RIPK3 causes mitochondrial dysfunction and albuminuria in diabetic podocytopathy through PGAM5-Drp1 signaling.

BACKGROUND: Receptor-interacting protein kinase (RIPK)3 is an essential molecule for necroptosis and its role in kidney fibrosis has been investigated using various kidney injury models. However, the relevance and the underlying mechanisms of RIPK3 to podocyte injury in albuminuric diabetic kidney disease (DKD) remain unclear. Here, we investigated the role of RIPK3 in glomerular injury of DKD. METHODS: We analyzed RIPK3 expression levels in the kidneys of patients with biopsy-proven DKD and animal models of DKD. Additionally, to confirm the clinical significance of circulating RIPK3, RIPK3 was measured by ELISA in plasma obtained from a prospective observational cohort of patients with type 2 diabetes, and estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), which are indicators of renal function, were followed up during the observation period. To investigate the role of RIPK3 in glomerular damage in DKD, we induced a DKD model using a high-fat diet in Ripk3 knockout and wild-type mice. To assess whether mitochondrial dysfunction and albuminuria in DKD take a Ripk3-dependent pathway, we used single-cell RNA sequencing of kidney cortex and immortalized podocytes treated with high glucose or overexpressing RIPK3. RESULTS: RIPK3 expression was increased in podocytes of diabetic glomeruli with increased albuminuria and decreased podocyte numbers. Plasma RIPK3 levels were significantly elevated in albuminuric diabetic patients than in non-diabetic controls (p = 0.002) and non-albuminuric diabetic patients (p = 0.046). The participants in the highest tertile of plasma RIPK3 had a higher incidence of renal progression (hazard ratio [HR] 2.29 [1.05-4.98]) and incident chronic kidney disease (HR 4.08 [1.10-15.13]). Ripk3 knockout improved albuminuria, podocyte loss, and renal ultrastructure in DKD mice. Increased mitochondrial fragmentation, upregulated mitochondrial fission-related proteins such as phosphoglycerate mutase family member 5 (PGAM5) and dynamin-related protein 1 (Drp1), and mitochondrial ROS were decreased in podocytes of Ripk3 knockout DKD mice. In cultured podocytes, RIPK3 inhibition attenuated mitochondrial fission and mitochondrial dysfunction by decreasing p-mixed lineage kinase domain-like protein (MLKL), PGAM5, and p-Drp1 S616 and mitochondrial translocation of Drp1. CONCLUSIONS: The study demonstrates that RIPK3 reflects deterioration of renal function of DKD. In addition, RIPK3 induces diabetic podocytopathy by regulating mitochondrial fission via PGAM5-Drp1 signaling through MLKL. Inhibition of RIPK3 might be a promising therapeutic option for treating DKD.

Strongylocentrotus intermedius Extract Suppresses Adiposity by Inhibiting Adipogenesis and Promoting Adipocyte Browning via AMPK Activation in 3T3-L1 Cells.

The current study aimed to determine whether Strongylocentrotus intermedius (S. intermedius) extract (SIE) exerts anti-obesity potentials employing 3T3-L1 cells as in vitro model. Herein we reported that treatment of SIE for 6 days reduced lipid accretion and TG (triglyceride) content whereas it increased the release of free glycerol. The inhibited lipid accumulation and induced lipolysis were evidenced by the downregulation of lipogenesis proteins, such as fatty acid synthase and lipoprotein lipase, and the upregulation of hormone-sensitive lipase expression. Furthermore, the downregulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α, and sterol regulatory element-binding protein 1, highlights that reduced lipid accumulation is supported by lowering adipocyte differentiation. Additionally, treatment activates brown adipocyte phenotype in 3T3-L1 cells by inducing expression of brown adipose tissue-specific proteins, such as uncoupling protein 1 (UCP-1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). Moreover, SIE induced the phosphorylation of AMP-activated protein kinase (AMPK). The pharmacological approach using AMPK inhibitor revealed that the restraining effect of SIE on adipogenesis and promotion of adipocyte browning were blocked. In GC-MS analysis, SIE was mainly composed of cholest-5-en-3-ol (36.71%) along with saturated and unsaturated fatty acids which have favorable anti-obesity potentials. These results reveal that SIE has the possibility as a lipid-lowering agent for the intervention of obesity.

Impact of standardized tobacco packaging on smoking-related behaviors and perceptions in Singapore.

INTRODUCTION: Singapore phased in standardized tobacco packaging on 1 July 2020 following a three-month grace period. This pre-post study evaluated its impacts on smoking-related behaviors and perceptions among adults who currently smoke. METHODS: Baseline and follow-up data were collected in a pre- and post-questionnaire from a cohort of 1873 Singaporean adults who were currently smoking at baseline. Baseline data were collected from December 2019 to May 2020, and follow-up data from July 2021 to September 2021. We used descriptive statistics and bivariate analyses to assess pre-post changes (Bhapkar's test, Wilcoxon signed rank test) and to identify characteristics of participants who had quit or cut down smoking at follow-up (Pearson's chi-squared, Fisher's exact test). RESULTS: At follow-up, 11.7% (n=220) had quit smoking. There was a higher proportion of those smoking non-daily (pre: 13.1%, post: 16.9%; p<0.001), and those intending to quit within the next year (pre: 14.8%, post: 17.5%; p<0.05) or six months (pre: 10.4%, post: 13.2%; p<0.01). Tobacco products were scored more negatively in relation to packaging, quality, satisfaction, value for money and overall appeal (scores pre: 15.9, post: 14.3; p<0.001), harmfulness (scores pre: 0.61, post: 0.54; p<0.05), noticing others smoking the same brand (scores pre: 1.92, post: 1.65; p<0.001), and considering quitting due to health warnings (scores pre: 0.81, post: 0.86, p<0.05). Fewer reported that some cigarette brands have higher prestige (pre: 58.0, post: 54.3%; p<0.01), and more reported using flavored cigarettes (pre: 42.2%, post: 60.1%; p<0.001) and e-cigarettes (pre: 4.2%, post: 6.1%; p<0.01). CONCLUSIONS: In Singapore, the changes observed before and after the implementation of standardized packaging suggest that it might be associated with quit-related outcomes, reduced tobacco product appeal, and increased effectiveness of graphic health warnings.

Reliability and Validity of the Martin Vigorimeter for Grip Strength Measurement in Korean Adults.

Background: Grip strength is important for fine motor skills, and one of the measurement tools for grip strength is the Martin Vigorimeter (MV) dynamometer. Studies on establishing the reliability and validity of the MV in Koreans are limited. We aimed to establish the reliability and validity of the MV for grip strength measurement in healthy Korean adults by comparing it with the Jamar dynamometer, the standard tool used by the American Society of Hand Therapists. Methods: In total, 99 healthy participants (50 men and 49 women) were enrolled. Grip strength was measured using the Jamar dynamometer and MV. Reliability and validity were assessed using the intraclass correlation coefficient (ICC) and minimal detectable change (MDC). The correlation between the measurements of the instruments was analyzed using Pearson's correlation. The effect of hand anthropometry was evaluated, and the conversion equation between the instruments was calculated. Results: MV showed excellent reliability (ICC > 0.90, p < 0.001) and validity with a high correlation (0.7 ≤ r < 0.9) with the Jamar dynamometer. The MDC was acceptable for detecting minimal clinically important differences (< 19.5%) in both instruments (Jamar: 3.4%-6.7%, MV: 3.8% to 6.3%). The grip strength measured using the MV was independent of hand anthropometry, unlike that using the Jamar dynamometer. Conclusions: This study provides insights into the relationship between the Jamar and MV instruments for measuring grip strength in Koreans. The MV is a viable alternative to the Jamar dynamometer in Koreans, offering not only reproducible and reliable measurements of grip strength but also the advantage of being unaffected by variations in hand anthropometry.

Assessment of arthrogenic quadriceps muscle inhibition by physical examination in the supine position during isometric contraction is feasible as demonstrated by electromyography: a cross-sectional study.

BACKGROUND: Preventing severe arthrogenic muscle inhibition (AMI) after knee injury is critical for better prognosis. The novel Sonnery-Cottet classification of AMI enables the evaluation of AMI severity but requires validation. This study aimed to investigate the electromyography (EMG) patterns of leg muscles in the examination position from the classification during isometric contraction to confirm its validity. We hypothesised that the AMI pattern, which is characterised by quadriceps inhibition and hamstring hypercontraction, would be detectable in the supine position during isometric contraction. METHODS: Patients with meniscal or knee ligament injuries were enrolled between August 2023 and May 2024. Surface EMG was assessed during submaximal voluntary isometric contractions (sMVIC) at 0° extension in the supine position for the vastus medialis (VM) and vastus lateralis (VL) muscles and at 20° flexion in the prone position for the semitendinosus (ST) and biceps femoris (BF) muscles. Reference values for normalisation were obtained from the EMG activity during the gait of the uninjured leg. The Kruskal-Wallis test was used to compare the activation patterns of the muscle groups within the same leg, and the post-hoc tests were conducted using the Mann-Whitney U test and Bonferroni correction. RESULTS: Electromyographic data of 40 patients with knee injuries were analyzed. During sMVIC, the extensor and flexor muscles of the injured leg showed distinct behaviours (P < 0.001), whereas the uninjured side did not (P = 0.144). In the injured leg, the VM differed significantly from the ST (P = 0.018), and the VL differed significantly from the ST and BF (P = 0.001 and P = 0.026, respectively). However, there were no statistically significant differences within the extensor muscle groups (VM and VL, P = 0.487) or flexor muscle groups (ST and BF, P = 0.377). CONCLUSION: AMI was detectable in the examination position suggested by the Sonnery-Cottet classification. The flexor and extensor muscles of the injured leg exhibited distinct activation behaviours, with inhibition predominantly occurring in the quadriceps muscles, whereas the hamstrings showed excitation.

Efficient separation of large particles and giant cancer cells using an isosceles trapezoidal spiral microchannel.

Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors. Their size, however, complicates their isolation from mainstream tumor cell populations. Standard techniques like fluorescence-activated cell sorting (FACS) rely on fluorescent labeling, introducing potential challenges in subsequent PGCC analyses. In response, we developed the Isosceles Trapezoidal Spiral Microchannel (ITSµC), a microfluidic device optimizing the Dean drag force (FD) and exploiting uniform vortices for enhanced separation. Numerical simulations highlighted ITSµC's advantage in producing robust FD compared to rectangular and standard trapezoidal channels. Empirical results confirmed its ability to segregate larger polystyrene (PS) particles (avg. diameter: 50 µm) toward the inner wall, while directing smaller ones (avg. diameter: 23 µm) outward. Utilizing ITSµC, we efficiently isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) and patient-derived cancer (PDC) cells, achieving outstanding purity, yield, and viability rates (all greater than 90%). This precision was accomplished without fluorescent markers, and the versatility of ITSµC suggests its potential in differentiating a wide range of heterogeneous cell populations.

Highly accurate measurement of the relative abundance of oral pathogenic bacteria using colony-forming unit-based qPCR.

PURPOSE: Quantitative polymerase chain reaction (qPCR) has recently been employed to measure the number of bacterial cells by quantifying their DNA fragments. However, this method can yield inaccurate bacterial cell counts because the number of DNA fragments varies among different bacterial species. To resolve this issue, we developed a novel optimized qPCR method to quantify bacterial colony-forming units (CFUs), thereby ensuring a highly accurate count of bacterial cells. METHODS: To establish a new qPCR method for quantifying 6 oral bacteria namely, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Prevotella intermedia, Fusobacterium nucleatum, and Streptococcus mutans, the most appropriate primer-probe sets were selected based on sensitivity and specificity. To optimize the qPCR for predicting bacterial CFUs, standard curves were produced by plotting bacterial CFU against Ct values. To validate the accuracy of the predicted CFU values, a spiking study was conducted to calculate the recovery rates of the predicted CFUs to the true CFUs. To evaluate the reliability of the predicted CFU values, the consistency between the optimized qPCR method and shotgun metagenome sequencing (SMS) was assessed by comparing the relative abundance of the bacterial composition. RESULTS: For each bacterium, the selected primer-probe set amplified serial-diluted standard templates indicative of bacterial CFUs. The resultant Ct values and the corresponding bacterial CFU values were used to construct a standard curve, the linearity of which was determined by a coefficient of determination (r²) >0.99. The accuracy of the predicted CFU values was validated by recovery rates ranging from 95.1% to 106.8%. The reliability of the predicted CFUs was reflected by the consistency between the optimized qPCR and SMS, as demonstrated by a Spearman rank correlation coefficient (ρ) value of 1 for all 6 bacteria. CONCLUSIONS: The CFU-based qPCR quantification method provides highly accurate and reliable quantitation of oral pathogenic bacteria.

IL-17A Cytokine-Regulated Glut1 Expression in Placenta Cells.

Trophoblasts, the principal cellular component of the placenta, play an important role in nutrient and gas exchange. Previous studies have indicated that maternal immune activation (MIA) leads to an elevation in IL-17A cytokine levels in maternal serum, subsequently influencing fetal brain development during pregnancy. In this study, we aimed to elucidate the impact of the IL-17A cytokine on placental function. First, we treated JAR and JEG-3, which is a placenta cell line, with IL-17A in a concentration-dependent or time-dependent manner and observed cell morphology and viability. It was confirmed that treatment with IL-17A or a double-stranded RNA mimic (PolyI:C) had no effect on the morphology or cell viability. IL-17A treatment increased the expression of IL-17R at the mRNA and protein levels, and Poly(I:C) increased the levels of IFNγ and TNFα. Additionally, PPARγ, known as a metabolism regulator, was increased by IL-17A treatment. Also, we observed that the expression of Glut1 and Glut3 was increased by IL-17A treatment. To confirm this, we examined the expression of transporters in the placental tissue of the MIA rodent model, and we observed that mRNA expression of glut1 and glut3 was significantly increased. However, the expression of Gltu1 and Glut3 was observed to be significantly inhibited in the brains of MIA-induced offspring. This study suggests that IL-17A increases signaling through IL-17R in the placenta and fetal brain tissue; however, there is a mechanism for regulating the expression of glucose transporters by increased IL-17A in the placenta.

Enhanced Deposition Selectivity of High-k Dielectrics by Vapor Dosing and Selective Removal of Phosphonic Acid Inhibitors.

Area-selective atomic layer deposition (AS-ALD), which provides a bottom-up nanofabrication method with atomic-scale precision, has attracted a great deal of attention as a means to alleviate the problems associated with conventional top-down patterning. In this study, we report a methodology for achieving selective deposition of high-k dielectrics by surface modification through vapor-phase functionalization of octadecylphosphonic acid (ODPA) inhibitor molecules accompanied by post-surface treatment. A comparative evaluation of deposition selectivity of ZrO2 thin films deposited with the O2 and O3 reactants was performed on SiO2, TiN, and W substrates, and we confirmed that high enough deposition selectivity over 10 nm can be achieved even after 200 cycles of ALD with the O2 reactant. Subsequently, the electrical properties of ZrO2 films deposited with O2 and O3 reactants were investigated with and without post-deposition treatment. We successfully demonstrated that high-quality ZrO2 thin films with high dielectric constants and stable antiferroelectric properties can be produced by subjecting the films to ozone, which can eliminate carbon impurities within the films. We believe that this work provides a new strategy to achieve highly selective deposition for AS-ALD of dielectric on dielectric (DoD) applications toward upcoming bottom-up nanofabrication.

Circularly Polarized Vivaldi Antennas Integrated with Septum-like Polarizer.

In this paper, two orthogonally placed Vivaldi antennas with a septum-like polarizer to generate circular polarized (CP) waves are presented. Septum polarizers have garnered attention due to their simple structure and high quality of CP waves. While a typical septum polarizer has been applied to various types of waveguides, its applicability to the substrate integrated Vivaldi antenna is demonstrated here for the first time. A pulse train-shaped polarizer is used, which is placed on one of the two Vivaldi antennas. The contours of the polarizer are optimized using a genetic algorithm to provide an equal amplitude and 90° phase difference between the two orthogonal electric fields. In contrast to typical feed networks with a 90° phase shifter, any unwanted loss caused by an electronic circuit can be greatly mitigated. The antenna prototype was fabricated, and its radiation pattern and impedance matching were measured and compared to the simulated results.

Predicting Longitudinal Cognitive Decline and Alzheimer's Conversion in Mild Cognitive Impairment Patients Based on Plasma Biomarkers.

The increasing burden of Alzheimer's disease (AD) emphasizes the need for effective diagnostic and therapeutic strategies. Despite available treatments targeting amyloid beta (Aß) plaques, disease-modifying therapies remain elusive. Early detection of mild cognitive impairment (MCI) patients at risk for AD conversion is crucial, especially with anti-Aß therapy. While plasma biomarkers hold promise in differentiating AD from MCI, evidence on predicting cognitive decline is lacking. This study's objectives were to evaluate whether plasma protein biomarkers could predict both cognitive decline in non-demented individuals and the conversion to AD in patients with MCI. This study was conducted as part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a prospective, community-based cohort. Participants were based on plasma biomarker availability and clinical diagnosis at baseline. The study included MCI (n = 50), MCI-to-AD (n = 21), and cognitively unimpaired (CU, n = 40) participants. Baseline plasma concentrations of six proteins-total tau (tTau), phosphorylated tau at residue 181 (pTau181), amyloid beta 42 (Aß42), amyloid beta 40 (Aß40), neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP)-along with three derivative ratios (pTau181/tTau, Aß42/Aß40, pTau181/Aß42) were analyzed to predict cognitive decline over a six-year follow-up period. Baseline protein biomarkers were stratified into tertiles (low, intermediate, and high) and analyzed using a linear mixed model (LMM) to predict longitudinal cognitive changes. In addition, Kaplan-Meier analysis was performed to discern whether protein biomarkers could predict AD conversion in the MCI subgroup. This prospective cohort study revealed that plasma NFL may predict longitudinal declines in Mini-Mental State Examination (MMSE) scores. In participants categorized as amyloid positive, the NFL biomarker demonstrated predictive performance for both MMSE and total scores of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-TS) longitudinally. Additionally, as a baseline predictor, GFAP exhibited a significant association with cross-sectional cognitive impairment in the CERAD-TS measure, particularly in amyloid positive participants. Kaplan-Meier curve analysis indicated predictive performance of NFL, GFAP, tTau, and Aß42/Aß40 on MCI-to-AD conversion. This study suggests that plasma GFAP in non-demented participants may reflect baseline cross-sectional CERAD-TS scores, a measure of global cognitive function. Conversely, plasma NFL may predict longitudinal decline in MMSE and CERAD-TS scores in participants categorized as amyloid positive. Kaplan-Meier curve analysis suggests that NFL, GFAP, tTau, and Aß42/Aß40 are potentially robust predictors of future AD conversion.

Association between Uric Acid Levels and the Consumption of Sugar-Sweetened Carbonated Beverages in the Korean Population: The 2016 Korea National Health and Nutrition Examination Survey.

Elevated uric acid levels are linked with obesity and diabetes. Existing research mainly examines the relationship between sugar-sweetened carbonated beverage (SSB) consumption and uric acid levels. This study explored the association between the quantity and frequency of SSB consumption and elevated uric acid levels in Korean adults. Data from 2881 participants aged 19-64 years (1066 men and 1815 women) in the 2016 Korea National Health and Nutrition Examination Survey were analyzed. Serum uric acid levels were categorized into quartiles, with the highest defined as high uric acid (men, ≥6.7 mg/dL; women, ≥4.8 mg/dL). SSB consumption was classified into quartiles (almost never, <1 cup (<200 mL), 1-3 cups (200-600 mL), ≥3 cups (≥600 mL)) and frequency into tertiles (almost never, ≤1/week, ≥2/week). Multivariate logistic regression assessed the association, with separate analyses for men and women. Increased daily SSB consumption and frequency were significantly associated with high uric acid levels in men but not in women. After adjusting for sociodemographic and health characteristics, consuming ≥3 cups (≥600 mL) of SSBs per day and SSBs ≥ 2/week were significantly associated with high serum uric acid levels in men, but this association was not observed in women. The study concludes that increased SSB intake is linked to elevated uric acid levels in Korean men, but not in women.

Adenoviral Vector System: A Comprehensive Overview of Constructions, Therapeutic Applications and Host Responses.

Adenoviral vectors are crucial for gene therapy and vaccine development, offering a platform for gene delivery into host cells. Since the discovery of adenoviruses, first-generation vectors with limited capacity have evolved to third-generation vectors flacking viral coding sequences, balancing safety and gene-carrying capacity. The applications of adenoviral vectors for gene therapy and anti-viral treatments have expanded through the use of in vitro ligation and homologous recombination, along with gene editing advancements such as CRISPR-Cas9. Current research aims to maintain the efficacy and safety of adenoviral vectors by addressing challenges such as pre-existing immunity against adenoviral vectors and developing new adenoviral vectors from rare adenovirus types and non-human species. In summary, adenoviral vectors have great potential in gene therapy and vaccine development. Through continuous research and technological advancements, these vectors are expected to lead to the development of safer and more effective treatments.

Uncovering potential CDK9 inhibitors from natural compound databases through docking-based virtual screening and MD simulations.

CONTEXT: Cyclin-dependent kinase 9 (CDK9) plays a significant role in gene regulation and RNA polymerase II transcription under basal and stimulated conditions. The upregulation of transcriptional homeostasis by CDK9 leads to various malignant tumors and therefore acts as a valuable drug target in addressing cancer incidences. Ongoing drug development endeavors targeting CDK9 have yielded numerous clinical candidate molecules currently undergoing investigation as potential CDK9 modulators, though none have yet received Food and Drug Administration (FDA) approval. METHODS: In this study, we employ in silico approaches including the molecular docking and molecular dynamics simulations for the virtual screening over the natural compounds library to identify novel promising selective CDK9 inhibitors. The compounds derived from the initial virtual screening were subsequently employed for molecular dynamics simulations and binding free energy calculations to study the compound's stability under virtual physiological conditions. The first-generation CDK inhibitor Flavopiridol was used as a reference to compare with our novel hit compound as a CDK9 antagonist. The 500-ns molecular dynamics simulation and binding free energy calculation showed that two natural compounds showed better binding affinity and interaction mode with CDK9 receptors over the reference Flavopiridol. They also showed reasonable figures in the predicted absorption, distribution, metabolism, excretion, and toxicity (ADMET) calculations as well as in computational cytotoxicity predictions. Therefore, we anticipate that the proposed scaffolds could contribute to developing potential and selective CDK9 inhibitors subjected to further validations.

Radiofrequency Ablation for the Treatment of Benign Thyroid nodules: 10-Year Experience.

BACKGROUND: Longer follow-up after radiofrequency ablation (RFA) of benign thyroid nodules is needed to understand regrowth and other causes of delayed surgery and long-term complications. METHODS: This retrospective study included consecutive patients treated with RFA for symptomatic benign nonfunctioning thyroid nodules between March 2007 and December 2010. RFA was performed according to the standard protocol. We followed up patients at 1, 6, and 12 months, then yearly, until August 2022, and calculated the volume reduction ratio (VRR) at each follow-up. We assessed the incidence of regrowth according to three published criteria, delayed surgery, and complications. The Kaplan-Meier method was used to evaluate the cumulative incidence of regrowth, and univariable and multivariable Cox regression analyses were performed to identify risk factors for regrowth. RESULTS: This study included 421 patients (mean age, 47 ± 13 years; 372 women) with 456 nodules (mean volume, 21 ± 23 mL). The median follow-up period was 90 months (interquartile range, 24-143 months). The mean VRR was >80% at 2 years, 90% at 5 years, and 94% at ≥10 years. Overall regrowth was noted in 12% (53/456) of nodules and was treated with repeat RFA (n = 33) or surgery (n = 4), or left under observation (n = 16). Thyroid nodules with ≥20 mL initial volume had significantly higher risk of regrowth compared to nodules with <10 mL initial volume (hazard ratio, 2.315 [95% confidence interval, 1.183-4.530]; p = 0.014 on multivariable Cox regression analysis). Delayed surgery was performed in 6% (26/421) of patients because of regrowth and/or persistent symptoms (n = 4), or newly detected thyroid tumors (n = 22). The overall complication rate was 2.4% (10/421), with no procedure-related deaths or long-term complications. CONCLUSION: Radiofrequency ablation is safe and effective for treating benign thyroid nodules, with a high volume reduction ratio at long-term follow-up. Regular follow-up after initial success is warranted because of the possibility of regrowth of ablated nodules and the need for delayed surgery in some patients.

Effectiveness of microvascular flow imaging for radiofrequency ablation in recurrent thyroid cancer: comparison with power Doppler imaging.

OBJECTIVES: To compare microvascular flow imaging (MVFI) and power Doppler ultrasonography imaging (PDUS) for detecting intratumoral vascularity in recurrent thyroid cancer both before and after radiofrequency ablation (RFA). METHODS: This retrospective study included 80 patients (age, 57 ± 12 years; 54 women) with 110 recurrent tumors who underwent RFA between January 2021 and June 2023. A total of 151 PDUS and MVFI image sets were analyzed (85 pre-RFA, 66 post-RFA). Two readers assessed vascularity on the images using a four-point scale with a 2-week interval between PDUS and MVFI to estimate inter-reader agreement. Intra-reader agreement was determined by reinterpreting images in reverse order (MVFI-PDUS) after a 1-month gap. Additionally, diagnostic performance for identifying viable tumors after RFA was assessed in 44 lesions using thyroid-protocol CT as a reference standard. RESULTS: MVFI demonstrated higher vascular grades than PDUS, both before (reader 1: 3.04 ± 1.15 vs. 1.93 ± 1.07, p < 0.001; reader 2: 3.20 ± 0.96 vs. 2.12 ± 1.07, p < 0.001) and after RFA (reader 1: 2.44 ± 1.28 vs. 1.67 ± 1.06, p < 0.001; reader 2: 2.62 ± 1.23 vs. 1.83 ± 0.99, p < 0.001). Inter-reader agreement was substantial (κ = 0.743) and intra-reader agreement was almost perfect (κ = 0.840). MVFI showed higher sensitivity (81.5%-88.9%) and accuracy (84.1%-86.4%) than PDUS (sensitivity: 51.9%, p < 0.01; accuracy: 63.6-70.5%, p < 0.04), without sacrificing specificity. CONCLUSION: MVFI was superior to PDUS for assessing intratumoral vascularity and showed good inter- and intra-reader agreement, highlighting its clinical value for assessing pre-RFA vascularity and accurately identifying post-RFA viable tumors in recurrent thyroid cancer. CLINICAL RELEVANCE STATEMENT: Microvascular flow imaging (MVFI) is superior to power-Doppler US for assessing intratumoral vascularity; therefore, MVFI can be a valuable tool for assessing vascularity before radiofrequency ablation (RFA) and for identifying viable tumors after RFA in patients with recurrent thyroid cancer. KEY POINTS: The value of microvascular flow imaging (MVFI) for evaluating intratumoral vascularity is unexplored. MVFI demonstrated higher vascular grades than power Doppler US before and after ablation. Microvascular flow imaging showed higher sensitivity and accuracy than power Doppler US without sacrificing specificity.

Real-world evidence of brigatinib as second-line treatment after crizotinib for ALK+ non-small cell lung cancer using South Korean claims data (K-AREAL).

PURPOSE: There is a lack of real-world data in Asian populations for brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor for patients with non-small cell lung cancer (NSCLC). This study analysed real-world outcomes and dosing patterns for brigatinib in patients with crizotinib-refractory ALK+ NSCLC in South Korea. METHODS: This retrospective, non-interventional, cohort study used South Korean Health Insurance and Review Assessment claims data for adults with ALK+ NSCLC who initiated brigatinib between 19 April 2019 and 31 March 2021 after receiving prior crizotinib. Patients' characteristics, time to discontinuation (TTD), time to dose reduction, overall survival (OS) and treatment adherence were assessed. RESULTS: The study included 174 patients (56.9% male; 27.0% with a history of brain metastases). Median duration of prior crizotinib was 17 (range 0.3-48) months. Median follow-up after brigatinib initiation was 18 (range 0-34) months. Overall, 88.5% of patients received full-dose brigatinib (180 mg/day) and 93.1% of patients were adherent (proportion of days covered ≥0.8). The median TTD was 24.9 months (95% CI 15.2-not reached). The probability of continuing treatment was 63.2% at 1 year and 51.5% at 2 years. The probability of continuing at full or peak dose was 79.7% at 1 year and 75.6% at 2 years. Median OS was not reached. The 2-year OS rate was 68.7%. CONCLUSIONS: In this first nationwide retrospective study using national insurance claim data, brigatinib demonstrated real-world clinical benefit as second-line treatment after prior crizotinib in ALK+ NSCLC patients in South Korea.

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Purpose: Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion: Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Flavor-switchable scaffold for cultured meat with enhanced aromatic properties.

Cultured meat is emerging as a new type of food that can provide animal protein in a sustainable way. Many previous studies employed various types of scaffolds to develop cultured meat with similar properties to slaughtered meat. However, important properties such as flavor were not discussed, even though they determine the quality of food. Flavor characteristics vary dramatically depending on the amount and types of amino acids and sugars that produce volatile compounds through the Maillard reaction upon cooking. In this study, a flavor-switchable scaffold is developed to release meaty flavor compounds only upon cooking temperature mimicking the Maillard reaction of slaughtered meat. By introducing a switchable flavor compound (SFC) into a gelatin-based hydrogel, we fabricate a functional scaffold that can enhance the aromatic properties of cultured meat. The temperature-responsive SFC stably remains in the scaffold during the cell culture period and can be released at the cooking temperature. Surprisingly, cultured meat fabricated with this flavor-switchable scaffold exhibits a flavor pattern similar to that of beef. This research suggests a strategy to develop cultured meat with enhanced sensorial characteristics by developing a functional scaffold which can mimic the natural cooking flavors of conventional meat.