Impact of Tumor Subclassifications for Identifying an Appropriate Surgical Strategy in Patients with Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. The impact of these subclassifications for identifying appropriate surgical strategies remains unclear. PATIENTS AND METHODS: This study included 118 patients with ICC who underwent liver resection. Based on the pathological examination results, the participants were divided into the small duct-type ICC group (n = 64) and large duct-type ICC group (n = 54). The clinicopathological features and postoperative outcomes were compared between the two groups to investigate the impact of subclassification for selecting appropriate surgical strategies. RESULTS: Ten patients in the small duct-type ICC group had synchronous or metachronous hepatocellular carcinoma. The large duct-type ICC group had higher proportions of patients who underwent major hepatectomy, extrahepatic bile duct resection, portal vein resection, and lymph node sampling or dissection than the small duct-type ICC group. The large duct-type ICC group had significantly higher incidences of lymph node metastasis/recurrence and pathological major vessel invasion than the other. The small duct-type ICC group exhibited significantly higher recurrence-free and overall survival rates than the large duct-type ICC group. Further, the large duct-type ICC group had a significantly higher incidence of lymph node metastasis/recurrence than the small duct-type ICC at the perihilar region group. CONCLUSIONS: Suitable surgical strategies may differ between the small and large duct-type ICCs. In patients with large duct-type ICCs, hepatectomy with lymph node dissection and/or biliary reconstruction should be considered, whereas hepatectomy without these advanced procedures can be suggested for patients with small duct-type ICCs.

Radiofrequency ablation in patients with interstitial lung disease and lung neoplasm: a retrospective multicenter study.

PURPOSE: To retrospectively investigate the safety and efficacy of percutaneous radiofrequency ablation (RFA) by analyzing results in patients with lung neoplasm accompanied by interstitial lung disease (ILD) on computed tomography (CT) in a multicenter study. MATERIALS & METHODS: Patients with lung neoplasm accompanied by ILD who underwent RFA between April 2002 and October 2017 at seven institutions were investigated. Technical success rate, and local tumor progression (LTP) of ablated tumors were evaluated. Adverse events including acute exacerbation of ILD were also evaluated. Univariate analyses were performed to identify factors associated with acute exacerbation. RESULTS: Forty-nine patients with 64 lung neoplasm (mean diameter, 22.6 mm; range, 4-58 mm) treated in 66 sessions were included. Usual interstitial pneumonia (UIP) pattern on CT was identified in 23 patients (47%). All patients underwent successful RFA. Acute exacerbations were seen in 5 sessions (8%: 7% with UIP pattern, 8% without) in 5 patients, all occurring on or after 8 days (median, 12 days; range, 8-30 days). Three of those 5 patients died of acute exacerbation. Treatment resulted in mortality after 5% of sessions, representing 6% of patients. Pleural effusion and fever ≥38°C after RFA were identified by univariate analysis (p = 0.0012, p = 0.02, respectively) as significant risk factors for acute exacerbation. The cumulative LTP rate was 43% at 1 year. CONCLUSIONS: RFA appears feasible for patients with lung neoplasm complicated by ILD. Acute exacerbation occurred in 8% of patients with symptoms occurring more than 8 days post-ablation and was associated with a 45% mortality rate.

Promoter methylation levels of microRNA-124 in non-neoplastic rectal mucosa as a potential biomarker for ulcerative colitis-associated colorectal cancer in pediatric-onset patients.

PURPOSE: To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC). METHODS: Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients. RESULTS: Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone (P = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC. CONCLUSION: miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC.

Elucidation of the Tissue Distribution and Host Immunostimulatory Activity of Exogenously Administered Probiotic-Derived Extracellular Vesicles for Immunoadjuvant.

Extracellular vesicles (EVs) are cell-derived nanoparticles that can be used as novel biomaterials. In the development of EVs-based therapeutic systems, it is essential to understand the in vivo fate of exogenously administered EVs and subsequent biological responses mediated by EVs. Although probiotics and microorganisms that modulate the host immune system also secrete EVs, their tissue distribution and biological reactions after administration to the host have not been sufficiently elucidated. In this study, we characterized EVs released from the probiotics Bifidobacterium longum (B-EVs) and Lactobacillus plantarum WCFS1 (L-EVs) in terms of tissue distribution and immune-activating capacity after intravenous and subcutaneous administration in mice. B-EVs and L-EVs exhibited particle sizes of approximately 100-160 nm and negative zeta potentials. These EVs contained peptidoglycan, DNA, and RNA as their cargoes. Intravenously administered B-EVs and L-EVs mainly accumulated in the liver and spleen. Furthermore, liver F4/80 and splenic CD169 macrophages took up the intravenously administered EVs. Subcutaneously administered B-EVs and L-EVs accumulated in the lymph nodes and were mainly located in the B-lymphocyte zone, indicating that exogenously administered probiotic-derived EVs showed a similar biodistribution, irrespective of the EVs-secreting cell type. Evaluation of EVs-mediated immune reactions demonstrated that intravenously administered EVs showed little activation potency. In contrast, subcutaneously administered B-EVs strongly increased the expression of inflammatory cytokine (TNF-α) and co-stimulatory molecules (CD40 and CD80) than L-EVs. These findings indicate that the subcutaneous administration of B-EVs is a useful strategy for the development of novel EVs-based immunotherapies.

Coordination Structure of Samarium Diiodide in a Tetrahydrofuran-Water Mixture.

Chemoselective reductive conversion of organic and inorganic compounds has been developed by the combination of samarium(II) diiodide (SmI2) and water. Despite the extensive previous studies to elucidate the role of water in the reactivity of SmI2, the direct structural data of the reactive Sm2+-water complexes, SmI2(H2O)n, in an organic solvent-water mixture have not been reported experimentally so far. Herein, we performed the structure analysis of the Sm2+-water complex in tetrahydrofuran (THF) in the presence of water by in situ X-ray absorption spectroscopy using high-energy X-rays (Sm K-edge, 46.8 keV). The analysis revealed the dissociation of the Sm2+-I bonds in the presence of ≥ eight equivalents of water in the THF-water mixture. The origin of the peak shift in the UV/visible absorption spectra after the addition of water into SmI2/THF solution was proposed based on electron transitions simulated with time-dependent density-functional-theory calculations using optimized structures in THF or water. The obtained structural information provides the fundamental insights for elucidating the reactivity and chemoselectivity in the Sm2+-water complex system.

Identification of reversed portal flow on 4DCT and of factors contributing to reversed portal flow in patients with liver cirrhosis and portosystemic shunt before interventional radiology procedures.

AIM: Patients with liver cirrhosis and portosystemic shunt occasionally develop reversed portal flow in the portal venous system. The factors contributing to reversed portal flow in these patients remain unclear. The aim of this study was to identify factors contributing to reversed portal flow in patients with portosystemic shunts based on four-dimensional computed tomography (4DCT), which visualized flow dynamics in the portal venous system. METHODS: Data from 34 consecutive patients with portosystemic shunts who had undergone 4DCT before interventional radiology procedures were retrospectively investigated in this study. Uni- and multivariate analyses were performed to identify factors contributing to reversed portal flow. RESULTS: Flow dynamics could be visualized on 4DCT in 32 of the 34 patients. Fifteen patients had forward portal flow; 17 had reversed portal flow. The main portal, splenic, and superior mesenteric veins displayed reversed portal flow in five, 12, and five vessels, respectively. Portosystemic shunt originating from splenic and superior mesenteric veins, worse albumin-bilirubin score, and small main portal vein diameter were significant factors contributing to reversed portal flow in both univariate (p = 0.049, p = 0.027, and p = 0.002) and multivariate (odds ratio [OR] 6.345, p = 0.012; OR 4.279, p = 0.039; and OR 5.516, p = 0.019) analyses. CONCLUSIONS: The reversed portal flow was visualized on 4DCT. Portosystemic shunt originating distant to the liver, worse albumin-bilirubin score, and small diameter of the main portal vein were factors contributing to reversed flow in the portal venous system.

Lymphatic Transport and Immune Activation Effect by Locally Administered Extracellular Vesicles from Saccharomyces cerevisiae as Biocompatible Vaccine Adjuvants.

The yeast strain Saccharomyces cerevisiae is an eukaryotic organism that has been widely used for the production of fermented foods. Most cells secrete extracellular vesicles (EVs), small particles composed of lipid membranes. Elucidating the role of EVs as a new intercellular communication system and developing novel EV-based therapies have attracted the increased attention of researchers. Although recent studies have reported the secretion of EVs from S. cerevisiae, their in vivo fate and subsequent EV-mediated biological responses in the host are unclear. In this study, we characterized both the biodistribution of locally (intradermally and subcutaneously) administered Saccharomyces cerevisiae-derived EVs (S-EVs) and the EV-mediated immune responses to evaluate their potential use as biocompatible vaccine adjuvants. S-EVs were round but heterogeneous in size and contained glucan, DNA, and RNA. Their mean particle sizes and zeta potentials were approximately 177.5 nm and -14.6 mV, respectively. We provided evidence that locally administered S-EVs were delivered to the lymph nodes, mainly reaching the B-cell zone. Measurement of host immune reactions revealed that administration of S-EVs increased the expression of cytokine (tumor necrosis factor (TNF)-α) and costimulatory molecules (CD40, CD80, CD86), which are indicators of immune activation. Especially, subcutaneously injected S-EVs showed potent adjuvanticity, indicating that subcutaneous administration of S-EVs is the desirable approach for achieving effective immune stimulation. These findings will facilitate the development of novel EV-based immunotherapies.

Comparison Between Amide Proton Transfer Magnetic Resonance Imaging Using 3-Dimensional Acquisition and Diffusion-Weighted Imaging for Characterization of Prostate Cancer: A Preliminary Study.

OBJECTIVE: This study aimed to compare diagnostic performance for tumor detection and for assessment of tumor aggressiveness in prostate cancer (PC) between amide proton transfer magnetic resonance imaging (MRI) with 3-dimensional acquisition (3DAPT) and diffusion-weighted imaging. METHODS: The subjects were 23 patients with 27 pathologically proven PCs who underwent 3T multiparametric MRI. With reference to the pathology findings, 2 readers in consensus identified the location of PC on multiparametric MRI and measured APT signal intensity (APT SI [%]) and mean apparent diffusion coefficient (ADC) of the benign region and each PC lesion. RESULTS: The mean ADC showed a significant difference between benign regions and PC lesions (0.74 ± 0.15 vs 1.37 ± 0.21, P < 0.001), whereas APT SI did not ( P = 0.091). Lesion APT SI was significantly higher and lesion ADC was significantly lower in PCs with Gleason group (GG) ≥3 than in PCs with GG ≤2 (3.37 ± 1.30 vs 1.78 ± 0.67, P < 0.001, and 0.71 ± 0.18 vs 0.79 ± 0.10, P = 0.038, respectively). The APT SI was significantly higher in GG3 than in GG1, in GG3 than in GG2, and in GG4 than in GG2 ( P = 0.009, P = 0.001, and P = 0.006, respectively). The area under the curve for separating tumor lesions and benign regions was 0.601 for 3DAPT and 0.983 for ADC ( P < 0.001). The area under the curve for separating tumors with GG ≤2 from tumors with GG ≥3 was 0.912 for 3DAPT and 0.734 for ADC ( P = 0.172). CONCLUSIONS: In patients with PC, it might be preferable to use ADC to discriminate benign from malignant tissue and use APT SI for assessment of tumor aggressiveness.

Pancreaticoduodenectomy with celiac artery resection (PD-CAR) for unresctable locally advanced pancreatic ductal adenocarcinoma.

PURPOSE: Locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) involving the celiac artery (CeA), the common hepatic artery and the gastroduodenal artery (GDA) is considered unresectable. We developed the novel procedure of pancreaticoduodenectomy with celiac artery resection (PD-CAR) for such LA-PDACs. METHODS: From 2015 to 2018, we performed curative pancreatectomy with major arterial resection for 13 LA-PDACs as a clinical study (UMIN000029501). Of those, four patients with pancreatic neck cancer involving the CeA and GDA were candidates for PD-CAR. Prior to surgery, blood flow alterations were performed to unify the blood flow to the liver, stomach, and pancreas, resulting in feeding from the cancer-free artery. During PD-CAR, arterial reconstruction of the unified artery was performed as needed. Based on the records of PD-CAR cases, we retrospectively analyzed the validity of the operation. RESULTS: R0 resection was achieved in all patients. Arterial reconstruction was performed in three patients. In another patient, the hepatic arterial flow was maintained by preserving of the left gastric artery. The mean operative time was 669 min, and the mean blood loss was 1003 ml. Although Clavien-Dindo classification III-IV postoperative morbidities occurred in three patients, no reoperations nor mortalities occurred. Although two patients died of cancer recurrence, one patient survived for 26 months without recurrence (died of cerebral infarction), and another is alive at 76 months without recurrence. CONCLUSION: PD-CAR, which enabled R0 resection and preservation of the residual stomach, pancreas, and spleen, provided acceptable postoperative outcomes.

The effectiveness of simulation-based education combined with peer-assisted learning on clinical performance of first-year medical residents: a case-control study.

BACKGROUND: Simulation-based education and peer-assisted learning (PAL) are both known as useful educational methods. Previous research has reported that combining these two methods are effective for training medical residents in short-term evaluation. This study was aimed to evaluate the middle- to long-term effects of simulation-based education combined with PAL on the performance of medical residents during emergency department duties. METHODS: This study was designed as a case-control study and conducted over three years at Okayama University Hospital in Japan. Postgraduate-year-one medical residents were assigned to three groups: a simulation group that received simulation-based education, a lecture group that received traditional lecture-based education, and a control group that received no such prior trainings. Prior training in emergency department duties using PAL was performed as an educational intervention for the simulation and lecture groups during the clinical orientation period. The residents' medical knowledge was assessed by written examinations before and after the orientation. The performance of residents during their emergency department duties was assessed by self-evaluation questionnaires and objective-assessment checklists, following up with the residents for three months after the orientation period and collecting data on their 1st, 2nd, and 3rd emergency department duties. All the datasets collected were statistically analyzed and compared by their mean values among the three groups. RESULTS: A total of 75 residents were included in the comparative study: 27 in the simulation group, 24 in the lecture group, and 24 in the control group. The simulation and lecture groups obtained significantly higher written examination scores than the control group. From the self-evaluation questionnaires, the simulation group reported significantly higher satisfaction in their prior training than the lecture group. No significant differences were found in the emergency department performance of the residents among the three groups. However, when evaluating the improvement rate of performance over time, all three groups showed improvement in the subjective evaluation, and only the simulation and lecture groups showed improvement in the objective evaluation. CONCLUSION: Simulation-based education combined with PAL is effective in improving the knowledge and satisfaction of medical residents, suggesting the possibility of improving work performance during their emergency department duties.

Deep learning-based screening tool for rotator cuff tears on shoulder radiography.

BACKGROUND: Early diagnosis of rotator cuff tears is essential for appropriate and timely treatment. Although radiography is the most used technique in clinical practice, it is difficult to accurately rule out rotator cuff tears as an initial imaging diagnostic modality. Deep learning-based artificial intelligence has recently been applied in medicine, especially diagnostic imaging. This study aimed to develop a deep learning algorithm as a screening tool for rotator cuff tears based on radiography. METHODS: We used 2803 shoulder radiographs of the true anteroposterior view to develop the deep learning algorithm. Radiographs were labeled 0 and 1 as intact or low-grade partial-thickness rotator cuff tears and high-grade partial or full-thickness rotator cuff tears, respectively. The diagnosis of rotator cuff tears was determined based on arthroscopic findings. The diagnostic performance of the deep learning algorithm was assessed by calculating the area under the curve (AUC), sensitivity, negative predictive value (NPV), and negative likelihood ratio (LR-) of test datasets with a cutoff value of expected high sensitivity determination based on validation datasets. Furthermore, the diagnostic performance for each rotator cuff tear size was evaluated. RESULTS: The AUC, sensitivity, NPV, and LR- with expected high sensitivity determination were 0.82, 84/92 (91.3%), 102/110 (92.7%), and 0.16, respectively. The sensitivity, NPV, and LR- for full-thickness rotator cuff tears were 69/73 (94.5%), 102/106 (96.2%), and 0.10, respectively, while the diagnostic performance for partial-thickness rotator cuff tears was low at 15/19 (78.9%), NPV of 102/106 (96.2%) and LR- of 0.39. CONCLUSIONS: Our algorithm had a high diagnostic performance for full-thickness rotator cuff tears. The deep learning algorithm based on shoulder radiography helps screen rotator cuff tears by setting an appropriate cutoff value. LEVEL OF EVIDENCE: Level III: Diagnostic Study.

An Aqueous Redox Flow Battery Using CO2 as an Active Material with a Homogeneous Ir Catalyst.

For the application of CO2 as an energy storage material, a H2 storage system has been proposed based on the interconversion of CO2 and formic acid (or formate). However, energy losses are inevitable in the conversion of electrical energy to H2 as chemical energy (≈70 % electrical efficiency) and H2 to electrical energy (≈40 % electrical efficiency). To overcome these significant energy losses, we developed a system based on the interconversion of CO2 and formate for the direct storage and generation of electricity. In this paper, we report an aqueous redox flow battery system using homogeneous Ir catalysts with CO2 -formate redox pair. The system exhibited a maximum discharge capacity of 10.5 mAh (1.5 Ah L-1 ), capacity decay of 0.2 % per cycle, and total turnover number of 2550 after 50 cycles. During charging-discharging, in situ fluorescence X-ray absorption fine structure spectroscopy based on an online setup indicated that the active species was in a high valence state of IrIV .

Three-dimensional visualization and quantitative analysis of embryonic and fetal thigh muscles using magnetic resonance and phase-contrast X-ray imaging.

The musculoskeletal system around the human hip joint has acquired a suitable structure for erect bipedal walking. However, little is known about the process of separation and maturation of individual muscles during the prenatal period, when muscle composition is acquired. Understanding the maturation process of the normal musculoskeletal system contributes to elucidating the acquisition of bipedal walking in humans and to predicting normal growth and detecting congenital muscle disorders and anomalies. In this study, we clarify the process of thigh muscle maturation from the embryonic stage to the mid-fetal stage using serial sections, phase-contrast X-ray computed tomography, and magnetic resonance imaging. We also provide a 4D atlas of human thigh muscles between 8 and 23 weeks of gestation. As a result, we first show that muscle separation in the lower thigh tends to progress from the superficial to the deep layers and that all musculoskeletal components are formed by Carnegie Stage 22. Next, we show that femur and muscle volume grow in correlation with crown-rump length. Finally, we show that the anterior, abductor, and posterior muscle groups in the thigh contain a high percentage of monoarticular muscle volume by the end of the embryonic period. This ratio approaches that of adult muscle composition during normal early fetal development and is typical of bipedal walking. This study of fetal muscle composition suggests that preparation for postnatal walking may begin in early fetal period.

Phosphorylated Serine-Modified Polyamidoamine Dendrimer as an Osteoid Surface-Targeting Drug Carrier.

The aim of this study was to develop a polyethylene glycol (PEG)-conjugated third-generation polyamidoamine dendrimer (PAMAM) with phosphorylated serine as an osteoid surface-targeting drug carrier for the treatment of bone diseases. We conjugated PAMAM backbones to l-serine and obtained Ser-PAMAM. Then, phosphoric acid and PEG were covalently bound to the Ser-PAMAM to generate PEGylated phosphorylated Ser-PAMAM (PEG-phosSer-PAMAM). Using osteoblast-like cells (MC3T3-E1 cells) cultured in 3D collagen gels, we showed that phosSer-PAMAM adsorbed both the hydroxyapatite and type I collagen components of the bone matrix. Fourier transform infrared spectroscopy analysis indicated that the phosphoryl side chains of phosSer-PAMAM formed electrostatic interactions and hydrogen bonds with the anionic amino acid residues of type I collagen. Mice were intravenously injected with the foregoing molecules, and a tissue distribution study disclosed that the lower limb bone took up about twice as much 111In-labeled PEG-phosSer-PAMAM as 111In-labeled nonphosphorylated PEG-Ser-PAMAM or unmodified PAMAM. An intrabone distribution experiment showed that fluorescein isothiocyanate (FITC)-labeled PEG-phosSer-PAMAM accumulated on the osteoid surfaces, which is associated with bone pathogenesis such as skeletal dysplasias and osteoporosis to a far greater extent than nonphosphorylated PEG-Ser-PAMAM. Our findings indicated that PEG-phosSer-PAMAM is a promising carrier for efficient drug targeting to osteoid surfaces.

Value of 3-T MR imaging in intraductal papillary mucinous neoplasm with a concomitant invasive carcinoma.

OBJECTIVES: To examine the value of 3-T MRI for evaluating the difference between the pancreatic parenchyma of intraductal papillary mucinous neoplasm with a concomitant invasive carcinoma (IPMN-IC) and the pancreatic parenchyma of patients without an IPMN-IC. METHODS: A total of 132 patients underwent abdominal 3-T MRI. Of the normal pancreatic parenchymal measurements, the pancreas-to-muscle signal intensity ratio in in-phase imaging (SIR-I), SIR in opposed-phase imaging (SIR-O), SIR in T2-weighted imaging (SIR-T2), ADC (×10-3 mm2/s) in DWI, and proton density fat fraction (PDFF [%]) in multi-echo 3D DIXON were calculated. The patients were divided into three groups (normal pancreas group: n = 60, intraductal papillary mucinous neoplasm (IPMN) group: n = 60, IPMN-IC group: n = 12). RESULTS: No significant differences were observed among the three groups in age, sex, body mass index, prevalence of diabetes mellitus, and hemoglobin A1c (p = 0.141 to p = 0.657). In comparisons among the three groups, the PDFF showed a significant difference (p < 0.001), and there were no significant differences among the three groups in SIR-I, SIR-O, SIR-T2, and ADC (p = 0.153 to p = 0.684). The PDFF of the pancreas was significantly higher in the IPMN-IC group than in the normal pancreas group or the IPMN group (p < 0.001 and p < 0.001, respectively), with no significant difference between the normal pancreas group and the IPMN group (p = 0.916). CONCLUSIONS: These observations suggest that the PDFF of the pancreas is associated with the presence of IPMN-IC. KEY POINTS: • The cause and risk factors of IPMN with a concomitant invasive carcinoma have not yet been clarified. • The PDFF of the pancreas was significantly higher in the IPMN-IC group than in the normal pancreas group or the IPMN group. • Pancreatic PDFF may be a potential biomarker for the development of IPMN with a concomitant invasive carcinoma.

Maskless 2-Dimensional Digital Subtraction Angiography Generation Model for Abdominal Vasculature using Deep Learning.

PURPOSE: To develop a deep learning (DL) model to generate synthetic, 2-dimensional subtraction angiograms free of artifacts from native abdominal angiograms. MATERIALS AND METHODS: In this retrospective study, 2-dimensional digital subtraction angiography (2D-DSA) images and native angiograms were consecutively collected from July 2019 to March 2020. Images were divided into motion-free (training, validation, and motion-free test datasets) and motion-artifact (motion-artifact test dataset) sets. A total of 3,185, 393, 383, and 345 images from 87 patients (mean age, 71 years ± 10; 64 men and 23 women) were included in the training, validation, motion-free, and motion-artifact test datasets, respectively. Native angiograms and 2D-DSA image pairs were used to train and validate an image-to-image translation model to generate synthetic DL-based subtraction angiography (DLSA) images. DLSA images were quantitatively evaluated by the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) using the motion-free dataset and were qualitatively evaluated via visual assessments by radiologists with a numerical rating scale using the motion-artifact dataset. RESULTS: The DLSA images showed a mean PSNR (± standard deviation) of 43.05 dB ± 3.65 and mean SSIM of 0.98 ± 0.01, indicating high agreement with the original 2D-DSA images in the motion-free dataset. Qualitative visual evaluation by radiologists of the motion-artifact dataset showed that DLSA images contained fewer motion artifacts than 2D-DSA images. Additionally, DLSA images scored similar to or higher than 2D-DSA images for vascular visualization and clinical usefulness. CONCLUSIONS: The developed DL model generated synthetic, motion-free subtraction images from abdominal angiograms with similar imaging characteristics to 2D-DSA images.

Activation of Host Immune Cells by Probiotic-Derived Extracellular Vesicles via TLR2-Mediated Signaling Pathways.

Since probiotic-derived extracellular vesicles (EVs) are capable of activating innate immunity, they are expected to be useful as novel adjuvants. To elucidate the mechanisms underlying the immunostimulatory effects of EVs released from probiotic cells, we newly investigated the role of Toll-like receptor 2 (TLR2) and immune cell downstream signaling in the generation of proinflammatory cytokines. Isolated Bifidobacterium- and Lactobacillus-derived EVs expressed peptidoglycan, one of the major pathogen-associated molecular patterns. EVs particle diameter were approximately 110-120 nm with a negative-zeta potential. The generation of proinflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in TLR2-expressing mouse macrophage-like RAW264.7 cells and mouse dendritic DC2.4 cells treated with Bifidobacterium- and Lactobacillus-derived EVs decreased after the addition of T2.5, a TLR2 inhibitory antibody. Furthermore, we showed that the signaling pathways of c-Jun-NH2-terminal kinase (JNK)/mitogen-activated protein kinases (MAPK) and nuclear factor-kappaB (NF-κB) were also involved in the production of proinflammatory cytokines from EV-treated immune cells. These results provide valuable information for understanding of the host biological function induced by probiotic-derived EVs, which is helpful for developing an EV-based immunotherapeutic system.

Diffusion-weighted imaging in prostate cancer.

Diffusion-weighted imaging (DWI), a key component in multiparametric MRI (mpMRI), is useful for tumor detection and localization in clinically significant prostate cancer (csPCa). The Prostate Imaging Reporting and Data System versions 2 and 2.1 (PI-RADS v2 and PI-RADS v2.1) emphasize the role of DWI in determining PIRADS Assessment Category in each of the transition and peripheral zones. In addition, several recent studies have demonstrated comparable performance of abbreviated biparametric MRI (bpMRI), which incorporates only T2-weighted imaging and DWI, compared with mpMRI with dynamic contrast-enhanced MRI. Therefore, further optimization of DWI is essential to achieve clinical application of bpMRI for efficient detection of csPC in patients with elevated PSA levels. Although DWI acquisition is routinely performed using single-shot echo-planar imaging, this method suffers from such as susceptibility artifact and anatomic distortion, which remain to be solved. In this review article, we will outline existing problems in standard DWI using the single-shot echo-planar imaging sequence; discuss solutions that employ newly developed imaging techniques, state-of-the-art technologies, and sequences in DWI; and evaluate the current status of quantitative DWI for assessment of tumor aggressiveness in PC.

Clinical application of single-shot echo-planar diffusion-weighted imaging with compressed SENSE in prostate MRI at 3T: preliminary experience.

OBJECTIVES: Image quality (IQ) of diffusion-weighted imaging (DWI) with single-shot echo-planar imaging (ssEPI) suffers from low signal-to-noise ratio (SNR) in high b-value acquisitions. Compressed SENSE (C-SENSE), which combines SENSE with compressed sensing, enables SNR to be improved by reducing noise. The aim of this study was to compare IQ and prostate cancer (PC) detectability between DWI with ssEPI using SENSE (EPIS) and using C-SENSE (EPICS). MATERIALS AND METHODS: Twenty-five patients with pathologically proven PC underwent multi-parametric magnetic resonance imaging at 3T. DW images acquired with EPIS and EPICS were assessed for the following: lesion conspicuity (LC), SNR, contrast-to-noise ratio (CNR), mean and standard deviation (SD) of apparent diffusion coefficient (ADC) of lesion (lADCm and lADCsd), coefficient of variation of lesion ADC (lADCcv), and mean ADC of benign prostate (bADCm). RESULTS: LC were comparable between EPIS and EPICS (p > 0.050), and SNR and CNR were significantly higher in EPICS than EPIS (p = 0.001 and p < 0.001). In both EPIS and EPICS, lADCm was significantly lower than bADCm (p < 0.001). In addition, lADCcv was significantly lower in EPICS than in EPIS (p < 0.001). CONCLUSION: Compared with EPIS, EPICS has improved IQ and comparable diagnostic performance in PC.

Simultaneous Determination of Active Pharmaceutical Ingredients and Water-Soluble Polymers: Analysis of Dissolution Profiles from Sustained-Release Formulations and Mechanisms Involved.

The dissolution behaviors of base excipients from sustained-release formulations have been investigated using various methodologies. However, the dissolution of polymers has not been fully evaluated because differences between formulations are still verified only by the release of active pharmaceutical ingredients (APIs). In our previous study, we proposed a quick and simultaneous analysis of dissolved APIs and water-soluble polymers by ultra HPLC using charged aerosol and photodiode array detectors. The purpose of this study was to verify whether the analysis system could be adapted to other water-soluble polymers. Dissolution tests were conducted using matrix model tablets prepared from three polymers and three APIs (propranolol, ranitidine, and cilostazol) with different solubilities. The dissolution profiles of the polymers and APIs were determined using the proposed analysis system and compared. The results clarified differences in the dissolution behaviors of the APIs and polymers. The polymers, especially hydroxypropyl cellulose, exhibited the dissolution properties characteristic of each model formulation. Propranolol and ranitidine showed the diffusion type, while cilostazol showed the erosion type release mechanism due to their different solubilities. The release of cilostazol was delayed in all models compared to the polymer, which may be due to the aggregation of cilostazol in the gel layer. This analytical method can be used to study the dissolution behavior (diffusion or erosion) of APIs from matrix tablets containing various polymers. This method will provide useful information on release control, which will make it easier and more efficient to design appropriate formulations and analyze the release mechanisms.