Negative Screening AI in Ankle Stress Radiography to Reduce Workload.

RATIONALE AND OBJECTIVES: Interpreting ankle stress radiographs is subjective and time-consuming. We aimed to train an AI model that efficiently screens negative cases, assess the agreement with expert with and without AI-assistance, and compare the workload reduction. MATERIAL AND METHODS: We collected anterior draw test (ADT) and talar tilt test (TTT) ankle stress radiographs from Seoul St. Mary's Hospital and St. Vincent's Hospital. Patients with prior surgery, severe joint fusion, or incomplete images were excluded. Expert measurements of tibio-talar distance (TTD) and tibio-talar angle (TTA) served as reference, defining positive labels as TTD ≥ 8.3 mm or TTA ≥ 6.2°. We trained a VGG16 model on data from hospital A and tested it on three separate test sets (testset1, 2 from St. Mary's Hospital, and testset3 from St. Vincent's Hospital). Three readers (expert, reader2, and the collective reading reports) evaluated the test sets, with and without AI-assistance (focusing only on AI-predicted positive cases). We measured agreement with the expert using Cohen's weighted Kappa and assessed the hypothetical workload reduction. RESULTS: AI-assistance did not significantly affect agreement with the expert for any reader in all test sets. Reader2 showed moderate-substantial agreement for all test sets, while collective reports reached fair agreement. The AI alone demonstrated fair to moderate agreement with the expert. AI-assistance reduced the hypothetical workload by 68.8-89.2% for ADT and 58.3-70.4% for TTT. CONCLUSION: We successfully trained an AI model for ankle stress radiography, achieving an average of 70% workload reduction while maintaining agreement with expert radiologists.

Revisiting the impact of clinicopathologic characteristics in PD-L1 profile in a large cohort of non-small cell lung cancer.

Background: Immunotherapies using anti-programmed cell death ligand-1 (PD-L1) agents have recently shown remarkable outcomes in patients with non-small cell lung cancer (NSCLC). However, there was a poor correlation between PD-L1 expression and treatment response. Many researchers have focused on the clinicopathological factors associated with prognosis, but the results are conflicting. In the present study, we investigated the clinicopathological significance of PD-L1 overexpression in NSCLC cells. Methods: In total, 344 NSCLC cases with PD-L1 assays were retrospectively analyzed. PD-L1 expression was evaluated via immunohistochemical staining using antibodies against SP263 and SP142. The correlation between clinicopathological factors and PD-L1 expression was analyzed for various clinicopathological features. Results: PD-L1 expression significantly correlated with several poor clinicopathological factors, including the solid component of adenocarcinoma, lymphatic invasion, and recurrence. Squamous cell carcinoma, older age, and male sex were also associated with PD-L1 expression. However, we could not observe correlation between PD-L1 expression and disease-free survival (DFS). A novel finding was that lower metastasis was associated with high PD-L1 expression of SP142 in tumor-infiltrating immune cells (ICs). Conclusions: PD-L1 expression in NSCLC is associated with adverse clinicopathological features and recurrence; therefore, it could be utilized to predict poor prognosis. Furthermore, the high PD-L1 expression of SP142 in tumor-infiltrating ICs could be a potential marker for low metastasis.

Quantification of Synovial Fluid Using Magnetic Resonance Fingerprinting Multicomponent Imaging in the Articular Cartilage of the Knee.

RATIONALE AND OBJECTIVES: The purpose of this study was to verify the feasibility of magnetic resonance fingerprinting (MRF)-derived synovial fluid fraction (SFF) mapping for quantifying subvoxel-sized cartilage defects. MATERIALS AND METHODS: MRF was performed on a 3-Tesla scanner and used to derive T2 and SFF maps. An ex vivo experiment was performed using bovine bone; different numbers of holes (4, 6, 8, 10, and 12) were drilled separately on the articular surface, and SFF values were compared among the drilled areas. In a clinical study, 16 osteoarthritis patients underwent sagittal 3D fast spinecho (FSE) and MRF scanning, and knee cartilage segmentation was performed on each image. For morphologic analysis, fluid-excluded images of the SFF (FEISFF) and T2 maps (FEIT2) were generated using the cartilage segmentations, and the whole-organ magnetic resonance imaging score (WORMS) of each FEI and 3D FSE image were compared using the kappa coefficient. For quantitative analysis, intact cartilage volumes in the SFF (VSFF) and T2 maps (VT2) were calculated, and their correlations with reference to the actual cartilage volume on 3D FSE images (V3D) were evaluated. RESULTS: In the ex vivo experiment, the SFF value increased as the number of holes increased. The kappa coefficients of the WORMS were 0.80 and 0.64 in the SFF and T2 maps, respectively, and substantial to almost perfect agreement was observed in the medial tibiofemoral joint. The V3D-VSFF and V3D-VT2 correlation coefficients differed by 0.03 or more in the medial tibiofemoral joint. CONCLUSION: The MRF-derived SFF map can feasibly evaluate small, invisible cartilage defects and quantify cartilage volumes.

Affinity-Directed Site-Specific Protein Labeling and Its Application to Antibody-Drug Conjugates.

Chemically modified proteins have diverse applications; however, conventional chemo-selective methods often yield heterogeneously labeled products. To address this limitation, site-specific protein labeling holds significant potential, driving extensive research in this area. Nevertheless, site-specific modification of native proteins remains challenging owing to the complexity of their functional groups. Therefore, a method for site-selective labeling of intact proteins is aimed to design. In this study, a novel approach to traceless affinity-directed intact protein labeling is established, which leverages small binding proteins and genetic code expansion technology. By applying this method, a site-specific antibody labeling with a drug, which leads to the production of highly effective antibody-drug conjugates specifically targeting breast cancer cell lines is achieved. This approach enables traceless conjugation of intact target proteins, which is a critical advantage in pharmaceutical applications. Furthermore, small helical binding proteins can be easily engineered for various target proteins, thereby expanding their potential applications in diverse fields. This innovative approach represents a significant advancement in site-specific modification of native proteins, including antibodies. It also bears immense potential for facilitating the development of therapeutic agents for various diseases.

Ellagic acid treatment during in vitro maturation of porcine oocytes improves development competence after parthenogenetic activation and somatic cell nuclear transfer.

Ellagic acid (EA) is a natural polyphenol and a free radical scavenger with antioxidant properties. This study investigated the protective effects of EA during in vitro maturation (IVM) of porcine oocytes. To determine the optimal concentration, IVM medium was supplemented with various concentrations of EA. Treatment with 10 µM EA (10 EA) resulted in the highest cleavage rate, blastocyst formation rate, and total cell number per blastocyst and the lowest percentage of apoptotic cell in parthenogenetic blastocysts. In the 10 EA group, abnormal spindle and chromosome misalignment were rescued and the ratio of phosphorylated p44/42 to total p44/42 was increased. Furthermore, the reactive oxygen species and glutathione levels were significantly decreased and increased, respectively, and antioxidant genes (Nrf2, HO-1, CAT, and SOD1) were significantly upregulated in the 10 EA group. mRNA expression of developmental-related (CDX2, POU5F1, and SOX2) and anti-apoptotic (BCL2L1) genes was significantly upregulated in the 10 EA group, while mRNA expression of pro-apoptotic genes (BAK, FAS, and CASP3) was significantly downregulated. Ultimately, following somatic cell nuclear transfer, the blastocyst formation rate was significantly increased and the percentage of apoptotic cell in blastocysts was significantly decreased in the 10 EA group. In conclusion, addition of 10 EA to IVM medium improved oocyte maturation and the subsequent embryo development capacity through antioxidant mechanisms. These findings suggest that EA can enhance the efficiencies of assisted reproductive technologies.

Deep learning-based k-space-to-image reconstruction and super resolution for diffusion-weighted imaging in whole-spine MRI.

PURPOSE: To assess the feasibility of deep learning (DL)-based k-space-to-image reconstruction and super resolution for whole-spine diffusion-weighted imaging (DWI). METHOD: This retrospective study included 97 consecutive patients with hematologic and/or oncologic diseases who underwent DL-processed whole-spine MRI from July 2022 to March 2023. For each patient, conventional (CONV) axial single-shot echo-planar DWI (b = 50, 800 s/mm2) was performed, followed by DL reconstruction and super resolution processing. The presence of malignant lesions and qualitative (overall image quality and diagnostic confidence) and quantitative (nonuniformity [NU], lesion contrast, signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and ADC values) parameters were assessed for DL and CONV DWI. RESULTS: Ultimately, 67 patients (mean age, 63.0 years; 35 females) were analyzed. The proportions of vertebrae with malignant lesions for both protocols were not significantly different (P: [0.55-0.99]). The overall image quality and diagnostic confidence scores were higher for DL DWI (all P ≤ 0.002) than CONV DWI. The NU, lesion contrast, SNR, and CNR of each vertebral segment (P ≤ 0.04) but not the NU of the sacral segment (P = 0.51) showed significant differences between protocols. For DL DWI, the NU was lower, and lesion contrast, SNR, and CNR were higher than those of CONV DWI (median values of all segments; 19.8 vs. 22.2, 5.4 vs. 4.3, 7.3 vs. 5.5, and 0.8 vs. 0.7). Mean ADC values of the lesions did not significantly differ between the protocols (P: [0.16-0.89]). CONCLUSIONS: DL reconstruction can improve the image quality of whole-spine diffusion imaging.

Value of circulating neutrophil elastase for detecting recurrence of differentiated thyroid cancer.

Objective: The inflammatory microenvironment has been implicated in differentiated thyroid cancer (DTC). Inflammatory stimuli induce the release of components of neutrophils into extracellular space, leading to formation of neutrophil extracellular trap (NET), which can stimulate growth and progression of cancer. Generation of activated factor XII and thrombin is also involved in cancer progression. This study attempted to determine whether the level of circulating markers of NET, activated factor XII, and endogenous thrombin potential may be useful for detecting the recurrence of DTC. Methods: A total of 122 patients with DTC were recruited during the postoperative follow-up period. Measurement of the levels of circulating markers of NET (neutrophil elastase, histone-DNA complex, cell-free dsDNA), activated factor XII, and endogenous thrombin potential was performed. Results: A significantly elevated level of neutrophil elastase was detected in patients with recurrence (n = 12) compared to those without recurrence (n = 110), while significant elevation of the levels of other markers was not observed. The value for area under the curve (0.717, P = 0.018) of neutrophil elastase for detecting recurrence of DTC was superior to that (0.661, P = 0.051) of serum thyroglobulin. An elevated level of neutrophil elastase was significantly associated with recurrence of DTC independent of serum thyroglobulin. Conclusions: Because an elevated level of neutrophil elastase was detected in patients with recurrence of DTC and showed a significant association with recurrence of DTC, it can be proposed as a novel biomarker for use in detecting recurrence of DTC along with other tests.

Development of a Semiquantitative Whole-Body MRI Scoring System for Multiple Myeloma.

Background In patients with multiple myeloma (MM), the serum marker ß2-microglobulin does not always accurately reflect tumor load. In contrast, whole-body (WB) MRI has shown high sensitivity for detecting bone lesions. Purpose To develop and validate a semiquantitative WB MRI scoring system for newly diagnosed MM and to compare it with the International Staging System (ISS) and Revised ISS (R-ISS). Materials and Methods This study included two retrospective groups (group 1, July 2015 to September 2021; group 2, February 2020 to September 2021) and one prospective group (group 3, October 2021 to February 2022) of patients with newly diagnosed MM. A new scoring system for MM was developed using spine MRI scans in group 1 and WB MRI scans in group 2 that integrated three features: (a) background marrow pattern, (b) number of focal bone lesions, and (c) presence of extramedullary or paramedullary lesions. The summed total score ranged from zero to nine. The interobserver agreement for each feature was assessed using Fleiss or Cohen weighted κ. WB MRI total scores in group 3 were compared across ISS and R-ISS stages using two-way analysis of variance. Results Groups 1, 2, and 3 included 103 patients (mean age, 62.1 years ± 9.1 [SD]; 60 men), 36 patients (mean age 65.4 years ± 11.3 [SD]; 19 women), and 39 participants (mean age, 62.0 years ± 11.7 [SD]; 20 men), respectively. The interobserver agreements for the three features composing the scoring system were substantial (κ range, 0.69-0.80). WB MRI total score increased with increasing ISS stage (mean score for ISS 1, 2, and 3 was 2.2, 4.2, and 5.8, respectively; P = .009) and R-ISS stage (mean score for R-ISS 1, 2, and 3 was 2.1, 3.8, and 5.9, respectively; P = .005). Conclusion The developed WB MRI scoring system for MM demonstrated substantial observer agreement and corresponded well with ISS and R-ISS stages. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Dragan and Messiou in this issue.

Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse.

Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.

Diagnosis of Local Recurrence of Malignant Soft Tissue Tumors after Reconstructive Surgery on MRI.

PURPOSE: Magnetic resonance imaging (MRI) is useful in the diagnosis of local recurrence, but few studies have explored recurrence in MRI in patients after reconstructive surgery. The purpose of this study was to analyze MRI findings of locoregional recurrence following reconstructive surgery after malignant soft tissue tumor resection. METHOD: Fifty-three postoperative MRIs from 37 patients who underwent reconstructive surgery after malignant soft tissue tumor resection were retrospectively reviewed. A total of 76 enhancing lesions, including 40 locoregional recurrences and 36 postoperative changes, were analyzed regarding morphology (location on the transplanted tissue, border, and shape) and the signals on T1- and T2-weighted imaging (T1WI, T2WI), fat-suppressed (FS) T2WI, and contrast-enhanced FS T1WI. Diffusion-weighted imaging with an apparent diffusion coefficient was assessed. A chi-squared test and Fisher's exact test were used for statistical analysis. RESULTS: The most common site of recurrent tumors and postoperative changes was the peripheral margin on transplanted tissue (63% and 61%, respectively p = 0.907). Recurrent tumors commonly appeared with well-defined borders (75%) as well as nodular appearance (98%), hyperintensity on T2WI (85%) and FS-T2WI (95%), isointensity on T1WI (65%), impeded water diffusion (55%), and intense (50%) or moderate (45%) enhancement. Postoperative changes showed ill-defined borders (75%), nodular appearance (56%), facilitated water diffusion (69%), and moderate (86%) enhancement, which were significantly different from those of recurrent tumors (p ≤ 0.020). CONCLUSIONS: Common and partitioning MRI features of locoregional recurrence were well-defined borders, nodular shape, impeded water diffusion, and intense enhancement. Peripheral margins on transplanted tissue were common sites in both recurrent tumors and postoperative changes.

Evaluation of a Series of Turnip Mosaic Virus Chimeric Clones Reveals Two Amino Acid Sites Critical for Systemic Infection in Chinese Cabbage.

Two infectious clones of turnip mosaic virus (TuMV), pKBC-1 and pKBC-8, with differential infectivity in Chinese cabbage (Brassica rapa subsp. pekinensis), were obtained. Both infected Nicotiana benthamiana systemically, inducing similar symptoms, whereas only virus KBC-8 infected Chinese cabbage systemically. To identify the determinants affecting infectivity on Chinese cabbage, chimeric clones were constructed by restriction fragment exchange between the parental clones and tested on several Chinese cabbage cultivars. Chimeric clones p1N8C and p8N1C demonstrated that the C-terminal portion of the polyprotein determines systemic infection of Chinese cabbage despite only three amino acid differences in this region, in the cylindrical inclusion (CI), viral protein genome-linked (VPg), and coat protein (CP). A second pair of hybrid constructs, pHindIII-1N8C and pHindIII-8N1C, failed to infect cultivars CR Victory and Jinseonnorang systemically, yet pHindIII-1N8C caused hypersensitive response-like lesions on inoculated leaves of these cultivars, and could systemically infect cultivars CR Chusarang and Jeongsang; this suggests that R genes effective against TuMV may exist in the first two cultivars but not the latter two. Constructs with single amino acid changes in both VPg (K2045E) and CP (Y3095H) failed to infect Chinese cabbage, implying that at least one of these two amino acid substitutions is essential for successful infection on Chinese cabbage. Successful infection by mutant KBC-8-CP-H and delayed infection with mutant HJY1-VPg-E following mutation or reversion suggested that VPg (2045K) is the residue required for infection of Chinese cabbage and involved in the interaction between VPg and eukaryotic initiation factor eIF(iso)4E, confirmed by yeast two-hybrid assay.

Discordant renal progression of Fabry disease in male monozygotic twins: a case report.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A (α-GAL). Clinical phenotypes tend to vary in monozygotic female twins because mutations are located on the X-chromosome, whereas similar phenotypes are found in male monozygotic twins. Here we report the case of male monozygotic twins with FD presenting with distinguishable renal phenotypes. Case: A 49-year-old male patient who visited the hospital with proteinuria 14 years prior was readmitted for the same issue. His monozygotic twin brother had started hemodialysis 6 months prior due to renal failure of unknown origin. The patient's renal function was within the normal range, while his spot urine protein-to-creatinine ratio was 557 mg/g. Echocardiography revealed left ventricular hypertrophy (LVH). The findings of a renal biopsy were consistent with FD. Genetic testing identified a c.656T>C mutation in the GLA gene, and α-GAL activity was significantly decreased. Genetic screening of his family clarified that his mother, older sister, twin brother, and his daughter had the same genetic mutations. The patient received enzyme replacement therapy 34 times. Subsequently, migalastat was initiated that continues today. Renal function and proteinuria remain stable, and the LVH has mildly improved. Conclusion: This is the first case of male monozygotic twins expressing different progressions of FD. Our findings demonstrate the possibility that environmental or epigenetic factors may critically influence genotype-phenotype discordance.

Ensemble learning-based radiomics with multi-sequence magnetic resonance imaging for benign and malignant soft tissue tumor differentiation.

Many previous studies focused on differentiating between benign and malignant soft tissue tumors using radiomics model based on various magnetic resonance imaging (MRI) sequences, but it is still unclear how to set up the input radiomic features from multiple MRI sequences. Here, we evaluated two types of radiomics models generated using different feature incorporation strategies. In order to differentiate between benign and malignant soft tissue tumors (STTs), we compared the diagnostic performance of an ensemble of random forest (R) models with single-sequence MRI inputs to R models with pooled multi-sequence MRI inputs. One-hundred twenty-five STT patients with preoperative MRI were retrospectively included and consisted of training (n = 100) and test (n = 25) sets. MRI included T1-weighted (T1-WI), T2-weighted (T2-WI), contrast-enhanced (CE)-T1-WI, diffusion-weighted images (DWIs, b = 800 sec/mm2) and apparent diffusion coefficient (ADC) maps. After tumor segmentation on each sequence, 100 original radiomic features were extracted from each sequence image and divided into three-feature sets: T features from T1- and T2-WI, CE features from CE-T1-WI, and D features from DWI and ADC maps. Four radiomics models were built using Lasso and R with four combinations of three-feature sets as inputs: T features (R-T), T+CE features (R-C), T+D features (R-D), and T+CE+D features (R-A) (Type-1 model). An ensemble model was built by soft voting of five, single-sequence-based R models (Type-2 model). AUC, sensitivity, specificity, and accuracy of each model was calculated with five-fold cross validation. In Type-1 model, AUC, sensitivity, specificity, and accuracy were 0.752, 71.8%, 61.1%, and 67.2% in R-T; 0.756, 76.1%, 70.4%, and 73.6% in R-C; 0.750, 77.5%, 63.0%, and 71.2% in R-D; and 0.749, 74.6%, 61.1%, and 68.8% R-A models, respectively. AUC, sensitivity, specificity, and accuracy of Type-2 model were 0.774, 76.1%, 68.5%, and 72.8%. In conclusion, an ensemble method is beneficial to incorporate features from multi-sequence MRI and showed diagnostic robustness for differentiating malignant STTs.

Comparative study on gamma-ray detectors for in-situ ocean radiation monitoring system.

Large-sized crystals and state-of-the-art photosensors are desirable to cope with low environmental radioactivity (e.g., 1-2 Bq∙m-3137Cs in surface seawater) for homeland security purposes. We compared the performances of two different gamma-ray detector assemblies, GAGG crystal + silicon photomultiplier (SiPM) and NaI(Tl) crystal + photomultiplier tube, for our mobile in-situ ocean radiation monitoring system. We performed energy calibration, followed by water tank experiments with varying the depth of a137Cs point source. Experimental energy spectra were compared with MCNP-simulated spectra with identical setup and the consistency was validated. We finally assessed the detection efficiency and minimum detectable activity (MDA) of the detectors. Both GAGG and NaI detectors exhibited favorable energy resolutions (7.98 ± 0.13% and 7.01 ± 0.58% at 662 keV, respectively) and MDAs (33.1 ± 0.0645 and 13.5 ± 0.0327 Bq∙m-3 for 24-h 137Cs measurement, respectively). Matching the geometry of the GAGG crystal with that of the NaI crystal, the GAGG detector outperformed the NaI detector. The results demonstrated that the GAGG detector is potentially advantageous over the NaI detector in detection efficiency and compactness.

Extract of Aster koraiensis Nakai Leaf Ameliorates Memory Dysfunction via Anti-inflammatory Action.

Aster koraiensis Nakai (AK) leaf reportedly ameliorates health problems, such as diabetes. However, the effects of AK on cognitive dysfunction or memory impairment remain unclear. This study investigated whether AK leaf extract could attenuate cognitive impairment. We found that AK extract reduced the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, phosphorylated-tau (p-tau), and the expression of inflammatory proteins in lipopolysaccharide- or amyloid-ß-treated cells. AK extract exhibited inhibitory activity of control specific binding on N-methyl-D-aspartate (NMDA) receptors. Scopolamine-induced AD models were used chronically in rats and acutely in mice. Relative to negative controls (NC), hippocampal choline acetyltransferase (ChAT) and B-cell lymphoma 2 (Bcl2) activity was increased in rats chronically treated with scopolamine and fed an AK extract-containing diet. In the Y-maze test, spontaneous alterations were increased in the AK extract-fed groups compared to NC. Rats administered AK extract showed increased escape latency in the passive avoidance test. In the hippocampus of rats fed a high-AK extract diet (AKH), the expression of neuroactive ligand-receptor interaction-related genes, including Npy2r, Htr2c, and Rxfp1, was significantly altered. In the Morris water maze assay of mice acutely treated with scopolamine, the swimming times in the target quadrant of AK extract-treated groups increased significantly to the levels of the Donepezil and normal groups. We used Tg6799 Aß-overexpressing 5XFAD transgenic mice to investigate Aß accumulation in animals. In the AD model using 5XFAD, the administration of AK extract decreased amyloid-ß (Aß) accumulation and increased the number of NeuN antibody-reactive cells in the subiculum relative to the control group. In conclusion, AK extract ameliorated memory dysfunction by modulating ChAT activity and Bcl2-related anti-apoptotic pathways, affecting the expression of neuroactive ligand-receptor interaction-related genes and inhibiting Aß accumulation. Therefore, AK extract could be a functional material improving cognition and memory.

Differentiating Multiple Myeloma and Osteolytic Bone Metastases on Contrast-Enhanced Computed Tomography Scans: The Feasibility of Radiomics Analysis.

Osteolytic lesions can be seen in both multiple myeloma (MM), and osteolytic bone metastasis on computed tomography (CT) scans. We sought to assess the feasibility of a CT-based radiomics model to distinguish MM from metastasis. This study retrospectively included patients with pre-treatment thoracic or abdominal contrast-enhanced CT from institution 1 (training set: 175 patients with 425 lesions) and institution 2 (external test set: 50 patients with 85 lesions). After segmenting osteolytic lesions on CT images, 1218 radiomics features were extracted. A random forest (RF) classifier was used to build the radiomics model with 10-fold cross-validation. Three radiologists distinguished MM from metastasis using a five-point scale, both with and without the assistance of RF model results. Diagnostic performance was evaluated using the area under the curve (AUC). The AUC of the RF model was 0.807 and 0.762 for the training and test set, respectively. The AUC of the RF model and the radiologists (0.653-0.778) was not significantly different for the test set (p ≥ 0.179). The AUC of all radiologists was significantly increased (0.833-0.900) when they were assisted by RF model results (p < 0.001). In conclusion, the CT-based radiomics model can differentiate MM from osteolytic bone metastasis and improve radiologists' diagnostic performance.

Tau acetylation at K280 regulates tau phosphorylation.

PURPOSE/AIM OF THE STUDY: Accumulation of hyperphosphorylated tau is a key pathological finding of Alzheimer's disease. Recently, acetylation of tau is emerging as another key pathogenic modification, especially regarding the acetylation of tau at K280 of the hexapeptide 275VQIINK280, a critical sequence in driving tau aggregation. However, the relationship between these two key post-translational modifications is not well known. In this study, effect of acetylation of tau at K280 on tau phosphorylation profile was investigated. MATERIALS AND METHODS: The human neuroblastoma cell line, SH-SY5Y, was transfected with p300 acetyltransferase and tau to induce acetylation of tau. Phosphorylation profile after acetylation was evaluated on western blot. K280A-mutant tau was transfected to investigate the effect of acetylation of tau at K280 on tau phosphorylation profile. RESULTS: Overexpression of p300 acetyltransferase in tau-transfected SH-SY5Y human neuroblastoma cells increased acetylation of tau. Meanwhile, tau and its phosphorylation also increased at various sites such as S199/202, S202/T205, T231, and S422, but not at S396. However, blocking acetylation only at K280 with K280A-mutant tau reversed the increased phosphorylation of tau at S202/T205, T231, and S422, but not at S199/202 or S396. CONCLUSION: Here we identified tau phosphorylation profile in the context of p300-induced acetylation and K280A-mutant tau, demonstrating that tau acetylation affects phosphorylation differently by residues and that acetylation at K280 is a determinant of phosphorylation at some residues in the context of pathologic acetyltransferase activity. Yet, our results suggest there is a complex interplay yet to be explored between tau acetylation with tau phosphorylation.

Diagnosis of Marginal Infiltration in Soft Tissue Sarcoma by Radiomics Approach Using T2-Weighted Dixon Sequence.

BACKGROUND: Determination of preoperative soft tissue sarcoma (STS) margin is crucial for patient prognosis. PURPOSE: To evaluate diagnostic performance of radiomics model using T2-weighted Dixon sequence for infiltration degree of STS margin. STUDY TYPE: Retrospective. POPULATION: Seventy-two STS patients consisted of training (n = 58) and test (n = 14) sets. FIELD STRENGTH/SEQUENCE: A 3.0 T; T2-weighted Dixon images. ASSESSMENT: Pathologic result of marginal infiltration in STS (circumscribed margin; n = 27, group 1, focally infiltrative margin; n = 31, group 2-A, diffusely infiltrative margin; n = 14, group 2-B) was the reference standard. Radiomic volume and shape (VS) and other (T2) features were extracted from entire tumor volume and margin, respectively. Twelve radiomics models were generated using four combinations of classifier algorithms (R, SR, LR, LSR) and three different inputs (VS, T2, VS + T2 [VST2] features) to differentiate the three groups. Three radiologists (reader 1, 2, 3) analyzed the marginal infiltration with 6-scale confidence score. STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC) and concordance rate. RESULTS: Averaged AUCs of R, SR, LR, LSR models were 0.438, 0.466, 0.438, 0.466 using VS features, 0.596, 0.584, 0.814, 0.815 using T2 features, and 0.581, 0.587, 0.821, 0.821 using VST2 features, respectively. The LR and LSR models constructed with T2 or VST2 features showed higher AUC and concordance rate compared to radiologists' analysis (AUC; 0.730, 0.675, 0.706, concordance rate; 0.46, 0.43, 0.47 in reader 1, 2, 3). DATA CONCLUSION: Radiomics model constructed with features from tumor margin on T2-weighted Dixon sequence is a promising method for differentiating infiltration degree of STS margin. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Papillary thyroid cancer with Hashimoto's thyroiditis attenuates the tumour aggressiveness through the up-regulation of E-cadherin and TGF-ß expression.

Human papillary thyroid cancer (PTC) is often associated with Hashimoto's thyroiditis (HT), and their coexistence improves the prognosis of PTC. Aim of the study. The objective of our study is to investigate the expression of cadherins and TGF-ß which are regulators in the tumour aggressiveness with metastatic spread in PTC patients and its relationship with HT. The expression of E-cadherin and N-cadherin was measured in thyroid tissues of healthy volunteers and PTC patients with HT (PTC/HT) or without. The E-cadherin expression was also determined in thyroid cancer cells (TPC1, SNU373, SNU790, 8505C, CAL62, and FTC133). Cell migration was measured by wound healing assay. The expression of N-cadherin, ICAM1, and TGF-ß was measured in thyroid tissues and plasma. The E-cadherin expression was significantly increased in PTC/HT patients compared with PTC alone. Meanwhile, the N-cadherin expression was significantly decreased in PTC/HT patients. The E-cadherin expression was only observed in FTC cells, and the overexpression of E-cadherin inhibited cancer cell migration. The TGF-ß expression was significantly increased in PTC/HT patients, and the plasma levels were higher in PTC/HT patients than in PTC alone. The expression of N-cadherin and ICAM-1 was significantly decreased in PTC/HT patients. Our results indicate that the expression of E-cadherin and TGF-ß was higher in PTC/HT patients than in PTC alone. This suggests that the presence of PTC with HT may attenuate the tumour aggressiveness and metastasis through the up-regulation of E-cadherin and TGF-ß expression.