Pathogenic GATA2 genetic variants utilize an obligate enhancer mechanism to distort a multilineage differentiation program.

Mutations in genes encoding transcription factors inactivate or generate ectopic activities to instigate pathogenesis. By disrupting hematopoietic stem/progenitor cells, GATA2 germline variants create a bone marrow failure and leukemia predisposition, GATA2 deficiency syndrome, yet mechanisms underlying the complex phenotypic constellation are unresolved. We used a GATA2-deficient progenitor rescue system to analyze how genetic variation influences GATA2 functions. Pathogenic variants impaired, without abrogating, GATA2-dependent transcriptional regulation. Variants promoted eosinophil and repressed monocytic differentiation without regulating mast cell and erythroid differentiation. While GATA2 and T354M required the DNA-binding C-terminal zinc finger, T354M disproportionately required the N-terminal finger and N terminus. GATA2 and T354M activated a CCAAT/Enhancer Binding Protein-ε (C/EBPε) enhancer, creating a feedforward loop operating with the T-cell Acute Lymphocyte Leukemia-1 (TAL1) transcription factor. Elevating C/EBPε partially normalized hematopoietic defects of GATA2-deficient progenitors. Thus, pathogenic germline variation discriminatively spares or compromises transcription factor attributes, and retaining an obligate enhancer mechanism distorts a multilineage differentiation program.

Sucrosephenylpropanoid esters and isoflavonoids isolated from Belamcanda chinensis roots and their potential anti-osteoclastogenic activity.

Repeated chromatography of the CH2Cl2 and EtOAc soluble fractions from the methanol extract of Belamcanda chinensis root yielded six new sucrosephenylpropanoid esters (1-6) and twenty-one known compounds (7-27). The structures of 1-6 were elucidated using diverse nuclear magnetic resonance (NMR) techniques and high-resolution mass spectrometry (HRMS) data analysis, together with chemical methods. All the twenty-seven isolated compounds were evaluated for their anti-osteoclastogenic activities. Preliminary screening results revealed that compounds 1 and 19 exhibited strong effects against RANKL-induced osteoclast formation in RAW264.7 cells. In addition, the treatment of mouse bone marrow macrophages (BMMs) with compounds 1 and 19 significantly decreased RANKL-induced TRAP-positive multinucleated osteoclast formation in a concentration-dependent manner without affecting cell viability. Further bioassay investigation showed that compounds 1 and 19 inhibited the expression of some osteoclast-specific marker genes and the transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1) in response to RANKL. To the best of our knowledge, this is the first investigation of anti-osteoclastogenic activity for compounds isolated from B. chinensis.

Astraoleanosides E-P, oleanane-type triterpenoid saponins from the aerial parts of Astragalus membranaceus Bunge and their ß-glucuronidase inhibitory activity.

Historically, Astragalus membranaceus Bunge has been used as a beneficial medicinal plant, particularly in the Asian traditional medical systems, for the treatment of various human diseases such as stomach ulcers, diarrhea, and respiratory issues associated with phlegm. In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent ß-glucuronidase inhibitory activities, with IC50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-saccharic acid 1,4-lactone (IC50 = 20.62 ± 1.61 µM). Enzyme kinetics studies were then conducted to investigate the type of inhibition exhibited by these active compounds. In addition, the binding mechanism, key interactions, binding stability, and dynamic behavior of protein-ligand complexes were investigated through in silico approaches, such as molecular docking and molecular dynamics simulations. These findings highlight the promising potential of triterpenoid saponins from A. membranaceus as lead compounds for ß-glucuronidase inhibitors, offering new possibilities for the development of therapeutic agents targeting various diseases where ß-glucuronidase plays a crucial role.

A Causality Assessment Framework for COVID-19 Vaccines and Adverse Events at the COVID-19 Vaccine Safety Research Center.

During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024. This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels-high, moderate, limited, or insufficient-while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as "convincingly supports" ("evidence established" in the 2024 NASEM report), "favors acceptance," "favors rejection," or "inadequate to accept or reject." The CoVaSC has established an independent committee to conduct causality assessments using the weight-of-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-of-evidence framework and to detail the considerations involved in its practical application in the CoVaSC.

Artificial intelligence for ultrasound microflow imaging in breast cancer diagnosis.

PURPOSE: To develop and evaluate artificial intelligence (AI) algorithms for ultrasound (US) microflow imaging (MFI) in breast cancer diagnosis. MATERIALS AND METHODS: We retrospectively collected a dataset consisting of 516 breast lesions (364 benign and 152 malignant) in 471 women who underwent B-mode US and MFI. The internal dataset was split into training (n = 410) and test datasets (n = 106) for developing AI algorithms from deep convolutional neural networks from MFI. AI algorithms were trained to provide malignancy risk (0-100%). The developed AI algorithms were further validated with an independent external dataset of 264 lesions (229 benign and 35 malignant). The diagnostic performance of B-mode US, AI algorithms, or their combinations was evaluated by calculating the area under the receiver operating characteristic curve (AUROC). RESULTS: The AUROC of the developed three AI algorithms (0.955-0.966) was higher than that of B-mode US (0.842, P < 0.0001). The AUROC of the AI algorithms on the external validation dataset (0.892-0.920) was similar to that of the test dataset. Among the AI algorithms, no significant difference was found in all performance metrics combined with or without B-mode US. Combined B-mode US and AI algorithms had a higher AUROC (0.963-0.972) than that of B-mode US (P < 0.0001). Combining B-mode US and AI algorithms significantly decreased the false-positive rate of BI-RADS category 4A lesions from 87% to 13% (P < 0.0001). CONCLUSION: AI-based MFI diagnosed breast cancers with better performance than B-mode US, eliminating 74% of false-positive diagnoses in BI-RADS category 4A lesions.

Supply and demand: Brokerage as the new tango in home care.

The performance of home care globally is significantly impacted by the political reforms in the public and private sectors. This research investigated the Australian contexts of home care quality and the use of "brokerage" during times of change. The research utilised a qualitative post-structural approach to gather data about home care service provision through conducting semi-structured interviews of 10 Australian home care business leaders. What emerged in the discourse was how central to everyday practices was the need for business leaders to network and 'dance a political tango' to ensure quality in service provision. Illuminated was how the leaders pushed back against governmental and economic structures by using models of brokerage to compensate for economic and staffing deficiencies. This is essential for the ongoing improvement and performance of home care in the Australian social arena of caring for our most vulnerable consumers.

Spectroscopic analysis, kinetic mechanism, computational docking, and molecular dynamics of active metabolites from the aerial parts of Astragalus membranaceusBunge as tyrosinase inhibitors.

A new isoflavane derivative (2), a new natural isoflavane (6), four new oleanane-type triterpenoid saponins (23, 25, 28, and 29), and twenty three known secondary metabolites (1, 3-5, 7-22, 24, 26, and 27) were isolated from the aerial parts of Astragalus membranaceus Bunge. The chemical structures of these compounds were elucidated through spectroscopic analysis and compared with those identified in previous studies. Tyrosinase inhibition ability of isolated compounds (1-29) was evaluated. Of these, compounds 3, 4, 6, and 14 exhibited inhibitory effects, with IC50 values ranging from 24.6 to 59.2 µM. According to kinetic analysis, compounds 3 and 4 were non-competitive inhibitors of tyrosinase, whereas compounds 6 and 14 inhibited tyrosinase in uncompetitive and competitive modes, respectively. Molecular docking analysis identified that compounds 3, 4, and 6 could bind to allosteric sites and compound 14 could bind to the catalytic site of tyrosinase, which is consistent with the results of kinetic studies. Molecular dynamics behaviors of the active compounds in complex with tyrosinase were investigated via 60 ns simulation which demonstrated their high stability. These findings indicate that the aerial parts of A. membranaceus are a potential source of natural tyrosinase inhibitors.

Insights into the inhibitory activities of neolignans and diarylnonanoid derivatives from nutmeg (Myristica fragrans Houtt.) seeds on soluble epoxide hydrolase using in vitro and in silico approaches.

Two new neolignans, myrifralignans F-G (14 and 18), four new diarylnonanoid derivatives, myrifragranones A-D (21-24), and 18 known compounds were isolated and structurally elucidated from nutmeg (Myristica fragrans Houtt.) seeds. The absolute configurations of these secondary metabolites were determined using the electronic circular dichroism technique. The inhibitory potential of these isolated compounds on soluble epoxide hydrolase (sEH) was investigated for the first time. Among them, malabaricones B and C (19 and 20) and four new compounds 21-24 displayed inhibitory activities against sEH, with IC50 values ranging from 14.24 to 46.35 µM. Additionally, the binding mechanism, key binding interactions, stability, and dynamic behaviour of the active compounds with the sEH enzyme were analysed using in silico molecular docking and dynamics simulations. Our findings suggest that nutmeg could become a promising natural source for discovering and developing new sEH inhibitors.

Antibody-mediated delivery of a viral MHC-I epitope into the cytosol of target tumor cells repurposes virus-specific CD8+ T cells for cancer immunotherapy.

BACKGROUND: Redirecting pre-existing virus-specific cytotoxic CD8+ T lymphocytes (CTLs) to tumors by simulating a viral infection of the tumor cells has great potential for cancer immunotherapy. However, this strategy is limited by lack of amenable method for viral antigen delivery into the cytosol of target tumors. Here, we addressed the limit by developing a CD8+ T cell epitope-delivering antibody, termed a TEDbody, which was engineered to deliver a viral MHC-I epitope peptide into the cytosol of target tumor cells by fusion with a tumor-specific cytosol-penetrating antibody. METHODS: To direct human cytomegalovirus (CMV)-specific CTLs against tumors, we designed a series of TEDbodies carrying various CMV pp65 antigen-derived peptides. CMV-specific CTLs from blood of CMV-seropositive healthy donors were expanded for use in in vitro and in vivo experiments. Comprehensive cellular assays were performed to determine the presentation mechanism of TEDbody-mediated CMV peptide-MHC-I complex (CMV-pMHCI) on the surface of target tumor cells and the recognition and lysis by CMV-specific CTLs. In vivo CMV-pMHCI presentation and antitumor efficacy of TEDbody were evaluated in immunodeficient mice bearing human tumors. RESULTS: TEDbody delivered the fused epitope peptides into target tumor cells to be intracellularly processed and surface displayed in the form of CMV-pMHCI, leading to disguise target tumor cells as virally infected cells for recognition and lysis by CMV-specific CTLs. When systemically injected into tumor-bearing immunodeficient mice, TEDbody efficiently marked tumor cells with CMV-pMHCI to augment the proliferation and cytotoxic property of tumor-infiltrated CMV-specific CTLs, resulting in significant inhibition of the in vivo tumor growth by redirecting adoptively transferred CMV-specific CTLs. Further, combination of TEDbody with anti-OX40 agonistic antibody substantially enhanced the in vivo antitumor activity. CONCLUSION: Our study offers an effective technology for MHC-I antigen cytosolic delivery. TEDbody may thus have utility as a therapeutic cancer vaccine to redirect pre-existing anti-viral CTLs arising from previously exposed viral infections to attack tumors.

SARS-CoV-2 B.1.619 and B.1.620 Lineages, South Korea, 2021.

We report the rapid emergence of severe acute respiratory syndrome coronavirus 2 lineages B.1.619 and B.1.620 in South Korea. The surge in frequency in a relatively short time emphasizes the need for ongoing monitoring for new lineages to track potential increases in transmissibility and disease severity and reductions in vaccine efficacy.

Genomic evidence of SARS-CoV-2 reinfection in the Republic of Korea.

As the coronavirus disease 2019 (COVID-19) pandemic continues, reinfection is likely to become increasingly common. However, confirming COVID-19 reinfection is difficult because it requires whole-genome sequencing of both infections to identify the degrees of genetic differences. Since the first reported case of reinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Republic of Korea in April 2020, four additional cases were classified as suspected reinfection cases. We performed whole-genome sequencing of viral RNA extracted from swabs obtained at the initial infection and reinfection stages of these four suspected cases. The interval between initial infection and reinfection of all four suspected cases was more than 3 months. All four patients were young (10-29 years), and they displayed mild symptoms or were asymptomatic during the initial infection and reinfection episodes. The analysis of genome sequences combined with the epidemiological results revealed that only two of the four cases were confirmed as reinfection, and both were reinfected with the Epsilon variant. Due to the prolonged COVID-19 pandemic, the possibility of reinfections with SARS-CoV-2 variants is increasing, as reported in our study. Therefore, continuous monitoring of cases is necessary.

Added value of abbreviated breast magnetic resonance imaging for assessing suspicious microcalcification on screening mammography-a prospective study.

OBJECTIVES: To investigate the added diagnostic value of abbreviated breast magnetic resonance imaging (MRI) for suspicious microcalcifications on screening mammography. METHODS: This prospective study included 80 patients with suspicious calcifications on screening mammography who underwent abbreviated MRI before undergoing breast biopsy between August 2017 and September 2020. The abbreviated protocol included one pre-contrast and the first post-contrast T1-weighted series. MRI examinations were interpreted as either positive or negative based on the visibility of any significant enhancement. The positive predictive value (PPV) was compared before and after the MRI. RESULTS: Of the 80 suspicious microcalcifications, 33.8% (27/80) were malignant and 66.2% (53/80) were false positives. Abbreviated MRI revealed 33 positive enhancement lesions, and 25 and two lesions showed true-positive and false-negative findings, respectively. Abbreviated MRI increased PPV from 33.8 (27 of 80 cases; 95% CI: 26.2%, 40.8%) to 75.8% (25 of 33 cases; 95% CI: 62.1%, 85.7%). A total of 85% (45 of 53) false-positive diagnoses were reduced after abbreviated MRI assessment. CONCLUSIONS: Abbreviated MRI added significant diagnostic value in patients with suspicious microcalcifications on screening mammography, as demonstrated by a significant increase in PPV with a potential reduction in unnecessary biopsy. KEY POINTS: • Abbreviated breast magnetic resonance imaging increased the positive predictive value of suspicious microcalcifications on screening mammography from 33.8 (27/80 cases) to 75.8% (25/33 cases) (p < .01). • Abbreviated magnetic resonance imaging helped avoid unnecessary benign biopsies in 85% (45/53 cases) of lesions without missing invasive cancer.

An All-in-One Vehicle Type and License Plate Recognition System Using YOLOv4.

In smart surveillance and urban mobility applications, camera-equipped embedded platforms with deep learning technology have demonstrated applicability and effectiveness in identifying various targets. These use cases can be found in a variety of contexts and locations. It is critical to collect relevant data from the location where the application will be deployed. In this paper, we propose an integrated vehicle type and license plate recognition system using YOLOv4, which consists of vehicle type detection, license plate detection, and license plate character detection to better support the context of Korean vehicles in multilane highway and urban environments. Using our dataset of one to four multilane images, our system detected six vehicle classes and license plates with mAP of 98.0%, 94.0%, 97.1%, and 84.6%, respectively. On our dataset and a publicly available open dataset, our system demonstrated mAP of 99.3% and 99.4% for the detected license plates, respectively. From 4K high-resolution images, our system was able to detect minuscule license plates as small as 100 pixels wide. We believe that our system can be used in densely populated regions to address the high demands for enhanced visual sensitivity in smart cities and Internet-of-Things.

The Luteolinidin and Petunidin 3-O-Glucoside: A Competitive Inhibitor of Tyrosinase.

The enzyme tyrosinase plays a key role in the early stages of melanin biosynthesis. This study evaluated the inhibitory activity of anthocyanidin (1) and anthocyanins (2-6) on the catalytic reaction. Of the six derivatives examined, 1-3 showed inhibitory activity with IC50 values of 3.7 ± 0.1, 10.3 ± 1.0, and 41.3 ± 3.2 µM, respectively. Based on enzyme kinetics, 1-3 were confirmed to be competitive inhibitors with Ki values of 2.8, 9.0, and 51.9 µM, respectively. Molecular docking analysis revealed the formation of a binary encounter complex between 1-3 and the tyrosinase catalytic site. Luteolinidin (1) and petunidin 3-O-glucoside (2) may serve as tyrosinase inhibitors to block melanin production.

Suppression of Osteoarthritis progression by post-natal Induction of Nkx3.2.

Osteoarthritis (OA) is an incurable joint disease affecting 240 million elderly population, and major unmet medical needs exist for better therapeutic options for OA. During skeletal development, Nkx3.2 has been shown to promote chondrocyte differentiation and survival, but to suppress cartilage hypertrophy and blood vessel invasion. Here we show that Nkx3.2 plays a key role in osteoarthritis (OA) pathogenesis. Marked reduction of Nkx3.2 expression was observed in three different murine OA models. Consistent with these findings, analyses of surgery-induced and age-driven OA models revealed that cartilage-specific post-natal induction of Nkx3.2 can suppress OA progression in mice. These results suggest that Nkx3.2 may serve as a promising target for OA drug development.

Marivivens aquimaris sp. nov., isolated from seawater.

A Gram-stain-negative, strictly aerobic, non-flagellated, rod-shaped bacterium, designated GSB7T, was isolated from seawater collected at the Yellow Sea coast of South Korea. Catalase and oxidase activities were positive. Growth occurred at pH 6.0-9.0 (optimum pH 7.0), 10-40 °C (optimum 30 °C) and with 0-8% NaCl (optimum 1-2%). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain GSB7T belonged to the genus Marivivens, showing the sequence similarities of 96.3, 96.1, and 96.0% with Marivivens niveibacter HSLHS2T, Limimaricola hongkongensis DSM17492T, and Marivivens donghaensis AM-4T, respectively. The respiratory quinone was ubiquinone-10 and the major fatty acids were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C18:1 ω7c 11-methyl, C16:0 and C10:0 3-OH. The polar lipids comprised phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid, and five unidentified lipids. The DNA G + C content calculated from the whole-genome sequence was 60.6 mol%. On the basis of phenotypic, chemotaxonomic and genotypic characteristics presented in this study, strain GSB7T is suggested to represent a novel species of the genus Marivivens, for which the name Marivivens aquimaris sp. nov. is proposed. The type strain is GSB7T (= KCTC 82026T = JCM 34042T).

Texture analysis using machine learning-based 3-T magnetic resonance imaging for predicting recurrence in breast cancer patients treated with neoadjuvant chemotherapy.

OBJECTIVES: To determine whether texture analysis for magnetic resonance imaging (MRI) can predict recurrence in patients with breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: This retrospective study included 130 women who received NAC and underwent subsequent surgery for breast cancer between January 2012 and August 2017. We assessed common features, including standard morphologic MRI features and clinicopathologic features. We used a  commercial software and analyzed texture features from pretreatment and midtreatment MRI. A random forest (RF) method was performed to build a model for predicting recurrence. The diagnostic performance of this model for predicting recurrence was assessed and compared with those of five other machine learning classifiers using the Wald test. RESULTS: Of the 130 women, 21 (16.2%) developed recurrence at a median follow-up of 35.4 months. The RF classifier with common features including clinicopathologic and morphologic MRI features showed the lowest diagnostic performance (area under the receiver operating characteristic curve [AUC], 0.83). The texture analysis with the RF method showed the highest diagnostic performances for pretreatment T2-weighted images and midtreatment DWI and ADC maps showed better diagnostic performance than that of an analysis of common features (AUC, 0.94 vs. 0.83, p < 0.05). The RF model based on all sequences showed a better diagnostic performance for predicting recurrence than did the five other machine learning classifiers. CONCLUSIONS: Texture analysis using an RF model for pretreatment and midtreatment MRI may provide valuable prognostic information for predicting recurrence in patients with breast cancer treated with NAC and surgery. KEY POINTS: • RF model-based texture analysis showed a superior diagnostic performance than traditional MRI and clinicopathologic features (AUC, 0.94 vs.0.83, p < 0.05) for predicting recurrence in breast cancer after NAC. • Texture analysis using RF classifier showed the highest diagnostic performances (AUC, 0.94) for pretreatment T2-weighted images and midtreatment DWI and ADC maps. • RF model showed a better diagnostic performance for predicting recurrence than did the five other machine learning classifiers.

SARS-CoV-2 main protease inhibition by compounds isolated from Luffa cylindrica using molecular docking.

In this study, chemical investigation of methanol extract of the air-dried fruits of Luffa cylindrica led to the identification of a new δ-valerolactone (1), along with sixteen known compounds (2-17). Their chemical structures including the absolute configuration were elucidated by extensive spectroscopic analysis and electronic circular dichroism analysis, as well as by comparison with those reported in the literature. For the first time in literature, we have examined the binding potential of the isolated compounds to highly conserved protein, Mpro of SARS-CoV-2 using the molecular docking technique. We found that the isolated saponins (14-17) bind to the substrate-binding pocket of SARS-CoV-2 Mpro with docking energy scores of -7.13, -7.29, -7.47, and -7.54 kcal.mol-1, respectively, along with binding abilities equivalent to an already claimed N3 protease inhibitor (-7.51 kcal.mol-1).

Flavonoids from the peels of Citrus unshiu Markov. and their inhibitory effects on RANKL-induced osteoclastogenesis through the downregulation of c-Fos signaling in vitro.

Phytochemical investigation of Citrus unshiu peels led to the isolation of eight new flavonols (7-9, 11-15) and sixteen known compounds (1-6, 10, 16-24). Their structures were elucidated using spectroscopic analysis (1D, 2D NMR, and HR-MS). Besides, all isolated compounds (1-24) were evaluated for their inhibitory effects on receptor activator of RANKL-induced osteoclastogenesis in BMMs. Among them, dimethylmikanin (1), quercetogetin (2), 3,3',4',5,7,8-hexamethoxyflavone (3), 3-methoxynobiletin (4) showed a significant inhibitory effect on RANKL-induced osteoclast differentiation at a concentration of 10 µM. Moreover, 3-methoxynobiletin (4) suppressed RANKL-induced osteoclastogenesis by decreasing the number of osteoclasts and osteoclast actin-ring formation in a dose-dependent manner without causing any cytotoxic effects on BMMs. At the molecular level, 3-methoxynobiletin (4) inhibited RANKL-induced c-Fos expression and subsequently NFATc1 activation, as well as the expression of osteoclastogenesis-related marker genes c-Src and CtsK. These findings suggested that 3-methoxynobiletin (4) attenuated osteoclast differentiation by inhibiting RANKL-mediated c-Fos signaling and that it may have therapeutic potential for treating or preventing bone resorption-related diseases, such as osteoporosis.

Fully automated measurements of volumetric breast density adapted for BIRADS 5th edition: a comparison with visual assessment.

BACKGROUND: Since the 5th edition of BI-RADS was released, prior studies have compared BI-RADS and quantitative fully automated volumetric assessment, but with software packages that were not recalibrated according to the 5th edition. PURPOSE: To investigate mammographic density assessment of automated volumetric measurements recalibrated according to the BI-RADS 5th edition compared with visual assessment. MATERIAL AND METHODS: A total of 4000 full-field digital mammographic examinations were reviewed by three radiologists for the BI-RADS 5th edition density category by consensus after individual assessments. Volumetric density data obtained using Quantra and Volpara software were collected. The comparison of visual and volumetric density assessments was performed in total and according to the presence of cancer. RESULTS: Among 4000 examinations, 129 were mammograms of breast cancer. Compared to visual assessment, volumetric measurements showed higher category B (40.6% vs. 19.8%) in Quantra, and higher category D (40.4% vs. 14.7%) and lower category A (0.2% vs. 5.0%) in Volpara (P < 0.0001). All volumetric data showed a difference according to visually assessed categories and were correlated between the two volumetric measurements (P < 0.0001). The group with cancer showed a lower proportion of fatty breast than that without cancer: 17.8% vs. 46.9% for Quantra (P < 0.0001) and 9.3% vs. 21.5% for Volpara (P = 0.003). Both measurements showed significantly higher mean density data in the group with cancer than without cancer (P < 0.005 for all). CONCLUSION: Automated volumetric measurements adapted for the BI-RADS 5th edition showed different but correlated results with visual assessment and each other. Recalibration of volumetric measurement has not completely reflected the visual assessment.