevalence of asthma was 13.01%, and the prevalence of MCC in asthmatic patients was 36.55%. The prevalence of MCC with asthma was higher in females than males and increased with age. The significant comorbidities were hypertension, dyslipidemia, arthritis, and diabetes. Dyslipidemia, arthritis, depression, and osteoporosis were more common in females than males. Hypertension, diabetes, COPD, coronary artery disease, cancer, and hepatitis were more prevalent in males than females. According to age, the most prevalent chronic condition in groups 1 and 2 was depression, dyslipidemia in group 3, and hypertension in groups 4 and 5. Older age, low income, and severe disability were independent risk factors for MCC in patients with asthma. The frequency of asthma-related medical system use and asthma-associated costs increased with increasing numbers of coexisting chronic diseases. CONCLUSION: Comorbid chronic diseases in asthma patients differed according to age and sex. The asthma-related-medical burdens were highest in patients with five or more chronic conditions and groups 1 and 5.

The High Prevalence of Sarcopenia in Rheumatoid Arthritis in the Korean Population: A Nationwide Cross-Sectional Study.

Rheumatoid arthritis (RA) includes musculoskeletal symptoms that lead to disuse atrophy of muscles and changes in body composition. Musculoskeletal symptoms and loss of physical function may be associated with sarcopenia, which is characterized by muscle loss. This study aimed to investigate the prevalence of sarcopenia and its association with RA in a Korean population. We analyzed nationwide data from the Korea National Health and Nutrition Examination Survey of 7389 men and 9798 women. Binomial logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for sarcopenia prevalence in participants with RA. The prevalence of sarcopenia was 23.0% in men, 25.0% in women, 61.5% in men with RA, 32.3% in women with RA, 22.8% in men without RA, and 24.9% in women without RA. After adjusting for potential confounding variables, the prevalence of sarcopenia was higher in men with RA than in men without RA (OR, 3.11; 95% CI, 1.29-7.46), but this difference was not observed in women. In subgroup analysis which was stratified by age (age under 40, age between 40 and 59, age over 60), the OR for sarcopenia was higher in men with age over 60 years (OR, 4.12; 95% CI, 1.48-11.44) and women with age between 40 and 59 (OR, 2.29; 95% CI, 1.05-5.00). The prevalence of sarcopenia was higher in Korean men with RA and women with RA in middle age, suggesting the management of muscle loss will be needed, especially in Koreans with RA.

Synthesis and biological evaluation of atropisomeric tetrahydroisoquinolines overcoming docetaxel resistance in triple-negative human breast cancer cells.

Herein, atropisomeric 8-aryltetrahydroisoquinolines have been synthesized and biologically evaluated. Based on our structure-activity relationship study, a highly bioactive racemic compound has been produced, and it exhibited high antiproliferative activities against various cancer cell lines, including docetaxel-resistant breast cancer cell lines. Each enantiomer can be synthesized in an enantioselective manner by employing the chiral phosphoric acid-catalyzed atroposelective Pictet-Spengler cyclization. An axially (R)-configured enantiomer showed a higher biological activity compared with the axially (S)-configured enantiomer. Further biological studies suggested that the (R)-enantiomer overcomes docetaxel resistance via the downregulation of signal transducer and activator of transcription 3 activation and consequently induces cellular apoptosis in docetaxel-resistant triple-negative breast cancer cell lines.

Organocatalytic Atroposelective Synthesis of Isoquinolines via Dynamic Kinetic Resolution.

Herein, a highly enantioselective Pictet-Spengler reaction for the synthesis of axially chiral tetrahydroisoquinolines via dynamic kinetic resolution is described. Chiral phosphoric acids catalyze cyclization to yield single regioisomeric isoquinolines with excellent enantioselectivities around the C-C bond up to 99% ee. The current protocol is effective for a wide range of substrates, and the observed enantiodivergence depends on the substituents on the catalysts.

Genomic and transcriptomic analyses reveal a tandem amplification unit of 11 genes and mutations in mismatch repair genes in methotrexate-resistant HT-29 cells.

DHFR gene amplification is commonly present in methotrexate (MTX)-resistant colon cancer cells and acute lymphoblastic leukemia. In this study, we proposed an integrative framework to characterize the amplified region by using a combination of single-molecule real-time sequencing, next-generation optical mapping, and chromosome conformation capture (Hi-C). We identified an amplification unit spanning 11 genes, from the DHFR gene to the ATP6AP1L gene position, with high adjusted interaction frequencies on chromosome 5 (~2.2 Mbp) and a twenty-fold tandemly amplified region, and novel inversions at the start and end positions of the amplified region as well as frameshift insertions in most of the MSH and MLH genes were detected. These mutations might stimulate chromosomal breakage and cause the dysregulation of mismatch repair. Characterizing the tandem gene-amplified unit may be critical for identifying the mechanisms that trigger genomic rearrangements. These findings may provide new insight into the mechanisms underlying the amplification process and the evolution of drug resistance.

Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells.

BACKGROUND: The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs. METHODS: Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO2 laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry. RESULTS: The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis. CONCLUSIONS: These results indicate that shikimic acid is an effective agent for tissue regeneration.

A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder.

Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.

Screening for Mycobacterium tuberculosis Infection Using Beijing/K Strain-Specific Peptides in a School Outbreak Cohort.

Background: The Beijing strain of Mycobacterium tuberculosis (M. tb) has been most frequently isolated from TB patients in South Korea, and the hyper-virulent Beijing/K genotype is associated with TB outbreaks. To examine the diagnostic potential of Beijing/K-specific peptides, we performed IFN-γ release assays (IGRA) using a MTBK antigen tube containing Beijing/K MTBK_24800, ESAT-6, and CFP-10 peptides in a cohort studied during a school TB outbreak. Methods: A total of 758 contacts were investigated for M. tb infection, and 43 contacts with latent TB infection (LTBI) and 25 active TB patients were enrolled based on serial screening with QuantiFERON-TB Gold In-Tube tests followed by clinical examinations. Blood collected in MTBK antigen tubes was utilized for IGRA and multiplex cytokine bead arrays. Immune responses were retested in 24 patients after TB treatment, and disease progression was investigated in subjects with LTBI. Results: Total proportions of active disease and LTBI during the outbreak were 3.7% (28/758) and 9.2% (70/758), respectively. All clinical isolates had a Beijing/K M. tb genotype. IFN-γ responses to the MTBK antigen identified M. tb infection and distinguished between active disease and LTBI. After anti-TB treatment, IFN-γ responses to the MTBK antigen were significantly reduced, and strong TNF-α responses at diagnosis were dramatically decreased. Conclusions: MTBK antigen-specific IFN-γ has diagnostic potential for differentiating M. tb infection from healthy controls, and between active TB and LTBI as well. In addition, TNF-α is a promising marker for monitoring therapeutic responses. These data provide informative readouts for TB diagnostics and vaccine studies in regions where the Beijing/K strain is endemic.

Integrative Genomic and Transcriptomic Analyses of Tumor Suppressor Genes and Their Role on Tumor Microenvironment and Immunity in Lung Squamous Cell Carcinoma.

Non-small-cell lung cancers (NSCLCs) are largely classified into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), which have different therapeutic options according to its molecular profiles and immune checkpoint expression, especially PD-L1, which is a suppressive factor in the tumor microenvironment. The tumor microenvironment can be altered by the genomic mutations on specific innate immune genes as well as tumor suppressor genes, so it is essential to comprehend the association between tumor microenvironment and tumor suppressor genes to discover the promising immunotherapeutic strategy to overcome the resistance of immune check point blockade. In this study, we aimed to analyze how the somatic mutations in tumor suppressor genes affect the tumor immune microenvironment through a comprehensive analysis of mutational profiling on the representative tumor suppressor genes (TP53, CDKN2A, PTEN, RB1, BRCA1, BRCA2) and immune gene expression in The Cancer Genome Atlas (TCGA) 155 lung squamous cell carcinoma (LUSC) and 196 lung adenocarcinoma (LUAD) samples. Several microenvironmental factors, such as the infiltrating immune and stromal cells, were suppressed by the mutated tumor suppressor genes in LUSC, unlike in the LUAD samples. In particular, infiltrating immune cells such as macrophage, neutrophil, and dendritic cells were significantly reduced in tumors with mutated tumor suppressor genes' group. In addition, the gene expressions for interleukin production and lymphocyte differentiation and PGC, C7, HGF, PLA2G2A, IL1RL1, CCR2, ALOX15B, CXCL11, FCN3 were significantly down-regulated, which were key immune genes for the cross-talk between LUSC microenvironment and tumor suppressors. Therefore, we generated evidence that TSG mutations in LUSC have an impact on tumor immune microenvironment, which suggests that TSG non-mutated patients will have the more inflamed tumors and are more likely to respond to immune checkpoint blockade therapy.

Catalytic and Enantioselective Control of the C-N Stereogenic Axis via the Pictet-Spengler Reaction.

An unprecedented example of a chiral phosphoric acid-catalyzed atroposelective Pictet-Spengler reaction of N-arylindoles is reported. Highly enantioenriched N-aryl-tetrahydro-ß-carbolines with C-N bond axial chirality are obtained via dynamic kinetic resolution. The hydrogen bond donor introduced on the bottom aromatic ring, forming a secondary interaction with the phosphoryl oxygen, is essential to achieving high enantioselectivity. A wide variety of substituents are tolerable with this transformation to provide up to 98 % ee. The application of electron-withdrawing group-substituted benzaldehydes enables the control of both axial and point stereogenicity. Biological evaluation of this new and unique scaffold shows promising antiproliferative activity and emphasizes the significance of atroposelective synthesis.

Diagnostic Potential of a PPE Protein Derived from Mycobacterium tuberculosis Beijing/K Strain.

PURPOSE: The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. MATERIALS AND METHODS: Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed. RESULTS: Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95-100%). CONCLUSION: Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.

The tumor immune microenvironmental analysis of 2,033 transcriptomes across 7 cancer types.

Understanding the tumor microenvironment is important to efficiently identify appropriate patients for immunotherapies in a variety of cancers. Here, we presented the tumor microenvironmental analysis of 2,033 cancer samples across 7 cancer types: colon adenocarcinoma, skin cutaneous melanoma, kidney renal papillary cell carcinoma, sarcoma, pancreatic adenocarcinoma, glioblastoma multiforme, and pheochromocytoma / paraganglioma from The Cancer Genome Atlas cohort. Unsupervised hierarchical clustering based on the gene expression profiles separated the cancer samples into two distinct clusters, and characterized those into immune-competent and immune-deficient subtypes using the estimated abundances of infiltrated immune and stromal cells. We demonstrated differential tumor microenvironmental characteristics of immune-competent subtypes across 7 cancer types, particularly immunosuppressive tumor microenvironment features in kidney renal papillary cell carcinoma with significant poorer survival rates and immune-supportive features in sarcoma and skin cutaneous melanoma. Additionally, differential genomic instability patterns between the subtypes were found across the cancer types, and discovered that immune-competent subtypes in most of cancer types had significantly higher immune checkpoint gene expressions. Overall, this study suggests that our subtyping approach based on transcriptomic data could contribute to precise prediction of immune checkpoint inhibitor responses in a wide range of cancer types.

Diverse anion exchange of pliable [X2@Pd3L4]4+ double cages: a molecular ruler for recognition of polyatomic anions.

Reaction of Pd(BF4)2 with L (L = bis(pyridin-3-yl-propyl)pyridine-3,5-dicarboxylate) in the 1 : 2 mole ratio gives rise to a spiro-type [PdL2]·(BF4)2·2C6H6·2CH3CN, and further self-assembly of [PdL2]·(BF4)2·2C6H6·2CH3CN with Pd(NO3)2 in the 2 : 1 mole ratio in Me2SO at 90 °C produces a uniquely pliable double cage of [(NO3)2(H2O)2@Pd3L4](BF4)4·6C3H7NO. Both the encapsulated NO3- and the outside BF4- anions are exchanged by X- to form [(X)2@Pd3L4](X')4 (X- = PF6-, ClO4-, and/or NO3-; X'- = BF4-, PF6-, ClO4-, and NO3-) with all-inclusive pure or mixed anions. The pliable and characteristic properties of the double cages were confirmed by anion exchange of the nestled or outside anions in the present study. This system can be used as a ruler for recognition of ubiquitous polyatomic anions.

Clinical outcomes of radial probe endobronchial ultrasound using a guide sheath for diagnosis of peripheral lung lesions in patients with pulmonary emphysema.

BACKGROUND: Generally, structural destruction of lung parenchyma, such as pulmonary emphysema, is considered to be related to the low diagnostic yields and high complication rates of lung biopsies of peripheral lung lesions. Currently, little is known about the clinical outcomes of using endobronchial ultrasound with a guide sheath (EBUS-GS) to diagnose peripheral lesions in patients with emphysema. METHODS: This retrospective study was performed to identify the clinical outcomes of EBUS-GS in patients with pulmonary emphysema. This study included 393 consecutive patients who received EBUS-GS between February 2017 and April 2018. The patients were classified according to the severity of their emphysema, and factors possibly contributing to a successful EBUS-GS procedure were evaluated. RESULTS: The overall diagnostic yield of EBUS-GS in patients with no or mild emphysema was significantly higher than in those with moderate or severe pulmonary emphysema (78% vs. 61%, P = 0.007). There were no procedure-related complications. The presence of a bronchus sign on CT (P <  0.001) and a "within the lesion" status on EBUS (P = 0.009) were independently associated with a successful EBUS-GS procedure. Although the diagnostic yield of EBUS-GS in patients with moderate-to-severe emphysema was relatively low, a bronchus sign and "within the lesion" status on EBUS were contributing factors for a successful EBUS-GS. CONCLUSIONS: EBUS-GS is a safe procedure with an acceptable diagnostic yield, even when performed in patients with pulmonary emphysema. The presence of a bronchus sign and "within the lesion" status on EBUS were predictors of a successful procedure.

PPE39 of the Mycobacterium tuberculosis strain Beijing/K induces Th1-cell polarization through dendritic cell maturation.

In a previous study, we have identified MTBK_24820, the complete protein form of PPE39 in the hypervirulent Mycobacterium tuberculosis (Mtb) strain Beijing/K by using comparative genomic analysis. PPE39 exhibited vaccine potential against Mtb challenge in a murine model. Thus, in this present study, we characterize PPE39-induced immunological features by investigating the interaction of PPE39 with dendritic cells (DCs). PPE39-treated DCs display reduced dextran uptake and enhanced MHC-I, MHC-II, CD80 and CD86 expression, indicating that this PPE protein induces phenotypic DC maturation. In addition, PPE39-treated DCs produce TNF-α, IL-6 and IL-12p70 to a similar and/or greater extent than lipopolysaccharide-treated DCs in a dose-dependent manner. The activating effect of PPE39 on DCs was mediated by TLR4 through downstream MAPK and NF-κB signaling pathways. Moreover, PPE39-treated DCs promoted naïve CD4+ T-cell proliferation accompanied by remarkable increases of IFN-γ and IL-2 secretion levels, and an increase in the Th1-related transcription factor T-bet but not in Th2-associated expression of GATA-3, suggesting that PPE39 induces Th1-type T-cell responses through DC activation. Collectively, the results indicate that the complete form of PPE39 is a so-far-unknown TLR4 agonist that induces Th1-cell biased immune responses by interacting with DCs.This article has an associated First Person interview with the first author of the paper.

Feasibility of low dose chest CT for virtual bronchoscopy navigation in a porcine model.

BACKGROUND: Virtual bronchoscopy navigation (VBN) is widely used for assistance in the histological examination of lung nodules. However, little is known about the optimal CT radiation dose for VBN. Therefore, we performed an animal study to evaluate the feasibility of low dose CT (LDCT) for VBN. METHODS: Ten pigs underwent standard dose CT (as a reference) and four different LDCT protocols: LDCT 1, 120 kVp, 15 mAs; LDCT 2, 120 kVp, 8 mAs; LDCT 3, 100 kVp, 7 mAs; and LDCT 4, 100 kVp, 4 mAs. As targets for the VBN, 10 mm virtual lesions were created in the central and peripheral bronchi. To assess the performance of the VBN, the navigation direction (direction of reconstructed pathways to the target) and the number of branching's (the number of peripheral bronchi to the target) were evaluated. RESULTS: The mean effective doses significantly differed across the four LDCTs (P <  0.001). For both central and peripheral virtual targets, there were significant differences in the accuracy of the navigation direction and the number of branching's of the VBNs across the four LDCTs (P <  0.001 for all). Regarding the accuracy of the navigation direction and the number of branching's, the areas under the curves of the ROCs were 0.9352 and 0.9324, respectively, for central virtual targets, and 0.8696 and 0.8783, respectively, for peripheral virtual targets. Youden's index indicated that the optimal effective CT scan dose for both central and peripheral virtual targets was 0.238 mSv. CONCLUSIONS: LDCT is feasible for VBN.

Factors Influencing the Diagnosis and Treatment of Latent Tuberculosis among Contacts in Congregated Settings in Korea.

BACKGROUND: This study aimed to compare the indicators (the rates of diagnosis, need for treatment, treatment initiation, and treatment completion) of management of latent tuberculosis infection (LTBI) in contacts and to identify the impact of active tuberculosis (TB) index case characteristics on the exposed population in congregated settings, such as schools, workplaces, and medical institutes. METHODS: The data of 8,648 clusters in the TB epidemiological investigation database between 2013 and 2016 were extracted and analyzed to evaluate the indicators and perform multilevel logistic regression (MLR) analyses to identify the factors affecting each indicator. RESULTS: The rates of total LTBI diagnosis, need for treatment, treatment initiation, and treatment completion were 15.2%, 10.2%, 69.4%, and 76.6%, respectively. After adjusting for other factors on MLR, the probability of diagnosis and need for treatment of latent TB in contacts was higher in most types of facilities than in schools. Conversely, treatment completion rates in these facilities were lower. Notably, the correctional institutions showed the highest odds ratio (OR) relative to school for LTBI diagnosis (OR, 6.37) and need for treatment (OR, 4.49) and the lowest OR for treatment completion (OR, 0.10). CONCLUSION: This study provided evidence for the implementation of latent TB control policies in congregated settings.