Simultaneous Analysis of Thirteen Compounds in Yeokwisan Using High-Performance Liquid Chromatography-Photodiode Array Detection and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry and Their Antioxidant Effects.

Yeokwisan (YWS) is an herbal medicine prescription consisting of six oriental herbal medicines, developed to treat reflux esophagitis. We focused on developing an analytical method capable of simultaneously quantifying 13 compounds in YWS samples using high-performance liquid chromatography-photodiode array detection (HPLC-PDA) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and exploring their antioxidant effects. All compounds examined in both analytical systems were chromatographically separated on a SunFireTM C18 (4.6 × 250 mm, 5 µm) column and an Acquity UPLC BEH C18 (2.1 × 100 mm, 1.7 µm) column using gradient elution of a water-acetonitrile mobile phase. Antioxidant effects were evaluated based on radical scavenging activity (DPPH and ABTS tests) and ferrous ion chelating activity. In two analytical methods, the coefficient of determination of the regression equation was ≥0.9965, the recovery range was 81.11-108.21% (relative standard deviation (RSD) ≤ 9.33%), and the precision was RSD ≤ 11.10%. Application of the optimized analysis conditions gave quantitative analysis results for YWS samples of 0.02-100.36 mg/g. Evaluation of the antioxidant effects revealed that baicalein and baicalin exhibit significant antioxidant activity, suggesting that they play an important role in the antioxidant effects of YWS.

Sulfuryl Fluoride Fumigation as a Quarantine Treatment for the Control of Reticulitermes speratus Kolbe (Blattodea: Rhinotermitidae) in Wood.

High-risk termites in wood imported to the Republic of Korea are currently treated with methyl bromide (MB), which has ozone-depleting properties and is highly toxic. This study evaluated the effectiveness of sulfuryl fluoride (SF) as a quarantine treatment against Reticulitermes speratus Kolbe (Blattodea: Rhinotermitidae) in wood, along with its wood sorption and penetration capacity. The LCt50 and LCt99 values for SF were 30.87 and 42.53 mg h/L at 23 °C and 151.62 and 401.9 mg h/L at 5 °C, respectively. The SF Ct values did not significantly differ between dry and wet wood at loading ratios of 10%, 30%, and 50% at both 5 °C and 23 °C (p > 0.05). In a closed wooden cube, the LCt50 and LCt99 for SF for R. speratus were 31.59 and 53.34 mg h/L, respectively, indicating an excellent wood penetration ability. SF caused 100% termite mortality with a 90% loading ratio in the scale-up trials (500 L). The SF concentration during ventilation decreased below the threshold limit value (TLV) of 5 ppm within 30 min, confirming that the working conditions were safe. This study provides a basis for the use of SF as an alternative to MB for the treatment of termites in wood.

Identification of Oil-Loving Cupriavidus necator BM3-1 for Polyhydroxyalkanoate Production and Assessing Contribution of Exopolysaccharide for Vegetable Oil Utilization.

Polyhydroxyalkanoates (PHA) have received attention owing to their biodegradability and biocompatibility, with studies exploring PHA-producing bacterial strains. As vegetable oil provides carbon and monomer precursors for poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(3HB-co-3HHx)), oil-utilizing strains may facilitate PHA production. Herein, Cupriavidus necator BM3-1, which produces 11.1 g/L of PHB with 5% vegetable oil, was selected among various novel Cupriavidus necator strains. This strain exhibited higher preference for vegetable oils over sugars, with soybean oil and tryptone determined to be optimal sources for PHA production. BM3-1 produced 33.9 g/L of exopolysaccharides (EPS), which was three-fold higher than the amount produced by H16 (10.1 g/L). EPS exhibited 59.7% of emulsification activity (EI24), higher than that of SDS and of EPS from H16 with soybean oil. To evaluate P(3HB-co-3HHx) production from soybean oil, BM3-1 was engineered with P(3HB-co-3HHx) biosynthetic genes (phaCRa, phaARe, and phaJPa). BM3-1/pPhaCJ produced 3.5 mol% of 3HHx and 37.1 g/L PHA. BM3-1/pCB81 (phaCAJ) produced 32.8 g/L PHA, including 5.9 mol% 3HHx. Physical and thermal analyses revealed that P(3HB-co-5.9 mol% 3HHx) was better than PHB. Collectively, we identified a novel strain with high vegetable oil utilization capacity for the production of EPS, with the option to engineer the strain for P(3HB-co-3HHx).

Cloning, Expression, Purification, and Characterization of Lactate Dehydrogenase from Plasmodium knowlesi: A Zoonotic Malaria Parasite.

Plasmodium knowlesi is the only Plasmodium that causes zoonotic disease among the Plasmodium that cause infection in humans. It is fatal due to its short asexual growth cycle within 24 h. Lactate dehydrogenase (LDH), an enzyme that catalyzes the final step of glycolysis, is a biomarker for diagnosing infection by Plasmodium spp. parasite. Therefore, this study aimed to efficiently produce the soluble form of P. knowlesi LDH (PkLDH) using a bacterial expression system for studying malaria caused by P. knowlesi. Recombinant pET-21a(+)-PkLDH plasmid was constructed by inserting the PkLDH gene into a pET-21a(+) expression vector. Subsequently, the recombinant plasmid was inserted into the protein-expressing Escherichia coli Rosetta(DE3) strain, and the optimal conditions for overexpression of the PkLDH protein were established using this strain. We obtained a yield of 52.0 mg/L PkLDH from the Rosetta(DE3) strain and confirmed an activity of 483.9 U/mg through experiments. This methodology for high-efficiency PkLDH production can be utilized for the development of diagnostic methods and drug candidates for distinguishing malaria caused by P. knowlesi.

Assessing the determinants of influenza and COVID-19 vaccine co-administration decisions in the elderly.

This research examines the low rate of co-administration of influenza and COVID-19 vaccines among seniors aged 65 and older in Korea, despite recommendations from authorities and academia worldwide. The study aimed to understand the influence of general characteristics and health beliefs on the vaccination choices of seniors, who were categorized into four groups based on their vaccination status: influenza only, COVID-19 only, both, or neither. A total of 400 participants, aged 65 and above, were selected through proportional stratified random sampling from five major Korean regions for a survey conducted between November 24th and December 15th, 2023. The results indicated no significant differences in general characteristics across these groups. However, regarding the health beliefs showed significant differences in perceived susceptibility and self-efficacy between the influenza-only and co-administration groups. Higher levels of perceived susceptibility and self-efficacy were associated with choosing co-administration. Contrary to previous studies focusing on safety concerns as a primary factor in vaccine hesitancy, this study highlights the role of individual health-related beliefs, particularly perceived susceptibility and self-efficacy, as critical in influencing the decision for co-administration among the elderly in Korea.

Systematic dissection of tumor-normal single-cell ecosystems across a thousand tumors of 30 cancer types.

The complexity of the tumor microenvironment poses significant challenges in cancer therapy. Here, to comprehensively investigate the tumor-normal ecosystems, we perform an integrative analysis of 4.9 million single-cell transcriptomes from 1070 tumor and 493 normal samples in combination with pan-cancer 137 spatial transcriptomics, 8887 TCGA, and 1261 checkpoint inhibitor-treated bulk tumors. We define a myriad of cell states constituting the tumor-normal ecosystems and also identify hallmark gene signatures across different cell types and organs. Our atlas characterizes distinctions between inflammatory fibroblasts marked by AKR1C1 or WNT5A in terms of cellular interactions and spatial co-localization patterns. Co-occurrence analysis reveals interferon-enriched community states including tertiary lymphoid structure (TLS) components, which exhibit differential rewiring between tumor, adjacent normal, and healthy normal tissues. The favorable response of interferon-enriched community states to immunotherapy is validated using immunotherapy-treated cancers (n = 1261) including our lung cancer cohort (n = 497). Deconvolution of spatial transcriptomes discriminates TLS-enriched from non-enriched cell types among immunotherapy-favorable components. Our systematic dissection of tumor-normal ecosystems provides a deeper understanding of inter- and intra-tumoral heterogeneity.

Prognostic implication of 1-year decline in diffusing capacity in newly diagnosed idiopathic pulmonary fibrosis.

The progression of idiopathic pulmonary fibrosis (IPF) is assessed through serial monitoring of forced vital capacity (FVC). Currently, data regarding the clinical significance of longitudinal changes in diffusing capacity for carbon monoxide (DLCO) is lacking. We investigated the prognostic implications of a 1-year decline in DLCO in 319 patients newly diagnosed with IPF at a tertiary hospital between January 2010 and December 2020. Changes in FVC and DLCO over the first year after the initial diagnosis were reviewed; a decline in FVC ≥ 5% and DLCO ≥ 10% predicted were considered significant changes. During the first year after diagnosis, a significant decline in FVC and DLCO was observed in 101 (31.7%) and 64 (20.1%) patients, respectively. Multivariable analysis showed that a 1-year decline in FVC ≥ 5% predicted (aHR 2.74, 95% CI 1.88-4.00) and 1-year decline in DLCO ≥ 10% predicted (aHR 2.31, 95% CI 1.47-3.62) were independently associated with a higher risk of subsequent mortality. The prognostic impact of a decline in DLCO remained significant regardless of changes in FVC, presence of emphysema, or radiographic indications of pulmonary hypertension. Therefore, serial monitoring of DLCO should be recommended because it may offer additional prognostic information compared with monitoring of FVC alone.

Particulate matter (PM10) exacerbates on MK-801-induced schizophrenia-like behaviors through the inhibition of ERK-CREB-BDNF signaling pathway.

Particulate matter (PM), released into the air by a variety of natural and human activities, is a key indicator of air pollution. Although PM is known as the extensive health hazard to affect a variety of illness, few studies have specifically investigated the effects of PM10 exposure on schizophrenic development. In the present study, we aimed to investigate the impact of PM10 on MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, induced schizophrenia-like behaviors in C57BL/6 mouse. Preadolescent mice were exposed PM10 to 3.2 mg/m3 concentration for 4 h/day for 2 weeks through a compartmentalized whole-body inhalation chamber. After PM10 exposure, we conducted behavioral tests during adolescence and adulthood to investigate longitudinal development of schizophrenia. We found that PM10 exacerbated schizophrenia-like behavior, such as psychomotor agitation, social interaction deficits and cognitive deficits at adulthood in MK-801-induced schizophrenia animal model. Furthermore, the reduced expression levels of brain-derived neurotrophic factor (BDNF) and the phosphorylation of BDNF related signaling molecules, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), were exacerbated by PM10 exposure in the adult hippocampus of MK-801-treated mice. Thus, our present study demonstrates that exposure to PM10 in preadolescence exacerbates the cognitive impairment in animal model of schizophrenia, which are considered to be facilitated by the decreased level of BDNF through reduced ERK-CREB expression.

Artificial Synapse Based on a δ-FAPbI3/Atomic-Layer-Deposited SnO2 Bilayer Memristor.

Halide perovskite-based resistive switching memory (memristor) has potential in an artificial synapse. However, an abrupt switch behavior observed for a formamidinium lead triiodide (FAPbI3)-based memristor is undesirable for an artificial synapse. Here, we report on the δ-FAPbI3/atomic-layer-deposited (ALD)-SnO2 bilayer memristor for gradual analogue resistive switching. In comparison to a single-layer δ-FAPbI3 memristor, the heterojunction δ-FAPbI3/ALD-SnO2 bilayer effectively reduces the current level in the high-resistance state. The analog resistive switching characteristics of δ-FAPbI3/ALD-SnO2 demonstrate exceptional linearity and potentiation/depression performance, resembling an artificial synapse for neuromorphic computing. The nonlinearity of long-term potentiation and long-term depression is notably decreased from 12.26 to 0.60 and from -8.79 to -3.47, respectively. Moreover, the δ-FAPbI3/ALD-SnO2 bilayer achieves a recognition rate of ≤94.04% based on the modified National Institute of Standards and Technology database (MNIST), establishing its potential in an efficient artificial synapse.

Ultrasound-based steatosis grading system using 2D-attenuation imaging: An individual patient data meta-analysis with external validation.

BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

Trailblazing Kr/Xe Separation: The Birth of the First Kr-Selective Material.

Efficient separation of Kr from Kr/Xe mixtures is pivotal in nuclear waste management and dark matter research. Thus far, scientists have encountered a formidable challenge: the absence of a material with the ability to selectively adsorb Kr over Xe at room temperature. This study presents a groundbreaking transformation of the renowned metal-organic framework (MOF) CuBTC, previously acknowledged for its Xe adsorption affinity, into an unparalleled Kr-selective adsorbent. This achievement stems from an innovative densification approach involving systematic compression of the MOF, where the crystal size, interparticle interaction, defects, and evacuation conditions are synergistically modulated. The resultant densified CuBTC phase exhibits exceptional mechanical resilience, radiation tolerance, and notably an unprecedented selectivity for Kr over Xe at room temperature. Simulation and experimental kinetic diffusion studies confirm reduced gas diffusion in the densified MOF, attributed to its small pore window and minimal interparticle voids. The lighter Kr element demonstrates facile surface passage and higher diffusivity within the material, while the heavier Xe encounters increased difficulty entering the material and lower diffusivity. This Kr-selective MOF not only represents a significant breakthrough in Kr separation but also demonstrates remarkable processability and scalability to kilogram levels. The findings presented herein underscore the transformative potential of engineered MOFs in addressing complex challenges, heralding a new era of Kr separation technologies.

Clinical outcomes and safety of immune checkpoint inhibitors in patients with solid tumors and paraneoplastic syndromes.

BACKGROUND: Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce. METHODS: In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT). RESULTS: Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58-74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7-3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4-3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS. CONCLUSIONS: Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

Chemoembolization versus radiofrequency ablation for single small (≤ 3 cm) hepatocellular carcinoma: a propensity score matching analysis.

OBJECTIVES: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A). MATERIALS AND METHODS: The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS). RESULTS: The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group. CONCLUSION: RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function. CLINICAL RELEVANCE STATEMENT: This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas. KEY POINTS: • The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.

S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver.

MCJ (Methylation-Controlled J protein), an endogenous repressor of the mitochondrial respiratory chain, is upregulated in multiple liver diseases but little is known about how it is regulated. S-adenosylmethionine (SAMe), the biological methyl donor, is frequently depleted in chronic liver diseases. Here, we show that SAMe negatively regulates MCJ in the liver. While deficiency in methionine adenosyltransferase alpha 1 (MATα1), enzyme that catalyzes SAMe biosynthesis, leads to hepatic MCJ upregulation, MAT1A overexpression and SAMe treatment reduced MCJ expression. We found that MCJ is methylated at lysine residues and that it interacts with MATα1 in liver mitochondria, likely to facilitate its methylation. Lastly, we observed that MCJ is upregulated in alcohol-associated liver disease, a condition characterized by reduced MAT1A expression and SAMe levels along with mitochondrial injury. MCJ silencing protected against alcohol-induced mitochondrial dysfunction and lipid accumulation. Our study demonstrates a new role of MATα1 and SAMe in reducing hepatic MCJ expression.

Transdiagnostic clustering and network analysis for questionnaire-based symptom profiling and drug recommendation in the UK Biobank and a Korean cohort.

Clinical decision support systems (CDSSs) play a critical role in enhancing the efficiency of mental health care delivery and promoting patient engagement. Transdiagnostic approaches that utilize raw psychological and biological data enable personalized patient profiling and treatment. This study introduces a CDSS incorporating symptom profiling and drug recommendation for mental health care. Among the UK Biobank cohort, we analyzed 157,348 participants for symptom profiling and 14,358 participants with a drug prescription history for drug recommendation. Among the 1307 patients in the Samsung Medical Center cohort, 842 were eligible for analysis. Symptom profiling utilized demographic and questionnaire data, employing conventional clustering and community detection methods. Identified clusters were explored using diagnostic mapping, feature importance, and scoring. For drug recommendation, we employed cluster- and network-based approaches. The analysis identified nine clusters using k-means clustering and ten clusters with the Louvain method. Clusters were annotated for distinct features related to depression, anxiety, psychosis, drug addiction, and self-harm. For drug recommendation, drug prescription probabilities were retrieved for each cluster. A recommended list of drugs, including antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics, was provided to individual patients. This CDSS holds promise for efficient personalized mental health care and requires further validation and refinement with larger datasets, serving as a valuable tool for mental healthcare providers.

Prognostic value of CT-based radiomics in grade 1-2 pancreatic neuroendocrine tumors.

BACKGROUND: Surgically resected grade 1-2 (G1-2) pancreatic neuroendocrine tumors (PanNETs) exhibit diverse clinical outcomes, highlighting the need for reliable prognostic biomarkers. Our study aimed to develop and validate CT-based radiomics model for predicting postsurgical outcome in patients with G1-2 PanNETs, and to compare its performance with the current clinical staging system. METHODS: This multicenter retrospective study included patients who underwent dynamic CT and subsequent curative resection for G1-2 PanNETs. A radiomics-based model (R-score) for predicting recurrence-free survival (RFS) was developed from a development set (441 patients from one institution) using least absolute shrinkage and selection operator-Cox regression analysis. A clinical model (C-model) consisting of age and tumor stage according to the 8th American Joint Committee on Cancer staging system was built, and an integrative model combining the C-model and the R-score (CR-model) was developed using multivariable Cox regression analysis. Using an external test set (159 patients from another institution), the models' performance for predicting RFS and overall survival (OS) was evaluated using Harrell's C-index. The incremental value of adding the R-score to the C-model was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The median follow-up periods were 68.3 and 59.7 months in the development and test sets, respectively. In the development set, 58 patients (13.2%) experienced recurrence and 35 (7.9%) died. In the test set, tumors recurred in 14 patients (8.8%) and 12 (7.5%) died. In the test set, the R-score had a C-index of 0.716 for RFS and 0.674 for OS. Compared with the C-model, the CR-model showed higher C-index (RFS, 0.734 vs. 0.662, p = 0.012; OS, 0.781 vs. 0.675, p = 0.043). CR-model also showed improved classification (NRI, 0.330, p < 0.001) and discrimination (IDI, 0.071, p < 0.001) for prediction of 3-year RFS. CONCLUSIONS: Our CR-model outperformed the current clinical staging system in prediction of the prognosis for G1-2 PanNETs and added incremental value for predicting postoperative recurrence. The CR-model enables precise identification of high-risk patients, guiding personalized treatment planning to improve outcomes in surgically resected grade 1-2 PanNETs.

LI-RADS CT and MRI Ancillary Feature Association with Hepatocellular Carcinoma and Malignancy: An Individual Participant Data Meta-Analysis.

Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To evaluate the association of LI-RADS AFs with hepatocellular carcinoma (HCC) and malignancy while adjusting for LI-RADS major features through an individual participant data (IPD) meta-analysis. Materials and Methods Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from January 2014 to January 2022 for studies evaluating the diagnostic accuracy of CT and MRI for HCC using LI-RADS version 2014, 2017, or 2018. Using a one-step approach, IPD across studies were pooled. Adjusted odds ratios (ORs) and 95% CIs were derived from multivariable logistic regression models of each AF combined with major features except threshold growth (excluded because of infrequent reporting). Liver observation clustering was addressed at the study and participant levels through random intercepts. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2. Results Twenty studies comprising 3091 observations (2456 adult participants; mean age, 59 years ± 11 [SD]; 1849 [75.3%] men) were included. In total, 89% (eight of nine) of AFs favoring malignancy were associated with malignancy and/or HCC, 80% (four of five) of AFs favoring HCC were associated with HCC, and 57% (four of seven) of AFs favoring benignity were negatively associated with HCC and/or malignancy. Nonenhancing capsule (OR = 3.50 [95% CI: 1.53, 8.01]) had the strongest association with HCC. Diffusion restriction (OR = 14.45 [95% CI: 9.82, 21.27]) and mild-moderate T2 hyperintensity (OR = 10.18 [95% CI: 7.17, 14.44]) had the strongest association with malignancy. The strongest negative associations with HCC were parallels blood pool enhancement (OR = 0.07 [95% CI: 0.01, 0.49]) and marked T2 hyperintensity (OR = 0.18 [95% CI: 0.07, 0.45]). Seventeen studies (85%) had a high risk of bias. Conclusion Most LI-RADS AFs were independently associated with HCC, malignancy, or benignity as intended when adjusting for major features. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Crivellaro in this issue.

Antimicrobial Susceptibility Patterns and Genetic Diversity of Campylobacter spp. Isolates from Patients with Diarrhea in South Korea.

This study aimed to characterize the latest antimicrobial resistance patterns and genetic diversity of Campylobacter spp. isolated from patients with acute diarrhea in Korea. In total, 371 clinical isolates (361 Campylobacter jejuni and 10 Campylobacter coli) were collected from patients with diarrhea in 106 medical institutions of six provinces during the seasonal peak (April-September 2022) in South Korea. We then assessed their antimicrobial susceptibility to eight antimicrobial agents and performed multilocus sequence typing (MLST). This study investigated the antimicrobial resistance (AMR) profiles to tetracycline (32.3%), nalidixic acid (64.9%), and ciprofloxacin (83.3%), confirming high levels of the latter even after its Korean ban in 2010. However, tetracycline resistance displayed a decreasing trend. Alternatively, significantly lower resistance rates to clindamycin (0.8%), azithromycin (0.53%), erythromycin (0.53%), and gentamicin (0.53%) as well as absolute susceptibility to florfenicol (0%) were observed. Four C. jejuni and three C. coli isolates (7/371, 1.88%) were classified as multidrug-resistant (MDR) to at least three antimicrobial classes. MLST identified a high genetic diversity with 21 clonal complexes (CCs) and sixty-six sequence types (STs), including eight novel STs. The high CC frequency of C. jejuni comprised CC21 (37.7%), CC22 (13.8%), and CC206 (9.4%), while C. coli was predominated by CC828 (90%). The high CC21 and CC828 strain prevalence in this study was consistent with their worldwide distribution. This study highlights that quinolone- and tetracycline-resistant Campylobacter circulate in Korea with diverse genotypes, providing important information that could contribute to controlling and preventing increasing antimicrobial resistance in patients.