Search

Background: Benign bladder tumors are rare disease entities, and insufficient studies have assessed their epidemiological characteristics. The authors investigated the prevalence of benign bladder tumors by retrospectively investigating pathology reports of transurethral resection of bladder tumor (TURBT) procedures over the past 20 years.Methods: We analyzed 1,674 pathology reports of TURBT conducted in 1,160 patients from January 1, 2000, to April 30, 2022. The prevalence of benign tumors and histological classification according to the presence of primary (group 1) and recurrent (group 2) bladder lesions were retrospectively investigated. Results: The mean age of patients was 65.2±11.5 years, and 1,284 cases (79.1%) were in men. Benign bladder tumors comprised 278 cases (248 patients) accounting for about 17.1% of the total TURBT cases (278/1,624). Furthermore, 184 patients (16.0%, 184/1,147) belonged to group 1 and 78 patients (27.4%, 78/285) belonged to group 2. Among all benign lesions that underwent TURBT, cystitis was the most common (41.0%, 114/278), and this rate was higher in group 2 (64/184 [34.8%] vs. 50/94 [53.2%], p

Osteoporosis is characterized by low bone mass and elevated structural deterioration of the bone tissue, resulting in bone weakness with an increased risk of fracture. Considering biological activities of various phytochemicals extracted from apples, we herein demonstrated the potential antiosteoporotic effects of apple-derived nanovesicles (apple NVs) using osteoblastic MC3T3-E1 cells. Apple NVs significantly stimulated the growth of MC3T3-E1 cells. The cellular alkaline phosphatase (ALP) activity was significantly upregulated in the 5

Metal-halide perovskite light-emitting diodes (PeLEDs) are considered as new-generation highly efficient luminescent materials for application in displays and solid-state lighting. Since the first successful demonstration of PeLEDs in 2014, the research on the development of efficient PeLEDs has progressed significantly. Although the device efficiency has significantly improved over a short period of time, their overall performance has not yet reached the levels of mature technologies for practical applications. Various degradation processes are the major impediment to improving the performance and stability of PeLED devices. In this review, we discuss various analysis techniques that are necessary to gain insights into the effects of various degradation mechanisms on the performance and stability of PeLEDs. Based on the causes and effects of external and internal factors, the degradation processes and associated mechanisms are examined in terms of critical physical and chemical parameters. Further, according to the progress of the current research, the challenges faced in studying degradation mechanisms are also elucidated. Given the universality of the degradation behavior, an in-depth understanding of the device degradation may promote the development of optimization strategies and further improve the performance and stability of PeLEDs.

Purpose The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.Materials and Methods Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×109 or 4×109 cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life.Results Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×109 cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001).Conclusion Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

With the development of deep learning technology and the abundance of sensors, machine vision applications that utilize vast amounts of image/video data are rapidly increasing in the autonomous vehicle, video surveillance and smart city fields. However, achieving a more compact image/video representation and lower latency solutions is challenging for such machine-based applications. Therefore, it is essential to develop a more efficient video coding standard for machine vision applications. Currently, the Moving Picture Experts Group (MPEG) is developing a new standard called video coding for machines (VCM) with two tracks, each mainly dealing with compression of the input image/video (Track 2) and compression of the features extracted from it (Track 1). In this paper, an enhanced multiscale feature compression (E-MSFC) method is proposed to efficiently compress multiscale features generated by a feature pyramid network (FPN), which is the backbone network of machine vision networks specified in the VCM evaluation framework. The proposed E-MSFC reduces the feature channels to be included in a single feature map and compresses the feature map using versatile video coding (VVC), the latest video standard, rather than the single stream feature compression (SSFC) module in the existing MSFC. In addition, the performance of the E-MSFC is further enhanced by adding a bottom-up structure to the multiscale feature fusion (MSFF) module, which performs the channel-wise reduction in the E-MSFC. Experimental results reveal that the proposed E-MSFC significantly outperforms the VCM image anchor with a BD-rate gain of up to 85.94%, which includes an additional gain of 0.96% achieved by the MSFF with the bottom-up structure.

The unique physicochemical and localized surface plasmon resonance assets of gold nanorods (GNRs) have offered combined cancer treatments with real-time diagnosis by integrating diverse theragnostic modalities into a single nanoplatform. In this work, a unique multifunctional nanohybrid material based on GNRs was designed for

Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 μg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.

Supplementary Data from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer

Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC.Significance:OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.

Supplementary Table from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer

Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis. To investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. From the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. Second, the 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. Finally, the ability to diagnose SCLC of the 7-miRNAs was estimated by area under the curve (AUC). The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC=0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers. In conclusion, our study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.

Open door laminoplasty using plates is a safe and effective procedure for multi-level cord compression. To achieve stable laminar arch, various types of plate have been developed and used. Now, we introduce two rare complications related to the laminar shelf of plate.In the first case, we used the wider laminar shelf plate because the elevated lamina did not fit well into the usual laminar shelf. During follow-up, cord compression due to laminar shelf was observed.And in the second case, the laminar shelf of plate did not fit into the elevated lamina, so we inserted it with a little bit of force. But the patient’s symptom was not improved. On CT image, the inner cortical bone of the lamina was fractured.To prevent these complications, surgeons need to consider the thickness of the lamina and the size of the laminar shelf before surgery.

This study aimed to assess how the social distancing measures impacted the choice of walking as a transportation mode, environmental preferences for walking, and walking practice among urban residents in Seoul, the capital city of South Korea. Data were collected through an online survey from September 21 to September 28, 2020, when the second level of social distancing measures was implemented; 2,112 participants aged 19 or older were included in the analysis. During COVID-19, the choice of walking as a means of transportation increased by 10.1%p, while the choice of public transportation decreased by 16.9%p. Environmental preferences for walking were more than moderate in neighborhood public open spaces, neighborhood streets, and riverside trails. Walking practice by purposes decreased significantly during COVID-19, especially in utilitarian walking. The study suggests that social distancing measures have a visible negative effect on walking practice among urban residents, as well as an invisible effect on perceived environment and choice of transportation mode in the metropolitan city. To break the physical inactivity habits established during COVID-19, guidelines for promoting walking should be developed, focusing on the frequency of walking practice. In the post-COVID-19 era, urban and transportation planning in metropolitan cities need to be reviewed focusing on the development of neighborhood assets related to walking and activation of active transportation.

In recent years, metal halide perovskites (MHPs) have attracted attention as semiconductors that achieve desirable properties for optoelectronic devices. However, two challenges—instability and the regulated nature of Pb —remain to be addressed with commercial applications. The development of Pb-free halide double perovskite (HDP) materials has gained interest and attention as a result. This family offers potential in the field of optoelectronic devices through flexible material designs and compositional adjustments. We highlight recent progress and development in halide double perovskites and encompass the synthesis, optoelectronic properties, and engineering of the electronic structures of these materials along with their applications in optoelectronic devices. Computational and data-driven statistical methods can also be used to explore mechanisms and discover promising candidate double perovskites.

As the amount of fission product released from ISLOCA was overestimated because of conservative assumptions in the past, several studies have been recently conducted to evaluate the actual release amount. Among several pathways for the ISLOCA, most studies were focused on the pathway with the highest possibility. However, different ISLOCA pathways may have different fission product release characteristics. In this study, fission product behavior was analyzed for various pathways at the Westinghouse two-loop plant using MELCOR. Four pathways are considered: the pipes from a cold leg, from a downcomer, from a hot leg to the outlet of RHR heat exchanger, and the pipe from the hot leg to the inlet of RHR pump (Pathway 1–4). According to the analysis results, cladding fails at around 2.5 h in Pathways 1 and 2, and on the other hand, about 3.3 h in Pathways 3 and 4 because the ISLOCA pathways affect the safety injection flow path. While the release amount of cesium and iodine ranges between 20 and 26% in Pathways 1 to 3, Pathway 4 allows only 5% to the environment because the break location is submerged. Also, as more than 90% of cesium released to the environment passes through the personnel door, reinforcing the pressure capacity of the doors would be a significant factor in the accident management of the ISLOCA.

Objective: Although the association between bullying victimization and internalizing problems is well established, internalizing problems experienced by foreign-born and U.S.-born racial an...

In order to reduce risks from the Steam Generator Tube Rupture (SGTR) accident and to meet safety targets, various measures have been analyzed to minimize the amount of fission product (FP) release. In this paper, we propose an introduction of a Containment Filtered Venting System (CFVS) connected to the steam generator secondary side, which can reduce the amount of FP release while minimizing adverse effects identified in the previous studies. In order to compare the effect of new equipment with the existing strategy, accident simulations using MELCOR were performed. As a result of simulations, it is confirmed that CFVS operation lowers FP release into the environment, and the release fractions are lower (minimum 0.6% of the initial inventory for Cs) than that of the strategy which intends to depressurize the primary system directly (minimum 15.2% for Cs). The sensitivity analyses identify that refill of the CFVS vessel is a dominant contributor reducing the amount of FP released. As the new strategy has the possibility of hydrogen combustion and detonation in CFVS, the installation of an igniter inside the CFVS vessel may be considered in reducing such hydrogen risk.

Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC. Significance: OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.

Past research has revealed a link between family economic hardship and children’s bullying involvement, yet research has not examined the kinds of factors that may mediate this relationship. Our study used data from the National Survey of Children’s Health and consisted of a sample of 15,797 children from 12 to 17 years of age who lived with their mothers. We found that family economic hardship was directly related to a child’s bullying behavior. Indirect associations were also found between child’s bullying and family economic hardship, violence in the home, and mother’s parental frustration. Implications for research are discussed.

Layered group-IV monochalcogenides, including GeS, GeSe, SnS, and SnSe, garner attention because of their anisotropic structures and properties. Here, we report on the growth of GeS microribbons via chemical vapor transport (CVT), which affords each of them with a low-symmetry orthorhombic structure and anisotropic optical and electronic properties. The single-crystalline nature of the GeS microribbon, which has a typical thickness of ~30 nm, is confirmed. Polarized Raman spectra reveal angle-dependent intensities that are attributed to the anisotropic layered structure of GeS microribbons. The photoluminescence (PL) spectra reveal a peak at ~1.66 eV. The angle-dependent PL and anisotropic absorption spectroscopy results provide evidence for a distinct anisotropic optical transition near the energy band edges; this phenomenon is also predicted by our density functional theory (DFT)-based calculations. Strong in-plane direct-current transport anisotropy is observed under dark and white illumination by using back-gate cross-shaped field effect transistors (CSFETs) fabricated with the GeS microribbon; significant gate-tunable conductivity is also confirmed. The strong anisotropy is further confirmed by the DFT-calculated effective mass ratio. Our findings not only support the application of GeS microribbons in anisotropic photoelectronic transistors but also provide more possibilities for other functional device applications.

AXL is a receptor tyrosine kinase (RTK) that has a various role in tumor progression such as proliferation, metastasis, angiogenesis, drug resistance and immune tolerance. Although targeting AXL exhibits an anti-cancer effects partially depending on the immune system, their molecular mechanisms have not been fully elucidated. To search the roles of AXL in immune tolerance of tumor, we generated AXL knockout (KO) mice. These AXL KO mice showed the reduced tumor growth in syngeneic LLC-1 model compared to wild type mice. To validate the mechanisms underlying the inhibition of AXL KO-derived tumor growth, we examined tumor-infiltrating lymphocytes (TIL). Compared with tumor-bearing wild type mouse, CD45-positive cells were significantly enhanced in tumor-bearing AXL KO mouse. Especially, these results were dominant in CD8-positive cells and dendritic cells (DCs). Tumor-infiltrating DCs showed the reduction of PD-L1 and Tim3 expression. In addition, the inhibition of AXL led to induce the DCs migration. In conclusion, our data demonstrated that targeting AXL may inhibit tumor growth through the activation of DCs including the enhancement of migration and reduced expression of immune check point proteins. Citation Format: Da-Som Kim, Cha Won Lee, Kyungtaek Im, Yun Jung Choi, Dong Ha Kim, Chang-Min Choi, Wonjun Ji, Jae Cheol Lee, Jin Kyung Rho. Suppression of AXL inhibits tumor growth through promotion of dendritic cell migration in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3416.

Practical lithium–oxygen batteries require a shift from pure O2 to air. CO2 traces, however, fundamentally alter the O2 electrochemistry towards Li2CO3 formation via peroxocarbonate intermediates in highly-solvating electrolytes e.g., tetraethylene glycol dimethyl ether (G4). Here, we reveal that operating temperatures (0∼70 °C) critically dictate Li2CO3-associated cell overcharges (4.60∼3.77 V), by determining temperature-dependent reaction kinetics and evolving species mobility, as analogously witnessed under pure O2-conditions. Against what is observed for Li2O2 formation in the Li–O2 cell, however, cell temperatures do not govern the crystallinity of the Li2CO3 discharge product. In agreement with experimental observations, comprehensive density functional theory calculations also uncover the effect of the temperature on the Li2CO3 precipitation mechanism and shed light on the dwindling stabilization of metastable peroxocarbonate intermediates during discharge at increasing cycling temperatures. On the other hand, during extended operation, the temperature-dependent reactants mobility in the viscous G4 electrolyte and remnant Li-deficient carbonate surfaces from precedent recharge steps play equally prominent roles on the Li2CO3 precipitation mechanism and the resulting cell capacity. Our study highlights the complexity of practical Li–O2 cells with temperature-dependent performances.

Qualitative Geographic Information Systems (QGIS) represent an emerging geospatial and qualitative approach to comprehensively understand health issues. This scoping review gathers evidence from 38 articles to illuminate when and how QGIS is used to address health issues. QGIS can contribute to recent health-related studies focusing on determinants of health and health equity at the community rather than individual level, highlight relationships between place and health, and encourage participation from people and communities in health-decision making. If more studies attempt to specify detailed data analysis methods and develop ways to use rich contexts of qualitative data, QGIS can provide greater scope for those working to solve health problems.

The emergence of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) with activating EGFR mutations is a major hindrance to treatment. We investigated the effects of p53 in primary sensitivity and acquired resistance to EGFR-TKIs in NSCLC cells. Changes in sensitivity to EGFR-TKIs were determined using p53 overexpression or knockdown in cells with activating EGFR mutations. We investigated EMT-related molecules, morphologic changes, and AXL induction to elucidate mechanisms of acquired resistance to EGFR-TKIs according to p53 status. Changes in p53 status affected primary sensitivity as well as acquired resistance to EGFR-TKIs according to cell type. Firstly, p53 silencing did not affect primary and acquired resistance to EGFR-TKIs in PC-9 cells, but it led to primary resistance to EGFR-TKIs through AXL induction in HCC827 cells. Secondly, p53 silencing in H1975 cells enhanced the sensitivity to osimertinib through the emergence of mesenchymal-to-epithelial transition, and the emergence of acquired resistance to osimertinib in p53 knockout cells was much slower than in H1975 cells. Furthermore, two cell lines (H1975 and H1975/p53KO) demonstrated the different mechanisms of acquired resistance to osimertinib. Lastly, the introduction of mutant p53-R273H induced the epithelial-to-mesenchymal transition and exerted resistance to EGFR-TKIs in cells with activating EGFR mutations. These findings indicate that p53 mutations can be associated with primary or acquired resistance to EGFR-TKIs. Thus, the status or mutations of p53 may be considered as routes to improving the therapeutic effects of EGFR-TKIs in NSCLC.

Segregation of aliovalent dopant cations is a common degradation pathway on perovskite oxide surfaces in energy conversion and catalysis applications. Here we focus on resolving quantitatively how dopant segregation is affected by oxygen chemical potential, which varies over a wide range in electrochemical and thermochemical energy conversion reactions. We employ electrochemical polarization to tune the oxygen chemical potential over many orders of magnitude. Altering the effective oxygen chemical potential causes the oxygen nonstoichiometry to change in the electrode. This then influences the mechanisms underlying the segregation of aliovalent dopants. These mechanisms are (i) the formation of oxygen vacancies that couples to the electrostatic energy of the dopant in the perovskite lattice and (ii) the elastic energy of the dopant due to cation size mismatch, which also promotes the reaction of the dopant with O₂ from the gas phase. The present study resolves these two contributions over a wide range of effective oxygen pressures. Ca-, Sr-, and Ba-doped LaMnO₃ are selected as model systems, where the dopants have the same charge but different ionic sizes. We found that there is a transition between the electrostatically and elastically dominated segregation regimes, and the transition shifted to a lower oxygen pressure with increasing cation size. This behavior is consistent with the results of our ab initio thermodynamics calculations. The present study provides quantitative insights into how the elastic energy and the electrostatic energy determine the extent of segregation for a given overpotential and atmosphere relevant to the operating conditions of perovskite oxides in energy conversion applications., Air Force Office of Scientific Research (Grant No: FA9550-16-1-0427), Austrian Science Fund (Project J 4099-N34)

The objective of this paper is to discuss the modeling principles of phenomena governing core degradation/melting and in-vessel melt relocation during severe accidents in light water reactors. The proposed modeling approach has been applied in the development of a new accident simulation package, COMPASS (COre Meltdown Progression Accident Simulation Software). COMPASS can be used either as a stand-alone tool to simulate in-vessel meltdown progression up to and including RPV failure, or as a component of an integrated simulation package being developed in Korea for the APR1400 reactor. Interestingly, since the emphasis in the development of COMPASS modeling framework has been on capturing generic mechanistic aspects of accident progression in light water reactors, several parts of the overall model should be useful for future accident studies of other reactor designs, both PWRs and BWRs.The issues discussed in the paper include the overall structure of the model, the rationale behind the formulation of the governing equations and the associated simplifying assumptions, as well as the methodology used to verify both the physical and numerical consistencies of the overall solver. Furthermore, the results of COMPASS validation against two experimental data sets (CORA and PHEBUS) are shown, as well as of the predicted accident progression at TMI-2 reactor. Keywords: Core meltdown accidents, Mechanistic modeling, Model validation