Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

The protective roles of integrin α4ß7 and Amphiregulin-expressing innate lymphoid cells in lupus nephritis.

Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin α4ß7 in mediating renal ILC2 adhesion and function. We found that integrin α4ß7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin α4ß7 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates integrin α4ß7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin α4ß7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.

Comparison of non-contrast abbreviated MRI and ultrasound as surveillance modalities for HCC.

BACKGROUND & AIMS: Ultrasonography (US) is recommended for HCC surveillance in high-risk patients but has limited performance in detecting early-stage HCC. We aimed to compare the diagnostic performance of biannual US and annual non-contrast abbreviated magnetic resonance imaging (NC-AMRI) as HCC surveillance modalities in high-risk patients. METHODS: This prospective, multicenter cohort study enrolled participants with an estimated annual risk of HCC greater than 5% between October 2015 and April 2017. Participants underwent six rounds of HCC surveillance at 6-month intervals, with both US and NC-AMRI at rounds 1, 3, and 5, and only US at rounds 2, 4, and 6. The sensitivity, diagnostic yield (DY), and false referral rate (FRR) for HCC detection by US and NC-AMRI were compared. RESULTS: In total, 208 participants underwent 980 US and 516 NC-AMRI examinations during 30 months of follow-up. Among them, 34 HCCs were diagnosed in 31 participants, with 20 (64.5%) classified as very early-stage and 11 (35.5%) as early-stage HCC. The sensitivity of annual NC-AMRI (71.0%, 22/31) was marginally higher than that of biannual US (45.2%, 14/31; p = 0.077). NC-AMRI showed a significantly higher DY than US (4.26% vs. 1.43%, p <0.001), with a similar FRR (2.91% vs. 3.06%, p = 0.885). A simulation of alternating US and NC-AMRI at 6-month intervals yielded a sensitivity of 83.9% (26/31), significantly exceeding that of biannual US (p = 0.006). CONCLUSIONS: Annual NC-AMRI showed a marginally higher sensitivity than biannual US for HCC detection in high-risk patients. The DY of annual NC-AMRI was significantly higher than that of biannual US, without increasing the FRR. Thus, alternating US and NC-AMRI at 6-month intervals could be an optimal surveillance strategy for high-risk patients. IMPACT AND IMPLICATIONS: Current guidelines permit the use of magnetic resonance imaging (MRI) as a surveillance tool for hepatocellular carcinoma in patients in whom ultrasonography (US) is inadequate. However, the specific indications, imaging sequences, and intervals for MRI surveillance remain unclear. In our study, we found that annual non-contrast abbreviated MRI exhibited marginally higher sensitivity and significantly better diagnostic yield than biannual US in patients at high risk of hepatocellular carcinoma. Alternating US and non-contrast abbreviated MRI at 6-month intervals led to significantly improved sensitivity compared to biannual US, making it a potentially optimal surveillance strategy for high-risk patients. GOV IDENTIFIER: NCT02551250.

Prevalence, Incidence, and Treatment Pattern of Wilson's Disease Using National Health Insurance Data From 2010-2020, Korea.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive disorder in which copper (Cu) accumulates in organs, particularly in the liver and central nervous system. This study aimed to investigate the prevalence, incidence, and treatment patterns of WD patients in Korea. METHODS: National Health Insurance System (NHIS) claims data from 2010 to 2020 were analyzed. patients with WD as a primary or additional diagnosis at least once were identified using the International Classification of Diseases (ICD)-10 disease code E83.0 and a record for a registration program for rare intractable diseases in Korea. RESULTS: The average age- and sex-adjusted prevalence and incidence of WD between 2010 and 2020 were 3.06/100,000 and 0.11/100,000, respectively. The mean age of the patients with newly diagnosed WD was 21.0 ± 15.9 years. Among the 622 WD incident cases during the study period, 19.3% of the patients had liver cirrhosis and 9.2% had received liver transplantation. Psychological and neurological diseases were present in 40.7% and 48.1% of the patients, respectively. Regarding the diagnosis of WD, liver biopsy was performed in only 51.6% of new cases. D-penicillamine, trientine, or zinc were prescribed in 81.5% of the incident cases, and the treatment uptake rates decreased with increasing age. CONCLUSION: The prevalence of WD in Korea is 3.06/100,000 and approximately 1,800 patients use medical services annually. A significant proportion of patients are diagnosed at the cirrhotic stage and not treated with Cu-chelating therapeutics, suggesting the need for early diagnosis and adequate treatment to improve prognosis.

Design, synthesis of new 3H-imidazo[4,5-b]pyridine derivatives and evaluation of their inhibitory properties as mixed lineage kinase 3 inhibitors.

Mixed-lineage protein kinase 3 (MLK3) is implicated in several human cancers and neurodegenerative diseases. A series of 3H-imidazo[4,5-b]pyridine derivatives were designed, synthesized and evaluated as novel MLK3 inhibitors. A homology model of MLK3 was developed and all designed compounds were docked to assess their binding pattern and affinity toward the MLK3 active site. Based on this knowledge, we synthesized and experimentally evaluated the designed compounds. Majority of the compounds showed significant inhibition of MLK3 in the enzymatic assay. In particular, compounds 9a, 9e, 9j, 9 k, 12b and 12d exhibited IC50 values of 6, 6, 8, 11, 14 and 14 nM, respectively. Furthermore, compounds 9a, 9e, 9 k and 12b exhibited favorable physicochemical properties among these compounds.

Calf Circumference as an Indicator for Cystatin C Testing in Hospitalized Elderly Male Patients for Detecting Hidden Renal Impairment.

Serum creatinine is used to measure the estimated glomerular filtration rate (eGFR); however, it is influenced by muscle mass and may therefore overestimate renal function in patients with sarcopenia. We examined calf circumference (CC) as a convenient muscle mass evaluation tool that can potentially indicate the need to test for cystatin C instead of creatinine in elderly inpatients. We retrospectively reviewed the electronic health record of 271 inpatients aged 65 or over. CC was determined by measuring the thickest part of the nondominant calf. eGFRcys and eGFRcr were calculated using cystatin C and creatinine levels, respectively. We evaluated optimum CC cutoff values using the eGFRcys/eGFRcr ratio for detecting hidden renal impairment (HRI, defined as eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2). CC showed a significant positive correlation with the eGFRcys/eGFRcr ratio in both sexes. The areas under the receiver operating characteristic curve were 0.725 and 0.681 for males and females, respectively. CC cutoffs with a sensitivity or specificity of 90% or 95% might be used to detect HRI in males. In conclusion, utilizing the optimum cutoff, CC could be a cost-effective screening tool for detecting HRI in elderly male patients using cystatin C as an add-on test.

Predicting resection margin status of pancreatic neuroendocrine tumors on CT: performance of NCCN resectability criteria.

OBJECTIVE: To test the performance of the National Comprehensive Cancer Network (NCCN) CT resectability criteria for predicting the surgical margin status of pancreatic neuroendocrine tumor (PNET) and to identify factors associated with margin-positive resection. METHODS: Eighty patients with pre-operative CT and upfront surgery were retrospectively enrolled. Two radiologists assessed the CT resectability (resectable [R], borderline resectable [BR], unresectable [UR]) of the PNET according to NCCN criteria. Logistic regression was used to identify factors associated with resection margin status. κ statistics were used to evaluate interreader agreements. Kaplan-Meier method with log-rank test was used to estimate and compare recurrence-free survival (RFS). RESULTS: Forty-five patients (56.2%) received R0 resection and 35 (43.8%) received R1 or R2 resection. R0 resection rates were 63.6-64.2%, 20.0-33.3%, and 0% for R, BR, and UR diseases, respectively (all p ≤ 0.002), with a good interreader agreement (κ, 0.74). Tumor size (<2 cm, 2-4 cm, and >4 cm; odds ratio (OR), 9.042-18.110; all p ≤ 0.007) and NCCN BR/UR diseases (OR, 5.918; p = 0.032) were predictors for R1 or R2 resection. The R0 resection rate was 91.7% for R disease <2 cm and decreased for larger R disease. R0 resection and smaller tumor size in R disease improved RFS. CONCLUSION: NCCN resectability criteria can stratify patients with PNET into distinct groups of R0 resectability. Adding tumor size to R disease substantially improves the prediction of R0 resection, especially for PNETs <2 cm. ADVANCES IN KNOWLEDGE: Tumor size and radiologic resectability independently predicted margin status of PNETs.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Defining Integrin Tension Required for Chemotaxis of Metastatic Breast Cancer Cells in Confinement.

Cancer metastasis is affected by chemical factors and physical cues. From cell adhesion to migration, mechanical tension applied to integrin expresses on the cell membrane and physical confinement significantly regulates cancer cell behaviors. Despite the physical interplay between integrins in cells and ligands in the tumor microenvironment, quantitative analysis of integrin tension during cancer cell migration in microconfined spaces remains elusive owing to the limited experimental tools. Herein, a platform termed microconfinement tension gauge tether to monitor spatial integrin tension with single-molecule precision by analyzing the epithelial-growth-factor-induced chemotaxis of metastatic human breast cancer cells in microfluidic channels is developed. The results reveal that the metastatic cancer cells exert the strongest integrin tension in the range of 54-100 pN at the leading edges of cells during chemokinetic migration on a planar surface, while the cells exert the strongest integrin tension exceeding 100 pN at the cell rear when entering microconfinement. Further analysis demonstrates that cells undergo mesenchymal migration under high integrin tension and less confinement, which is converted to amoeboid migration under low integrin tension or high confinement. In summary, the results identify a basic mechanism underlying the mechanical interactions between integrin tension and microenvironment that determines cancer invasion and metastasis.

Core indicators related to the elimination of hepatitis B and C virus infection in South Korea: A nationwide study.

BACKGROUND/AIMS: To eliminate hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the World Health Organization (WHO) criteria in 2021, this study investigated the national core indicators representing the current status of viral hepatitis B and C in South Korea. METHODS: We analyzed the incidence, linkage-to-care, treatment, and mortality rates of HBV and HCV infection using the integrated nationwide big data of South Korea. RESULTS: According to data from 2018-2020, the incidence of acute HBV infection in South Korea was 0.71 cases per 100,000 population; tthe linkage-to-care rate was only 39.4%. Among those who need hepatitis B treatment, the treatment rate was 67.3%, which was less than 80% reported in the WHO program index. The annual liver-related mortality due to HBV was 18.85 cases per 100,000 population, exceeding the WHO target of four; the most frequent cause of death was liver cancer (54.1%). The annual incidence of newly diagnosed HCV infection was 11.9 cases per 100,000 population, which was higher than the WHO impact target of five. Among HCV-infected patients, the linkage-to-care rate was 65.5% while the treatment rate was 56.8%, which were below the targets of 90% and 80%, respectively. The liver-related annual mortality rate due to HCV infection was 2.02 cases per 100,000 population. CONCLUSION: Many of the current indicators identified in the Korean population did not satisfy the WHO criteria for validation of viral hepatitis elimination. Hence, a comprehensive national strategy should be urgently developed with continuous monitoring of the targets in South Korea.

Establishment of muscle mass-based indications for the cystatin C test in renal function evaluation.

Background: We aimed to suggest muscle mass-based criteria for using of the cystatin C test for the accurate estimated glomerular filtration rate (eGFR). Materials and methods: We recruited 138 Korean subjects and evaluated eGFRcr (derived from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) based on creatinine) was compared to eGFRcys based on cystatin C as the reference value. The skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) was used as representative of muscle mass. Calf circumference (CC) was also evaluated. We defined the patients by eGFRcr as those with values of eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2 as the detection of hidden renal impairment (DHRI). Cut-off values were determined based on muscle mass for the cases of DHRI suggesting the criteria of cystatin C test in renal function evaluation. Results: We confirmed significant negative correlation between %difference of eGFRcr from eGFRcys and SMI (r, -0.592 for male, -0.484 for female) or CC (r, -0.646 for male, -0.351 for female). SMI of 7.3 kg/m2 for males and 5.7 kg/m2 for females were suggested to be significant cutoffs for indication of cystatin C test. We also suggested CC would be valuable for cystatin C indication. Conclusion: We suggested the muscle mass-based objective criteria relating to SMI and CC that would indicate the use of cystatin C to evaluate renal function test in sarcopenic cases. Our results highlight the importance of muscle mass-based selection of renal function.

The complete chloroplast genome sequences of eight Orostachys species: Comparative analysis and assessment of phylogenetic relationships.

We analyzed the complete chloroplast genomes of eight Orostachys species and compared the sequences to those of published chloroplast genomes of the congeneric and closely related genera, Meterostachys and Hylotelephium. The total chloroplast genome length of thirteen species, including the eight species analyzed in this study and the five species analyzed in previous studies, ranged from 149,860 (M. sikokianus) to 151,707 bp (H. verticillatum). The overall GC contents of the genomes were almost identical (37.6 to 37.8%). The thirteen chloroplast genomes each contained 113 unique genes comprising 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Among the annotated genes, sixteen genes contained one or two introns. Although the genome structures of all Orostachys and Hylotelephium species were identical, Meterostachys differed in structure due to a relatively large gene block (trnS-GCU-trnS-GGA) inversion. The nucleotide diversity among the subsect. Orostachys chloroplast genomes was extremely low in all regions, and among the subsect. Appendiculatae, genus Orostachys, and all thirteen chloroplast genomes showed high values of Pi (>0.03) in one, five, or three regions. The phylogenetic analysis showed that Orostachys formed polyphyly, and subsect. Orostachys and Appendiculatae were clustered with Hylotelephium and Meterostachys, respectively, supporting the conclusion that each subsection should be considered as an independent genus. Furthermore, the data supported the taxonomic position of O. margaritifolia and O. iwarenge f. magnus, which were treated as synonyms for O. iwarenge in a previous study, as independent taxa. Our results suggested that O. ramosa and O. japonica f. polycephala were individual variations of O. malacophylla and O. japonica, respectively. The exact taxonomic position of O. latielliptica and the phylogenetic relationship among the three species, O. chongsunensis, O. malacophylla and O. ramosa, should be a topic of future study.

Protective Effect of Perilla Oil Against Dextran Sodium Sulfate-Induced Colitis in Mice Challenged with a High-Fat Diet.

This study investigated the effect of perilla oil (PO) on an ulcerative colitis mouse model. Five-week-old male C57BL/6J mice were divided into HD (high-fat diet control), HDD (high-fat diet along with dextran sodium sulfate [DSS] administration), HDD + FO, HDD + PO, and HDD + OO where HDD + FO, HDD + PO, and HDD + OO groups were treated with fish oil (FO), PO, and olive oil (OO), respectively. Biochemical analysis of serum, quantitative polymerase chain reaction, and western blotting of colon tissue were conducted to measure inflammatory marker levels. Administration of DSS resulted in colon shortening and a higher disease activity score than HD group. These symptoms were significantly reversed in the oil-treated groups. The body weight loss after DSS administration was significantly lower in the HDD + PO and HDD + OO groups than in the HDD and HDD + FO groups. PO significantly attenuated the levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß in the serum and colon. The mRNA expression levels of proinflammatory markers in the colon were reduced, whereas those of tight junction proteins and epithelial defense barrier-associated markers were increased by PO treatment. The protein expression of p-p65 was significantly lower in the PO-treated group than the HDD group. In summary, this study revealed that PO improved colitis in the DSS-induced mouse model, indicating its potential role in managing conditions such as ulcerative colitis.

Characterization of Integrin Molecular Tension of Human Breast Cancer Cells on Anisotropic Nanopatterns.

Physical interactions between cells and micro/nanometer-sized architecture presented in an extracellular matrix (ECM) environment significantly influence cell adhesion and morphology, often facilitating the incidence of diseases, such as cancer invasion and metastasis. Sensing and responding to the topographical cues are deeply associated with a physical interplay between integrins, ligands, and mechanical force transmission, ultimately determining diverse cell behavior. Thus, how the tension applied to the integrin-ligand bonds controls cells' response to the topographical cues needs to be elucidated through quantitative analysis. Here, in this brief research report, we reported a novel platform, termed "topo-tension gauge tether (TGT)," to visualize single-molecule force applied to the integrin-ligand on the aligned anisotropic nanopatterns. Using the topo-TGT assay, first, topography-induced adhesion and morphology of cancerous and normal cells were compared with the pre-defined peak integrin tension. Next, spatial integrin tensions underneath cells were identified using reconstructed integrin tension maps. As a result, we characterized each cell's capability to comply with nanotopographies and the magnitude of the spatial integrin tension. Altogether, the quantitative information on integrin tension will be a valuable basis for understanding the biophysical mechanisms underlying the force balance influencing adhesion to the topographical cues.

The complete chloroplast genome sequence of Adenophora kayasanensis Kitam. (Campanulaceae), an endemic to Korea.

Adenophora kayasanensis Kitam., belonging to the family Campanulaceae, is an important species because it is used as a type of herbal medicine and is endemic to Korea. Here, we report the complete chloroplast genome sequence of A. kayasanensis as determine by means of Illumina high-throughput sequencing. The complete cp genome was 169,433 bp in length, containing a large single copy (LSC) of 123,110 bp and a small single copy (SSC) of 8619 bp, which were separated by a pair of 29,085 bp inverted repeats (IRs). A total of 112 unique genes were annotated, consisting of 78 protein-coding genes, 30 tRNA genes, and four rRNA genes. The overall GC content is 37.7%. A maximum-likelihood (ML) tree based on 76 protein-coding genes indicated that A. kayasanensis is closely related to Adenophora racemosa. This newly sequenced chloroplast genome will be useful to those engaged in research on the phylogenetic position of A. kayasanensis and the evolution of the genus Adenophora.

Circulating mitochondrial N-formyl peptides contribute to secondary nosocomial infection in patients with septic shock.

Secondary infections typically worsen outcomes of patients recovering from septic shock. Neutrophil [polymorphonuclear leukocytes (PMNs)] migration to secondarily inoculated sites may play a key role in inhibiting progression from local bacterial inoculation to secondary infection. Mitochondrial N-formyl peptide (mtFP) occupancy of formyl peptide receptor-1 (FPR1) has been shown to suppress PMN chemotaxis. Therefore, we studied the association between circulating mtFPs and the development of secondary infection in patients with septic shock. We collected clinical data and plasma samples from patients with septic shock admitted to the intensive care unit for longer than 72 h. Impacts of circulating nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) upon clinical outcomes were analyzed. Next, the role of ND6 in PMN chemotaxis was investigated using isolated human PMNs. Studying plasma samples from 97 patients with septic shock, we found that circulating ND6 levels at admission were independently and highly associated with the development of secondary infection (odds ratio = 30.317, 95% CI: 2.904 to 316.407, P = 0.004) and increased 90-d mortality (odds ratio = 1.572, 95% CI: 1.002 to 2.465, P = 0.049). In ex vivo experiments, ND6 pretreatment suppressed FPR1-mediated PMN chemotactic responses to bacterial peptides in the presence of multiple cytokines and chemokines, despite increased nondirectional PMN movements. Circulating mtFPs appear to contribute to the development of secondary infection and increased mortality in patients with septic shock who survive their early hyperinflammatory phase. The increased susceptibility to secondary infection is probably partly mediated by the suppression of FPR1-mediated PMN chemotaxis to secondary infected sites.

Usefulness of Cone-Beam CT-Based Liver Perfusion Mapping for Evaluating the Response of Hepatocellular Carcinoma to Conventional Transarterial Chemoembolization.

We investigated the cone beam computed tomography (CBCT)-based-liver-perfusion-mapping usefulness during transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) to access treatment response and predict outcomes. From October 2016 to September 2018, 42 patients with HCCs scheduled for conventional TACE were prospectively enrolled. Three reviewers evaluated the unenhanced and contrast-enhanced CBCT and CBCT-based-liver-perfusion-mapping of each tumor. Parenchymal blood volume (PBV) was measured. The operator's judgment on the technical results was recorded. Response outcome was determined on follow-up CT or magnetic resonance imaging, according to the modified Response Evaluation Criteria in Solid Tumors. Diagnostic performance for detection of a viable tumor was evaluated using multiple logistic regression with C-statistics. CBCT-based-liver-perfusion-mapping and the maximum PBV of the tumor were significant in multiple logistic regression analysis of response (p < 0.0001, p = 0.0448, respectively), with C-statistics of 0.9540 and 0.7484, respectively. Diagnostic accuracy of operator's judgment was 79.66% (95%CI 69.39%-89.93%). Diagnostic performance of CBCT-based-liver-perfusion-mapping showed a high concordance in three reviewers. The mean PBV of tumor, maximum PBV of tumor, and mean PBV of liver significantly decreased after TACE (each p < 0.001). In ROC curve analysis, the AUC for prediction of residual tumor by the maximum PBV of tumor after TACE was 0.7523, with 80.8% sensitivity and 60.6% specificity.

Complete chloroplast genome sequence of Adenophora racemosa (Campanulaceae): Comparative analysis with congeneric species.

Adenophora racemosa, belonging to the Campanulaceae, is an important species because it is endemic to Korea. The goal of this study was to assemble and annotate the chloroplast genome of A. racemosa and compare it with published chloroplast genomes of congeneric species. The chloroplast genome was reconstructed using de novo assembly of paired-end reads generated by the Illumina MiSeq platform. The chloroplast genome size of A. racemosa was 169,344 bp. In total, 112 unique genes (78 protein-coding genes, 30 tRNAs, and 4 rRNAs) were identified. A Maximum likelihood (ML) tree based on 76 protein-coding genes divided the five Adenophora species into two clades, showing that A. racemosa is more closely related to Adenophora stricta than to Adenophora divaricata. The gene order and contents of the LSC region of A. racemosa were identical to those of A. divaricata and A. stricta, but the structure of the SSC and IRs was unique due to IR contraction. Nucleotide diversity (Pi) >0.05 was found in eleven regions among the three Adenophora species not included in sect. Remotiflorae and in six regions between two species (A. racemosa and A. stricta).

Novel fusion peptide-mediated siRNA delivery using self-assembled nanocomplex.

BACKGROUND: Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. RESULTS: Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. CONCLUSIONS: The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.

Environmental risk factors and comorbidities of primary biliary cholangitis in Korea: a case-control study.

BACKGROUND/AIMS: The risk factors for the development of primary biliary cholangitis (PBC) is unclear. This study aimed to investigate the risk factors associated with PBC in Korea through a questionnaire survey. METHODS: Consecutively enrolled 103 PBC patients from six referral hospitals and 100 age- and sex-matched community controls participated in this study. A standardized questionnaire survey including demographics, lifestyle, individual and familial medical history and reproductive history was prospectively collected and analyzed. RESULTS: The PBC patients had a mean age of 58.3 years and a female proportion of 86.4%. The age- and sex-matched controls had a similar educational level and economic status to the PBC patients. Among the lifestyle factors, the multivariable analysis showed smoking including both first-hand and second-hand (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.06 to 3.93), history of autoimmune diseases (OR, 2.46; 95% CI, 1.06 to 6.35), and family history of PBC (OR, 17.76; 95% CI, 1.77 to 2,418.74) were significantly associated with PBC, whereas alcohol intake was negatively associated with PBC. Among reproductive factors, the number of induced abortions was significantly associated with PBC, while the number of full-term deliveries was negatively associated with PBC. CONCLUSION: A family history of PBC, accompanying autoimmune diseases, and smoking were significantly associated with PBC. More induced abortions and less full-term deliveries were associated with PBC in women. In contrast, mild to moderate alcohol intake was negatively associated with PBC. Further studies are warranted to validate the results of this study and to search for clues about the pathogenesis of PBC.