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Purpose: To retrospectively evaluate the diagnostic potential of magnetic resonance imaging (MRI)-based features and radiomics analysis (RA)-based features for discriminating ovarian clear cell carcinoma (CCC) from endometrioid carcinoma (EC)., Materials and Methods: Thirty-five patients with 40 ECs and 42 patients with 43 CCCs who underwent pretherapeutic MRI examinations between 2011 and 2022 were enrolled. MRI-based features of the two groups were compared. RA-based features were extracted from the whole tumor volume on T2-weighted images (T2WI), contrast-enhanced T1-weighted images (cT1WI), and apparent diffusion coefficient (ADC) maps. The least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation method was performed to select features. Logistic regression analysis was conducted to construct the discriminating models. Receiver operating characteristic curve (ROC) analyses were performed to predict CCC., Results: Four features with the highest absolute value of the LASSO algorithm were selected for the MRI-based, RA-based, and combined models: the ADC value, absence of thickening of the uterine endometrium, absence of peritoneal dissemination, and growth pattern of the solid component for the MRI-based model; Gray-Level Run Length Matrix (GLRLM) Long Run Low Gray-Level Emphasis (LRLGLE) on T2WI, spherical disproportion and Gray-Level Size Zone Matrix (GLSZM), Large Zone High Gray-Level Emphasis (LZHGE) on cT1WI, and GLSZM Normalized Gray-Level Nonuniformity (NGLN) on ADC map for the RA-based model; and the ADC value, spherical disproportion and GLSZM_LZHGE on cT1WI, and GLSZM_NGLN on ADC map for the combined model. Area under the ROC curves of those models were 0.895, 0.910, and 0.956. The diagnostic performance of the combined model was significantly superior (p = 0.02) to that of the MRI-based model. No significant differences were observed between the combined and RA-based models., Conclusion: Conventional MRI-based analysis can effectively distinguish CCC from EC. The combination of RA-based features with MRI-based features may assist in differentiating between the two diseases., (© 2024. The Author(s).)

Purpose: This study aimed to characterize the clinical and imaging findings of intraductal oncocytic papillary neoplasm of the pancreas (IOPN-P) compared to those of intraductal papillary mucinous adenoma/carcinoma (IPMA/IPMC)., Methods: This multi-institutional retrospective study reviewed the clinical, imaging, and pathological findings of 21 patients with pathologically proven IOPN-P. Twenty-one computed tomography (CT) and magnetic resonance imaging, and seven 18 F-fluorodeoxyglucose (FDG)-positron emission tomography were performed before surgery. The following findings were evaluated: preoperative blood test results, lesion size and location, pancreatic duct diameter, contrast-enhancement effect, bile duct and peripancreatic invasion, maximum standardized uptake (SUVmax) value, and pathological stromal invasion., Results: Serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9) levels were significantly higher in the IPMN/IPMC group than in the IOPN-P group. Except in one patient, IOPN-P showed multifocal cystic lesions with solid components or a tumor in the main pancreatic duct (MPD) with dilatation. IOPN-P had a higher frequency of solid parts and a lower frequency of downstream MPD dilatation than IPMA. IPMC showed smaller overall cyst size, more radiological peripancreatic invasion, and worse recurrence-free and overall survival than IOPN-P. The average SUVmax value of IOPN-P was 7.5. Pathologically, 17 of the 21 IOPN-Ps had a malignant component, and six showed stromal invasion., Conclusion: IOPN-P shows cystic-solid lesions similar to IPMC but has lower serum CEA and CA19-9 levels, larger overall cyst size, lower frequency of peripancreatic invasion, and more favorable prognosis than IPMC. Moreover, the high FDG uptake by IOPN-Ps may be a characteristic finding of this study., (© 2023. The Author(s).)

Entamoeba histolytica is distributed throughout the world. Invasive amebiasis affects millions of people globally, and the associated complications cause 40,000-100,000 deaths per year. In countries where fecal-oral transmission is unusual, amebic colitis is not common, and the infection may be seen in travelers to and emigrants from endemic areas. Without adequate treatment, amebic colitis may develop into fulminant and become rapidly fatal. With the current increase in global mobility, amebic colitis should be suspected even in patients not in the endemic areas. CT plays an important role in the diagnosis of amebic colitis by demonstrating the presence of colitis with the typical involvement of the cecum and rectum. Pathological features of atypical involvement are also demonstrated. Since preoperative diagnosis can reduce the mortality associated with necrotizing colitis, radiologists need to recognize the typical as well as atypical CT findings of amebic colitis. Considering this requirement, this paper aims to describe the histopathologic features of amebic colitis and to illustrate the spectrum of corresponding CT findings.

Purpose: To retrospectively evaluate the utility of fusion images of pre- and post-ablation hepatobiliary phase (HBP) series to assess the ablation margins after radiofrequency ablation (RFA) of hepatocellular carcinomas (HCCs). Additionally, to identify factors indicative of an adequate ablation margin and predictors of local tumor progression (LTP)., Methods: Fifty-nine HCCs in 29 patients were treated by RFA and followed-up for > 1 year (mean 37.9 months). Fusion images of pre- and post-ablation HBP series were created using a non-rigid registration and manual correlation. The ablation margin appearance was classified as ablation margin + (ablation margin completely surrounding the tumor), ablation margin-zero (a partially discontinuous ablation margin without protrusion of HCC), ablation margin-(a partially discontinuous ablation margin with protrusion of HCC), and indeterminate (index tumor was not visible). The minimal ablation margin was measured, and clinical factors were examined to identify other risk factors for LTP., Results: LTP was observed at follow-up in 12 tumors. The mean minimal ablation margin was 3.6 mm. Multivariate analysis revealed that the ablation margin status was the only significant factor (p = 0.028). The cumulative LTP rates (3.3%, 3.3%, and 3.3% at 1, 2, and 3 years, respectively) in 30 ablation margin + nodules were significantly lower (p = 0.006) than those (20.0%, 28.0%, and 32.2% at 1, 2, and 3 years, respectively) in 25 ablation margin-zero nodules., Conclusions: Fusion images enable an early assessment of the ablation efficacy in the majority of HCCs. The ablation margin status is a significant factor for LTP.

Intracystic papillary neoplasm (ICPN) of gallbladder is a comparatively new concept and is described as pre-malignant lesions in Nakanuma et al. (In: Bosman et al. (eds) WHO Classification of Tumours of the Digestive System, World Health Organization of Tumours, IARC, Lyon, 2010). ICPN with high-grade intraepithelial neoplasia is understood to include intraepithelial carcinoma or noninvasive carcinoma. And lesions with invasive cancer components are classified as ICPN with an associated invasive carcinoma [1]. According to Adsay et al., more than half of patients diagnosed with ICPN have invasive cancer components (Adsay et al., Am J Surg Pathol 36:1279-1301, 2012).Polypoid masses in the gallbladder including benign, malignant, and non-neoplastic lesions have been called gallbladder polyps, and ICPN is also a polypoid lesion in the gallbladder. However, it is difficult to differentiate between them. In the literature, it is said that the possibility of malignancy is high in lesions exceeding 1 cm (Terzi et al., Surgery 127:622-627, 2000). And there are few reports on characteristic imaging findings of ICPN.We have experienced three cases (two females and one male) of ICPN and report our imaging findings. Contrast-enhanced computed tomography revealed large papillary polypoid lesions approximately 2-4 cm in size in the gallbladder. Findings suggestive of deformation of the gallbladder wall and extrinsic progression were absent in all cases. T2-weighted magnetic resonance imaging revealed intense signals and diffusion-weighted imaging showed high intensity. Expanding of the gallbladder was seen in case 1, and a tumor stalk-like appearance was seen in the papillary mass in cases 2 and 3. Surgery was performed in all three cases and ICPN was diagnosed pathologically. The cancer was localized to the mucosa, with no infiltration of surrounding tissue in all three cases.

Purpose: To evaluate the usefulness of computed tomographic (CT) features for identifying acute torsion of uterine subserosal leiomyoma (USL)., Subjects and Methods: We analyzed contrast-enhanced CT examinations of 7 USLs with torsion and 44 USLs without torsion. Two radiologists evaluated the CT features, which consisted of poor contrast enhancement inside the USL, thin rim enhancement around the USL, calcification within the USL, a beak sign between the uterus and USL, fan-shaped poor contrast enhancement in the uterus area adjacent to the USL (dark fan sign), and ascites. We analyzed the frequencies of these CT features in the USLs with versus without torsion using Fisher's exact test., Results: The respective frequencies of CT features in USLs with and without torsion were as follows: poor contrast enhancement, 86 and 5% (P = 0.001); thin rim enhancement, 71 and 9% (P = 0.001); calcification, 29 and 18% (P = 0.61); beak sign, 57 and 86% (P = 0.10); dark fan sign, 57 and 0% (P = 0.001); and ascites, 100 and 20% (P = 0.01)., Conclusions: The CT features of poor contrast enhancement, thin rim enhancement, and dark fan sign are valuable for identifying acute torsion of USL.

Purpose: To retrospectively determine whether hepatobiliary phase (HBP) sequence outperforms unenhanced T1-weighted imaging (uT1wI) in distinguishing the ablation margin (AM) from hepatocellular carcinoma (HCC) 24 h after thermoablation., Material and Methods: Ninety-one patients [mean age, 65.7 years; 68 M/23F] with 138 HCCs (>6 months follow-up) underwent pre- and postablation gadoxetate disodium-enhanced MRI. AM showed a hyperintense middle zone (MZ) surrounding central hypo- or hyperintense HCCs on uT1wI, and an intermediate-intense MZ encompassing central hypo- or hyperintense HCCs during HBP. The visible AM was defined as persistent MZ around HCCs, which were demarcated from MZ, or peripherally band encompassing MZ, which were not demarcated from HCC. The indefinite AM was defined as no demarcating HCCs from MZ. The ability to distinguish AM from HCC was classified as visible or indefinite on axial (ax)-uT1wI, ax-HBP, coronal (cor)-HBP, and combined all images. To investigate the AM visibility during HBP, significance of differences upon comparison of ax-uT1wI with combined images was analyzed. Preablation liver-tumor contrast ratio (LTCR) on ax-uT1wI and ax-HBP sequence is compared between the visible and indefinite AM., Results: The McNemar test demonstrated a significant increase (p < 0.05) in visible AM from ax-uT1wI (60), to ax-HBP (70), cor-HBP (79), and combined images (83). TLCR with visible AM was significantly higher than that with indefinite AM on ax-uT1wI (0.4 vs. 0.2, p = 0.001) and ax-HBP sequence (0.9 vs. 0.6, p = 0.004)., Conclusions: HBP sequence might have higher feasibility to distinguish AM from tumor than ax-uT1wI. The TLCR value in visible AM was higher than that in indefinite AM on both ax-uT1wI and ax-HBP sequences.

Key Message: The first Good Manufacturing Practices production of a purification-free rice-based oral cholera vaccine (MucoRice-CTB) from transgenic plants in a closed cultivation system yielded a product meeting regulatory requirements. Despite our knowledge of their advantages, plant-based vaccines remain unavailable for human use in both developing and industrialized countries. A leading, practical obstacle to their widespread use is producing plant-based vaccines that meet governmental regulatory requirements. Here, we report the first production according to current Good Manufacturing Practices of a rice-based vaccine, the cholera vaccine MucoRice-CTB, at an academic institution. To this end, we established specifications and methods for the master seed bank (MSB) of MucoRice-CTB, which was previously generated as a selection-marker-free line, evaluated its propagation, and given that the stored seeds must be renewed periodically. The production of MucoRice-CTB incorporated a closed hydroponic system for cultivating the transgenic plants, to minimize variations in expression and quality during vaccine manufacture. This type of molecular farming factory can be operated year-round, generating three harvests annually, and is cost- and production-effective. Rice was polished to a ratio of 95 % and then powdered to produce the MucoRice-CTB drug substance, and the identity, potency, and safety of the MucoRice-CTB product met pre-established release requirements. The formulation of MucoRice-CTB made by fine-powdering of drug substance and packaged in an aluminum pouch is being evaluated in a physician-initiated phase I study.

Key Message: RNAi-mediated suppression of the endogenous storage proteins in MucoRice-CTB-RNAi seeds affects not only the levels of overexpressed CTB and RAG2 allergen, but also the localization of CTB and RAG2. A purification-free rice-based oral cholera vaccine (MucoRice-CTB) was previously developed by our laboratories using a cholera toxin B-subunit (CTB) overexpression system. Recently, an advanced version of MucoRice-CTB was developed (MucoRice-CTB-RNAi) through the use of RNAi to suppress the production of the endogenous storage proteins 13-kDa prolamin and glutelin, so as to increase CTB expression. The level of the α-amylase/trypsin inhibitor-like protein RAG2 (a major rice allergen) was reduced in MucoRice-CTB-RNAi seeds in comparison with wild-type (WT) rice. To investigate whether RNAi-mediated suppression of storage proteins affects the localization of overexpressed CTB and major rice allergens, we generated an RNAi line without CTB (MucoRice-RNAi) and investigated gene expression, and protein production and localization of two storage proteins, CTB, and five major allergens in MucoRice-CTB, MucoRice-CTB-RNAi, MucoRice-RNAi, and WT rice. In all lines, glyoxalase I was detected in the cytoplasm, and 52- and 63-kDa globulin-like proteins were found in the aleurone particles. In WT, RAG2 and 19-kDa globulin were localized mainly in protein bodies II (PB-II) of the endosperm cells. Knockdown of glutelin A led to a partial destruction of PB-II and was accompanied by RAG2 relocation to the plasma membrane/cell wall and cytoplasm. In MucoRice-CTB, CTB was localized in the cytoplasm and PB-II. In MucoRice-CTB-RNAi, CTB was produced at a level six times that in MucoRice-CTB and was localized, similar to RAG2, in the plasma membrane/cell wall and cytoplasm. Our findings indicate that the relocation of CTB in MucoRice-CTB-RNAi may contribute to down-regulation of RAG2.

In order to obtain the full spectrum from 400 to 800 nm of each pixel of a microscopic image, a unique spectro-imaging system was developed using an image slicer. The image slicer is composed of 100 photo fibers which are arranged in a matrix of 10 x 10 at the entrance and 100 x 1 at the exit. A line of this 100 signals is passed through a glism and projected onto a CCD. This system was applied to the fluorescent imaging of bio-cells. One of the demonstrative examples was simultaneous measurements of the Ca2+ concentration and the pH using of respective fluorescent probes. An electric signal was applied to BY-2 protoplasts and the fluorescent spectrum from 500 nm to 800 nm was measured every 5 s. The spectrum of the BY-2 protoplasts changed in response to the electric signal and the Ca2+ concentration, and the pH changes could be monitored. The wavelength resolution was satisfactory, but the space resolution was still rough in comparison with the usual microscopic systems. Notwithstanding these conditions, we could obtain discrete data from more than several tens of sites in a single-cell or a chain of several cells.

Using microdialysis, we studied brain extracellular fluid (ECF) amino acid metabolism in rats with experimentally induced hyperammonemia and regional elevation of brain ECF ammonia levels. The total brain ECF amino acid level was increased by an elevation of the blood ammonia level. Hyperammonemia elevated brain ECF aromatic amino acids and reduced arterial blood branched chain amino acids. When rats with hyperammonemia were intravenously administered norleucine, the brain ECF norleucine level rose markedly, suggesting increased permeability of the blood-brain barrier. When rats with hyperammonemia were infused with a branched chain amino acid-rich preparation, the elevated brain ECF aromatic amino acids level was not suppressed. Following local intracerebral ammonia infusion, only glutamate levels showed a marked elevation. These results suggest that impairment of the blood-brain barrier related to hyperammonemia increases the inflow of low molecular weight substances including amino acids. Furthermore, the ammonia-induced increase of glutamate in the cerebral ECF suggests that high ammonia levels may increase the excitability of the brain. Thus, ammonia may serve as a key factor in the onset of hepatic encephalopathy.

Saponin-permeabilization (30 micrograms/ml) of the platelet plasma membrane, which enables access of added compounds to mitochondrial overt carnitine palmitoyltransferase (CPT I), was applied to allow the rapid determination of CPT I activity in situ. The effects of diabetes and short-term incubation with insulin in vitro on the kinetic parameters and malonyl-CoA sensitivity of CPT I were also studied in rat platelets. CPT I exhibited ordinary Michaelis-Menten kinetics when platelets were incubated with palmitoyl-CoA. Malonyl-CoA showed an I50 (concentration giving 50% inhibition of CPT activity) of 0.92 +/- 0.11 microM in permeabilized platelets. Platelets obtained from diabetic rats (induced by streptozotocin injection) exhibited an increased Vmax and I50 for malonyl-CoA, and an unaltered Km for palmitoyl-CoA. In contrast, preincubation of platelets prepared from both fed control rats and diabetic rats with insulin (100 and 150 microU/ml) led to a decrease in enzyme activity when assayed with 75 microM palmitoyl-CoA and 0.5 mM L-carnitine as substrates. These in vivo and in vitro results suggested that insulin directly modulated rat platelet CPT I activity, as it does in the liver.