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Complementary structural characterization methods are useful for studying the hierarchical cellular morphology of polymer foams. In this study, we employed scanning electron microscopy (SEM) and X-ray micro-computed tomography (micro-CT) to characterize the hierarchical cellular morphology of poly(methyl methacrylate) (PMMA) and polystyrene (PS) foams. The polymer foams were prepared using pure CO2 gas and CO2–chlorodifluoromethane (HCFC-22) gas mixtures as blowing agents. Depending on the type of polymer and HCFC-22 concentration, hierarchical cellular structures consisting of nanocells, microcells, and macrocells were obtained. The size distribution of the nanocells was determined by high-magnification SEM, while the size, shape, and spatial distribution of the microcells and macrocells in three dimensions were determined by micro-CT. Moreover, a well-designed micro-CT experiment enabled a brightness comparison between the foams and relative local density mapping of the foams based on the brightness. The results clearly showed the formation of a dense skin layer at the air interface of both PMMA and PS foams and dense matrix around the large macrocells in the PMMA foams. Thus, combining SEM and micro-CT provides a deeper understanding of the formation mechanism of the hierarchical cellular structure of polymer foams.

We developed a flow microreaction system automated by a LabVIEW-based program enabling a control of flow rates of four pumps, an in-line UV–visible spectroscopic monitoring, and a process data logging including the pump pressures. The system was applied to the synthesis of gold nanoparticles (NPs) by a reduction of hydrogen tetrachloroaurate (III) (HAuCl4) with sodium tetrahydroborate (NaBH4) in the presence of trisodium citrate (Na3C6H5O7). Concentrations of the three reagents were controlled by changing the flow rates and were optimized so that the spectrum of the NPs gave higher peak at shorter wavelength. A gradual change in the concentrations from the dilute condition according to decision-tree algorithm as well as a careful monitoring of the pump pressures were shown to be effective for the optimization without clogging of the particles in the reactor.

Abstract Random forest regression was applied to optimize the melt-blending process of polyphenylene sulfide (PPS) with poly(ethylene-glycidyl methacrylate-methyl acrylate) (E-GMA-MA) elastomer to improve the Charpy impact strength. A training dataset was constructed using four elastomers with different GMA and MA contents by varying the elastomer content up to 20 wt% and the screw rotation speed of the extruder up to 5000 rpm at a fixed barrel temperature of 300 °C. Besides the controlled parameters, the following measured parameters were incorporated into the descriptors for the regression: motor torque, polymer pressure, and polymer temperatures monitored by infrared-ray thermometers installed at four positions (T1 to T4) as well as the melt viscosity and elastomer particle diameter of the product. The regression without prior knowledge revealed that the polymer temperature T1 just after the first kneading block is an important parameter next to the elastomer content. High impact strength required high elastomer content and T1 below 320 °C. The polymer temperature T1 was much higher than the barrel temperature and increased with the screw speed due to the heat of shear. The overheating caused thermal degradation, leading to a decrease in the melt viscosity and an increase in the particle diameter at high screw speed. We thus reduced the barrel temperature to keep T1 around 310 °C. This increased the impact strength from 58.6 kJ m−2 as the maximum in the training dataset to 65.3 and 69.0 kJ m−2 at elastomer contents of 20 and 30 wt%, respectively.

Abstract The Fukushima-Daiichi Nuclear Power Plant (FNPP) accident in March of 2011 released substantial amounts of radionuclides into the environment. We collected 4,957 deciduous teeth formed in children before the Fukushima accident to obtain precise control data for teeth formed after the accident. Radioactivity was measured using imaging plates (IP) and epidemiologically assessed using multivariate regression analysis. Additionally, we measured 90Sr, 137Cs, and natural radionuclides which might be present in teeth. Epidemiological studies of IP showed that the amount of radioactivity in teeth from Fukushima prefecture was similar to that from reference prefectures. We found that artificial radionuclides of 90Sr and 137Cs, which were believed to have originated from past nuclear disasters, and natural radionuclides including 40 K and daughter nuclides in the 238U and 232Th series contributed to the generation of radioactivity in teeth. We also found no evidence to suggest that radionuclides originating from the FNPP accident significantly contaminated pre-existing teeth. This is the first large-scale investigation of radioactivity and radionuclides in teeth. The present findings will be indispensable for future studies of teeth formed after the FNPP accident, which will fall out over the next several years and might be more contaminated with radionuclides.

A new flexible thermal insulation sheet, a composite of silica aerogel with polypropylene (PP) foam, has been developed. Even though a large volume ratio of silica aerogel (97%) was included, the composite showed high flexibility. Thermal conductivity of the composite was 0.016 W/(m⋅K) at 298 K, which is as low as silica aerogel monolith. Silica aerogel flaking, which has been a problem in practical applications, is very low in this composite due to skin layers of the polymer-foam composite. A supercritical drying process for rolled sheets of the material for large-scale production is also described. Simulations of extraction of 2-propanol from a silica alcogel revealed that rolled composite sheets with small spaces between the sheet composite are able to dry in a reasonable extraction time. These findings led to effective on production of this material on a pilot industrial scale.

A novel protein, soritesidine (SOR) with potent toxicity was isolated from the marine sponge Spongosorites sp. SOR exhibited wide range of toxicities over various organisms and cells including brine shrimp (Artemia salina) larvae, sea hare (Aplysia kurodai) eggs, mice, and cultured mammalian cells. Toxicities of SOR were extraordinary potent. It killed mice at 5 ng/mouse after intracerebroventricular (i.c.v.) injection, and brine shrimp and at 0.34 µg/mL. Cytotoxicity for cultured mammalian cancer cell lines against HeLa and L1210 cells were determined to be 0.062 and 12.11 ng/mL, respectively. The SOR-containing fraction cleaved plasmid DNA in a metal ion dependent manner showing genotoxicity of SOR. Purified SOR exhibited molecular weight of 108.7 kDa in MALDI-TOF MS data and isoelectric point of approximately 4.5. N-terminal amino acid sequence up to the 25th residue was determined by Edman degradation. Internal amino acid sequences for fifteen peptides isolated from the enzyme digest of SOR were also determined. None of those amino acid sequences showed similarity to existing proteins, suggesting that SOR is a new proteinous toxin.

Study Design. Burst strength study in porcine dural models and functional and histological study in rat dural models. Objective. This study aimed to investigate the sealing strength and biocompatibility of Alaska pollock-derived gelatin (ApGltn) and fibrin sealants in disrupted dural injuries. Summary of Background Data. Disruption of the dura mater occurs during spine surgery, leading to cerebrospinal fluid leakage. Fibrin sealant is usually applied to ruptured sites; however, it lacks sealing strength. A novel biocompatible sealant composed of ApGltn was recently demonstrated to have good burst strength and biocompatibility in the porcine aorta. Methods. Ten porcine dura maters with central holes were covered with ApGltn and fibrin sealants (five samples per group). The maximum burst strength of each sealant was measured, and histological examination was performed after burst testing. Twenty-seven dura maters of male Wistar rats were used for functional and histopathological evaluations. The rats were treated with three surgical interventions: defect + ApGltn sealant; defect + fibrin sealant; defect alone (nine rats per group). Macroscopic confirmation of the sealant, hindlimb motor function analysis, and histopathological examination were performed at two, four, and eight weeks after the procedure. Results. The maximum burst strength of the ApGltn sealant was ~4.4 times higher than that of the fibrin sealant (68.1 ± 12.1 vs. 15.6 ± 8.7 mmHg; P< 0.001). Histological examination confirmed that the ApGltn sealant showed tight adhesion to the dural surface, whereas a gap was observed between the fibrin sealant and the dura mater. In the rat model, the ApGltn sealant resulted in spinal function and dural histological findings similar to those of the fibrin sealant. Conclusion. The ApGltn sealant had a higher sealing strength than, and comparable effect on dura regeneration with, the fibrin sealant. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Aim In recent years, there has been a rise in cryptogenic hepatocellular carcinoma (c‐HCC) cases in Japan, posing a detection challenge due to an unknown etiology. This study aims to enhance diagnostic strategies for c‐HCC by analyzing its characteristics and exploring current opportunities for detection. Methods A retrospective study was conducted from April 2012 to March 2022, enrolling 372 newly diagnosed hepatocellular carcinoma (HCC) patients. Excluding cases associated with hepatitis viral infection, alcoholic liver disease, non‐alcoholic fatty liver disease/steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and congestive hepatopathy, the study specifically focused on genuine c‐HCC. The analysis delved into the characteristics, detection opportunities, and survival outcomes associated with c‐HCC. Results Among the non‐viral HCC cases, 55 patients (29.3%) (34 men and 21 women) were diagnosed with c‐HCC, making it the second‐highest etiology. Notably, individuals with c‐HCC, typically aged 60 and above (median age 76.0), exhibited a women predominance and presented with larger tumors (4.5 cm vs. 2.5 cm), correlating with a poorer prognosis. Cirrhosis was notably absent in most c‐HCC cases (72.7%), and more than half (56.4%) did not have diabetes mellitus (DM). Diagnostic pathways for c‐HCC primarily involved incidental imaging (47%) and symptoms (24%). Within the cohort of c‐HCC, the prognosis for symptomatic cases is notably unfavorable compared to other cases [median survival time 19.0 (7.0–45.0) months vs. 47.0 (29.0–76.0) months, p = 0.029]. In the multivariate regression analysis, age and women emerged as independent factors associated with c‐HCC. Rather than a significant increase in women, there is a narrowing gender gap. Conclusion Patients with c‐HCC were predominantly elderly, without cirrhosis or diabetes, and exhibited minimal gender differences. Detection often occurred incidentally through abdominal imaging. Considering the limitations of conventional surveillance, it seems reasonable to propose that abdominal imaging be included in cancer screening, particularly for individuals aged 60 and older. Trial Registration 1610A127

Abstract Variations in color and texture of histopathology images are caused by differences in staining conditions and imaging devices between hospitals. These biases decrease the robustness of machine learning models exposed to out-of-domain data. To address this issue, we introduce a comprehensive histopathology image dataset named PathoLogy Images of Scanners and Mobile phones (PLISM). The dataset consisted of 46 human tissue types stained using 13 hematoxylin and eosin conditions and captured using 13 imaging devices. Precisely aligned image patches from different domains allowed for an accurate evaluation of color and texture properties in each domain. Variation in PLISM was assessed and found to be significantly diverse across various domains, particularly between whole-slide images and smartphones. Furthermore, we assessed the improvement in domain shift using a convolutional neural network pre-trained on PLISM. PLISM is a valuable resource that facilitates the precise evaluation of domain shifts in digital pathology and makes significant contributions towards the development of robust machine learning models that can effectively address challenges of domain shift in histological image analysis.

Summary: The stomach is an important digestive organ with various biological functions. However, because of the complexity of its cellular and glandular composition, its precise cellular biology has yet to be elucidated. In this study, we conducted single-cell RNA sequencing (scRNA-seq) and subcellular-level spatial transcriptomics analysis of the human stomach and constructed the largest dataset to date: a stomach encyclopedia. This dataset consists of approximately 380,000 cells from scRNA-seq and the spatial transcriptome, enabling integrated analyses of transcriptional and spatial information of gastric and metaplastic cells. This analysis identified LEFTY1 as an uncharacterized stem cell marker, which was confirmed through lineage tracing analysis. A wide variety of cell-cell interactions between epithelial and stromal cells, including PDGFRA+BMP4+WNT5A+ fibroblasts, was highlighted in the developmental switch of intestinal metaplasia. Our extensive dataset will function as a fundamental resource in investigations of the stomach, including studies of development, aging, and carcinogenesis.

Jaundice is caused by excess circulating bilirubin, known as hyperbilirubinemia. This symptom is sometimes caused by a critical hepatobiliary disorder, and is generally identified as yellowish sclera when bilirubin levels increase more than 3 mg/dL. It is difficult to identify jaundice accurately, especially via telemedicine. This study aimed to identify and quantify jaundice by trans-conjunctiva optical imaging. Patients with jaundice (total bilirubin ≥3 mg/dL) and normal control subjects (total bilirubin n = 10), chronic hepatitis or cirrhosis (n = 6), pancreatic cancer (n = 4), acute liver failure (n = 2), cholelithiasis or cholangitis (n = 2), acute pancreatitis (n = 1), and Gilbert’s syndrome (n = 1). The maximum hue degree (MHD) optimal cutoff to identify jaundice was 40.8 (sensitivity 81% and specificity 80%), and the AUROC was 0.842. The MHD was moderately correlated to total serum bilirubin (TSB) levels (rS = 0.528, p < 0.001). TSB level (≥5 mg/dL) can be estimated by the formula 21.1603 − 0.7371 × 56.3−MHD2. In conclusion, the ABHB-based MHD of conjunctiva imaging identified jaundice using an ordinary smartphone without any specific attachments and deep learning. This novel technology could be a helpful diagnostic tool in telemedicine or self-medication.

Pathological examination by endoscopic ultrasound–fine needle aspiration is not possible in approximately 10% of pancreatic tumor cases. Pancreatic juice cytology (PJC) is considered an alternative diagnostic method. However, its diagnostic capability is insufficient, and PJC has been repeatedly redevised. Serial pancreatic juice aspiration cytological examination (SPACE) and secretin-loaded PJC (S-PJC) have been recently introduced as alternative diagnostic methods. This study aimed to determine the diagnostic capacity and safety of SPACE and S-PJC using a propensity score-matched analysis. The sensitivity, specificity, and accuracy were 75.0%, 100%, and 92.3% for S-PJC, respectively, and 71.4%, 100%, and 92.3% for SPACE, respectively, meaning that there was no significant difference between the groups. Four patients (15.4%) each in the S-PJC and SPACE groups experienced complications, including postendoscopic retrograde cholangiopancreatography, pancreatitis, and cholangitis. Overall, there was no difference in efficacy and safety between the SPACE and S-PJC groups.

A flow-type cell was developed for measuring Compton scattering spectra of heat-sensitive aqueous solution. Compton scattering spectra of water and ethanol were measured in the region from ambient conditions to 623 K and 20 MPa. Compton profiles derived from measurement with the flow-type cell were comparable with those in the literature. Results obtained from the flow-type cell showed that delocalization of electronic charge density of water and ethanol at high temperatures occurred. Delocalization of the electronic charge density of ethanol was greater than that of water at high temperature, which is consistent with the prior works that use proton NMR chemical shifts to describe hydrogen bonding. [ABSTRACT FROM AUTHOR]

Summary: The patient-derived xenograft (PDX) model is a versatile tool used to study the tumor microenvironment (TME). However, limited studies have described multi-tumor PDX screening strategies to detect hub regulators during cancer-stroma interaction. Transcriptomes of cancer (human) and stroma (mouse) components of 70 PDX samples comprising 9 distinctive tumor types were analyzed in this study. PDX models recapitulated the original tumors' features, including tumor composition and putative signaling. Particularly, kidney renal clear cell carcinoma (KIRC) stood out, with altered hypoxia-related pathways and a high proportion of endothelial cells in the TME. Furthermore, an integrated analysis conducted to predict paracrine effectors in the KIRC cancer-to-stroma communication detected well-established soluble factors responsible for the hypoxia-related reaction and the so-far unestablished soluble factor, apelin (APLN). Subsequent experiments also supported the potential role of APLN in KIRC tumor progression. Therefore, this paper hereby provides an analytical workflow to find hub regulators in cancer-stroma interactions.

Reactive oxygen species (ROS) oxidize surrounding molecules and thus impair their functions. Since mitochondria are a major source of ROS, suppression of ROS overproduction in the mitochondria is important for cells. Spontaneous transient depolarization of individual mitochondria is a physiological phenomenon widely observed from plants to mammals. Mitochondrial uncoupling can reduce ROS production; therefore, it is conceivable that transient depolarization could reduce ROS production. However, transient depolarization has been observed with increased ROS production. Therefore, the exact contribution of transient depolarization to ROS production has not been elucidated. In this study, we examined how the spontaneous transient depolarization occurring in individual mitochondria affected ROS production. When the matrix pH increased after the addition of malate or exposure of the isolated mitochondria to a high-pH buffer, transient depolarization was stimulated. Similar stimulation by an increased matrix pH was also observed in the mitochondria in intact H9c2 cells. Modifying the mitochondrial membrane potential and matrix pH by adding K+ in the presence of valinomycin, a K+ ionophore, clarified that an increase in the matrix pH is a major cause of ROS generation. When we added ADP in the presence of oligomycin to suppress the transient depolarization without decreasing the matrix pH, we observed the suppression of mitochondrial respiration, increased matrix pH, and enhanced ROS production. Based on these results, we propose a model where spontaneous transient depolarization occurs during increased proton influx through proton channels opened by increased matrix pH, leading to the suppression of ROS production. This study improves our understanding of mitochondrial behavior.

The risk of malignant transformation of intraductal papillary mucinous neoplasm (IPMN) is presently assessed using imaging, which remains unsatisfactory. Given the high viscosity of pancreatic juice, pancreatic juice cytology (PJC) is considered an investigational procedure. We previously demonstrated that the diagnostic performance of PJC was improved via synthetic secretin loading in pancreatic ductal carcinoma. This study aimed to evaluate the efficacy of synthetic secretin-loaded PJC (S-PJC) for IPMN. The usefulness and safety of S-PJC were prospectively evaluated in 133 patients with IPMN. Overall, 92, 12, and 26 patients had branch duct, main duct, and mixed-type lesions, respectively. The risk classifications based on the 2017 international consensus guidelines were high-risk stigmata, worrisome features, and no risk in 29, 59, and 45 patients, respectively. Synthetic secretin loading improved the sensitivity of PJC from 50.0% to 70.8%. Complications included 13 (9.8%) cases of mild pancreatitis, 1 (0.8%) case of acute cholangitis, and 1 (0.8%) case of Mallory–Weiss syndrome, all of which resolved with conservative treatment. In conclusion, synthetic secretin-loaded PJC improved the diagnostic performance of cytology for malignant IPMN. We recommend using synthetic secretin-loaded PJC for the preoperative pathological diagnosis of malignant IPMN in clinical settings.

INTRODUCTION:Non-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker. METHODS:Eighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control. One patient was excluded due to low RT-PCR signal. RESULTS:Compared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, low-density-lipoprotein cholesterol and non-high-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism-related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379. CONCLUSIONS:Serum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.

This randomized trial aimed to compare the safety and efficacy of the GAGLESS mouthpiece for esophagogastroduodenoscopy (EGD) with that of the conventional mouthpiece. In all, 90 participants were divided into the GAGLESS mouthpiece and conventional mouthpiece groups. The primary endpoint was the severity of pain using the visual analog scale (VAS), and secondary endpoints were examination time, past history of endoscopy, success of the procedure, systolic (SBP) and diastolic (DBP) blood pressure, oxygen saturation, pulse rate before and after EGD, and adverse events. Endoscopy was completed in all cases, and no complications were observed. VAS, when passing the scope through the pharynx, was 2.5 ± 2.4 and 2.0 ± 1.9 cm (p = 0.24) in the conventional and GAGLESS groups, respectively, and that, throughout the examination, was 2.5 ± 2.4 and 1.7 ± 1.5 cm (p = 0.06), respectively. The difference in blood pressure between the GAGLESS and conventional groups was not significant for SBP (p = 0.08) and significant for DBP (p = 0.03). The post-EGD difference in DBP was significantly lower in the GAGLESS group than in the conventional group. The results indicate that GAGLESS mouthpieces had a lower VAS during endoscopy than the conventional mouthpieces, and the changes in blood pressure were smaller with the GAGLESS mouthpiece.

BACKGROUND & AIMS:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease (NAFLD), and the pathogenic differences between SS and NASH remain unclear. MicroRNAs (miRNAs) are endogenous, non-coding, short RNAs that regulate gene expression. The aim of this study was to use animal models and human samples to examine the relationship between miRNA expression profiles and each type of NAFLD (SS and NASH). METHODS:DD Shionogi, Fatty Liver Shionogi (FLS) and FLS ob/ob mice were used as models for normal control, SS and NASH, respectively. Microarray analysis and real-time PCR were used to identify candidate NAFLD-related miRNAs. Human serum samples were used to examine the expression profiles of these candidate miRNAs in control subjects and patients with SS or NASH. RESULTS:Fourteen miRNAs showed clear expression differences among liver tissues from SS, NASH, and control mice with good reproducibility. Among these NAFLD candidate miRNAs, seven showed similar expression patterns and were upregulated in both SS and NASH tissues; these seven candidate miRNAs mapped to an miRNA cluster in the 14q32.2 maternally imprinted region delineated by delta-like homolog 1 and type III iodothyronine deiodinase (Dlk1-Dio3 mat). Software-based predictions indicated that the transforming growth factor-β pathway, insulin like growth factor-1 and 5' adenosine monophosphate activated protein kinase were potential targets of theses Dlk1-Dio3 mat NAFLD candidate miRNAs. In addition, serum samples from patients with SS or NASH differed markedly with regard to expression of the putative Dlk1-Dio3 mat miRNAs, and these differences accurately corresponded with NAFLD diagnosis. CONCLUSION:The expression profiles of seven miRNAs in 14q32.2 mat have high potential as biomarkers for NAFLD and for improving future research on the pathogenesis and treatment of NASH.

Background and study aims: Specimens collected by fine needle are microscopic and contain blood; therefore, the presence of a target specimen within a sample is often difficult to confirm. Although rapid on-site evaluation (ROSE) during endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) is beneficial, many health care facilities are unable to apply this technique due to a lack of cytopathologists. The aim of this study was to develop and validate a device that detects the target specimen within pancreatic tumor EUS-FNA samples. Patients and methods: Fifty-eight consecutive patients with solid pancreatic masses were studied for a preliminary case series at a tertiary-care university hospital (Tottori University Hospital, Yonago, Japan). The material collected was checked with a target sample check illuminator (TSCI) and was evaluated by one cytopathologist. Results: The agreement rate between the TSCI and histopathology was 93.7 %. Further testing procedures were not needed in 91.4 % of patients, and the mean number of needle punctures was 1.2 after a single pass using TSCI. No adverse events were encountered with the procedure. Conclusions: With the introduction of the TSCI in EUS-FNA, it became possible to both collect the minimum necessary target samples by EUS-FNA and to end further procedures, even without performing ROSE.