Endoscopic Diagnosis of Epithelial Subtypes of Superficial Non-Ampullary Duodenal Epithelial Tumors using Magnifying Narrow-Band Imaging.

INTRODUCTION: Superficial non-ampullary duodenal epithelial tumors (SNADETs) include low-grade adenoma (LGA) and high-grade adenoma or carcinoma (HGA/Ca) and are classified into two different epithelial subtypes, gastric-type (G-type) and intestinal-type (I-type). We attempted to distinguish them by endoscopic characteristics including magnifying endoscopy with narrow-band imaging (M-NBI). METHODS: Various endoscopic and M-NBI findings of 286 SNADETs were retrospectively reviewed and compared between G- and I-types and histological grades. M-NBI findings were divided into four patterns based on the following vascular patterns; absent, network, intrastructural vascular (ISV), and unclassified. Lesions displaying a single pattern were classified as mono-pattern and those displaying multiple patterns as mixed-pattern. Lesions showing CDX2 positivity were categorized as I-types and those showing MUC5AC or MUC6 positivity were categorized as G-types based on immunohistochemistry. RESULTS: Among 286 lesions, 23 (8%) were G-type and 243 (85%) were I-type. More G-type lesions were located oral to papilla (91.3 vs. 45.6%, p < 0.001), and had protruding morphology compared to those of I-types (65.2 vs. 14.4%, p < 0.001). The major M-NBI pattern was ISV in G-type (78.2 vs. 26.3%, p < 0.001), and absent for I-type (0 vs. 34.5%, p = 0.003). Three endoscopic characteristics; location oral to papilla, protruding morphology, and major M-NBI pattern (ISV) were independent predictors for G-type. Mixed-pattern was more common in HGA/Ca than LGA for I-type (77.0 vs. 58.8%, p = 0.01); however, there was no difference for those in G-type. CONCLUSION: Endoscopic findings including M-NBI are useful to differentiate epithelial subtypes.

Endoscopic pressure study integrated system using an ultrathin gastroscope for the functional assessment of the lower esophageal sphincter.

OBJECTIVES: The endoscopic pressure study integrated system (EPSIS) represents an innovative approach for evaluating lower esophageal sphincter function by monitoring intragastric pressure using diagnostic gastroscopes. This study aimed to assess the feasibility and validity of employing ultrathin gastroscopes for EPSIS. METHODS: A retrospective analysis was conducted on a database of consecutive patients who underwent EPSIS using both ultrathin and regular gastroscopes between September 2021 and October 2023. The study compared EPSIS parameters between the two gastroscope types to evaluate the correlation of key metrics. RESULTS: Thirty patients underwent EPSIS with both ultrathin and regular gastroscopes. Significant positive correlations were observed in the pressure waveform: maximum intragastric pressure (mmHg) (ρ = 0.82, P < 0.001) and intragastric pressure gradient (mmHg/s) (ρ = 0.80, P < 0.001) when comparing the two gastroscopes. Maximum intragastric pressure (15.5 [5.3-20.3] vs. 18.5 [3.4-21.6], P < 0.001) and pressure gradient (0.16 [0.013-0.41] vs. 0.24 [0.0039-1.13], P < 0.001), (median [range]) were significantly lower with ultrathin gastroscopes. CONCLUSIONS: This study establishes that EPSIS parameters obtained with an ultrathin gastroscope exhibit a significant correlation with those obtained using a regular gastroscope, with each EPSIS parameter consistently lower. These findings support the viability of EPSIS for ultrathin gastroscopy and highlight its potential as a diagnostic tool for assessing lower esophageal sphincter function.

Spectral-brightness optimization of an X-ray free-electron laser by machine-learning-based tuning.

A machine-learning-based beam optimizer has been implemented to maximize the spectral brightness of the X-ray free-electron laser (XFEL) pulses of SACLA. A new high-resolution single-shot inline spectrometer capable of resolving features of the order of a few electronvolts was employed to measure and evaluate XFEL pulse spectra. Compared with a simple pulse-energy-based optimization, the spectral width was narrowed by half and the spectral brightness was improved by a factor of 1.7. The optimizer significantly contributes to efficient machine tuning and improvement of XFEL performance at SACLA.

Multilateral surface analysis of the CeB6 electron-gun cathode used at SACLA XFEL.

The CeB6(001) single crystal used as a cathode in a low-emittance electron gun and operated at the free-electron laser facility SACLA was investigated using cathode lens electron microscopy combined with X-ray spectroscopy at SPring-8 synchrotron radiation facility. Multilateral analysis using thermionic emission electron microscopy, low-energy electron microscopy, ultraviolet and X-ray photoemission electron microscopy and hard X-ray photoemission spectroscopy revealed that the thermionic electrons are emitted strongly and evenly from the CeB6 surface after pre-activation treatment (annealing at 1500°C for >1 h) and that the thermionic emission intensity as well as elemental composition vary between the central area and the edge of the old CeB6 surface.

Adaptive feedforward control of closed orbit distortion caused by fast helicity-switching undulators.

A new correction algorithm for closed orbit distortion based on an adaptive feedforward control (AFC) has been developed. At SPring-8, two helicity-switching twin-helical undulators (THUs) had been implemented with conventional feedforward corrections. However, the validity of these corrections turned out to be expiring due to unforeseen variation in the error magnetic fields with time. The developed AFC system has been applied to the THUs dynamically updating the feedforward table without stopping the helicity switching amid user experiments. The error sources in the two THUs are successfully resolved and corrected even while the two THUs are switching simultaneously with the same repetition period. The actual operation of the new AFC system enables us to keep the orbit variations suppressed with an accuracy at the sub-micrometre level in a transparent way for light source users.

(S)-Erypoegin K, an isoflavone isolated from Erythrina poeppigiana, is a novel inhibitor of topoisomerase IIα: Induction of G2 phase arrest in human gastric cancer cells.

Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has a single chiral carbon in its structure and exists naturally as a racemic mixture. Our previous study showed (S)-erypoegin K selectively exhibits potent anti-proliferative and apoptosis-inducing activity against human leukemia HL-60 cells. To identify the target molecule of (S)-erypoegin K, we employed the human cancer cell panel analysis (termed JFCR39) coupled with a drug sensitivity database of pharmacologically well-characterized drugs for comparison using the COMPARE algorithm. (S)-erypoegin K exhibited a similar profile to that of etoposide, suggesting the molecular target for erypoegin K may be topoisomerase II (Topo II). Subsequent experiments using purified human Topo IIα established that the (S)-isomer selectively stabilizes the cleavage complex composed of double-stranded plasmid DNA and the enzyme. Moreover, (S)-erypoegin K inhibited decatenation of kinetoplast DNA. Molecular docking studies clearly indicated specific binding of the (S)-isomer to the active site of Topo IIα involving hydrogen bonds that help stabilize the cleavage complex. (S)-erypoegin K displayed potent cytotoxic activity against two human gastric cancer cells GCIY and MKN-1 with IC50 values of 0.270 and 0.327 µM, respectively, and induced enzyme activities of caspase 3 and 9. Cell cycle analysis showed marked cell cycle arrest at G2 phase in both cell lines. (S)-erypoegin K also displayed significant antitumor activity toward GCIY xenografted mice. The present study suggests (S)-erypoegin K acts as a Topo II inhibitor to block the G2/M transition of cancer cells.

Induction of enantio-selective apoptosis in human leukemia HL-60 cells by (S)-erypoegin K, an isoflavone isolated from Erythrina poeppigiana.

Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has potent apoptosis-inducing effect on human leukemia HL-60 cells. Erypoegin K has a chiral carbon at the C-2'' position of its furan ring and naturally occurs as a racemic mixture of (S)- and (R)-isomers. In the present study, we semi-synthesized (RS)-erypoegin K from genistein and separated the optical isomers by HPLC using a chiral column to characterize its apoptosis-inducing activity. Apoptotic cell death was assessed by analyzing caspase-3 and caspase-9 activation, nuclear fragmentation, and genomic DNA ladder formation. (S)-erypoegin K showed exclusive anti-proliferative and apoptosis-inducing activity, with an IC50 value of 90 nM, about 50% lower than that of its racemic mixture (175 nM). By contrast, no apoptosis-inducing activity was shown by the (R)-isomer. In addition, methylglyoxal accumulation in the culture medium was observed only in cells treated with (S)-erypoegin K. These results demonstrated that (S)-erypoegin K is a unique bioactive component that has potent apoptosis-inducing activity on HL-60 cells.

Intravaginal administration of progesterone using a new technique for sustained drug release in goats.

The objective of the present study was to develop and evaluate a sustained release vaginal progesterone (P4) capsule containing a mixture of mucoadhesive polymer and silicone fluid. Goats were administered a gelatin capsule containing 0.4 g of P4 mixed in silicone fluid and either a hydroxypropylmethylcellulose (HM) or polyaclil starch (PA) base. The mean plasma P4 concentrations at 2 and 12 h after administration were significantly higher in goats treated with PA capsules than in those with HM capsules. The plasma P4 concentrations in goats treated with HM capsules increased and remained above 1.0 ng/ml for 96 h after administration, whereas the plasma P4 concentrations in goats treated with PA capsules remained above 1.0 ng/ml for only 24 h after administration. In the next experiment, an HM capsule was attached to a silicone device and inserted in the vagina for 10 days. The plasma P4 concentration remained similar to that of the natural luteal phase for 9 days. These results suggest that a mixture of mucoadhesive polymer and silicone fluid has the potential to be applied clinically as a sustained release base for estrus synchronization or hormonal therapy.

Multiple-beamline operation of SACLA.

The SPring-8 Ångstrom Compact free-electron LAser (SACLA) began parallel operation of three beamlines (BL1-3) in autumn 2017 to increase the user beam time of the X-ray free-electron laser. The success of the multiple-beamline operation is based on two technological achievements: (i) the fast switching operation of the SACLA main linear accelerator, which provides BL2 and BL3 with pulse-by-pulse electron beams, and (ii) the relocation and upgrade of the SPring-8 Compact SASE Source for BL1, for the generation of a soft X-ray free-electron laser. Moreover, the photon beamlines and experimental stations were upgraded to facilitate concurrent user experiments at the three beamlines and accommodate more advanced experiments.

Safety of Fibrinogen Concentrate and Cryoprecipitate in Cardiovascular Surgery: Multicenter Database Study.

OBJECTIVES: To investigate whether administering fibrinogen concentrate or cryoprecipitate is associated with increased postoperative thromboembolic events and improved mortality in patients undergoing thoracic aortic surgery. DESIGN: Multicenter retrospective cohort study using propensity-score analyses and multivariate logistic regression analysis to control for confounders. SETTING: Four hospitals (1 national cardiovascular center and 3 university hospitals). PARTICIPANTS: Patients undergoing thoracic aortic surgery with cardiopulmonary bypass between January 2010 and October 2012 (n = 1,047). INTERVENTIONS: Outcomes in patients treated with fibrinogen concentrate or cryoprecipitate (fibrinogen group) were compared with those who did not receive these products (no fibrinogen group) based on propensity-score matching. Multivariate logistic regression analysis then was performed to confirm the results. MEASUREMENTS AND MAIN RESULTS: Among 1,047 patients enrolled in this study, 247 patients received fibrinogen concentrate or cryoprecipitate. The median amount of administered fibrinogen was 3 g (interquartile range 2-4 g). Eighty-seven patients were excluded from the propensity-score matching because of missing data. Propensity-score-matched analysis showed no significant difference in the incidence of thromboembolic events or 30-day mortality rate between the groups. Multivariate analysis revealed that the fibrinogen group showed no significant difference in thromboembolic events (odds ratio 1.22; 95% confidence interval 0.76-1.95; p = 0.408) or mortality rate (odds ratio 0.44; 95% confidence interval 0.18-1.12; p = 0.081) compared with those in the no fibrinogen group. CONCLUSIONS: Administering fibrinogen concentrate or cryoprecipitate was associated with neither thromboembolic events nor 30-day mortality in patients undergoing thoracic aortic surgery. Administering fibrinogen concentrate or cryoprecipitate is safe and does not appear to increase thromboembolic events and mortality in thoracic aortic surgery patients.

A soft X-ray free-electron laser beamline at SACLA: the light source, photon beamline and experimental station.

The design and performance of a soft X-ray free-electron laser (FEL) beamline of the SPring-8 Compact free-electron LAser (SACLA) are described. The SPring-8 Compact SASE Source test accelerator, a prototype machine of SACLA, was relocated to the SACLA undulator hall for dedicated use for the soft X-ray FEL beamline. Since the accelerator is operated independently of the SACLA main linac that drives the two hard X-ray beamlines, it is possible to produce both soft and hard X-ray FEL simultaneously. The FEL pulse energy reached 110 µJ at a wavelength of 12.4 nm (i.e. photon energy of 100 eV) with an electron beam energy of 780 MeV.

Seasonal variations in bacterioplankton community structures in two small rivers in the Himi region of central Japan and their relationships with environmental factors.

The aim of this study was to improve our understanding of seasonal variations and the effects of physicochemical conditions on the bacterioplankton communities in two small rivers, the Moo and Nakayachi Rivers in the Himi region of central Japan. These rivers are inhabited by unionid freshwater mussels, which are used for oviposition by the endangered Itasenpara bitterling (Acheilognathus longipinnis). Water samples were collected every month between March 2011 and February 2012. Changes in bacterioplankton community structures were analysed using an approach that did not require cultivating the bacteria and involved PCR and denaturing gradient gel electrophoresis. The bacterioplankton community structures in the two rivers were similar in all seasons except winter. The bacterial sequences identified were dominated by typical freshwater Actinobacteria, Bacteroidetes, Cyanobacteria, α-Proteobacteria, and ß-Proteobacteria bacterioplankton. Many ß-Proteobacteria species were detected in all seasons, but Bacteroidetes species were dominant in the winter. The bacterioplankton community structures were affected by biochemical oxygen demand, chemical oxygen demand, chlorophyll-a concentration, water depth, and water temperature. These results provide a foundation for a more detailed understanding of the conditions that provide a suitable unionid habitat.

Temperature dependence on the pesticide sampling rate of polar organic chemical integrative samplers (POCIS).

Laboratory experiments were performed to determine the sampling rates of pesticides for the polar organic chemical integrative samplers (POCIS) used in Japan. The concentrations of pesticides in aquatic environments were estimated from the accumulated amounts of pesticide on POCIS, and the effect of water temperature on the pesticide sampling rates was evaluated. The sampling rates of 48 pesticides at 18, 24, and 30 °C were obtained, and this study confirmed that increasing trend of sampling rates was resulted with increasing water temperature for many pesticides.

Overview of the SACLA facility.

In March 2012, SACLA started user operations of the first compact X-ray free-electron laser (XFEL) facility. SACLA has been routinely providing users with stable XFEL light over a wide photon energy range from 4 to 15 keV and an ultrafast pulse duration below 10 fs. The facility supports experimental activities in broad fields by offering high-quality X-ray optics and diagnostics, as well as reliable multiport charge-coupled-device detectors, with flexible experimental configurations. A two-stage X-ray focusing system was developed that enables the highest intensity of 10(20) W cm(-2). Key scientific results published in 2013 and 2014 in diverse fields are reviewed. The main experimental systems developed for these applications are summarized. A perspective on the facility upgrade is presented.

Paraoxonase-1 suppresses experimental colitis via the inhibition of IFN-γ production from CD4 T cells.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, where excessive Th1 cell responses are observed. We performed experiments to identify immunologically bioactive proteins in human plasma and found that paraoxonase (PON)-1, which has esterase activity and is associated with high-density lipoproteins, inhibited the IFN-γ production by both murine and human differentiating Th1 cells. Trinitrobenzene sulfonic acid-induced colitis was attenuated by the administration of PON-1. The beneficial effects of PON-1 were associated with a reduced ratio of IFN-γ-producing CD4 T cells in the mesenteric lymph nodes and decreased production of T cell-related cytokines in the colon. PON-1 inhibited the TCR-induced activation of ERK-MAPK signaling and the nuclear translocation of NF-κB in CD4 T cells. Interestingly, an excessive CD4 T cell response was observed in PON-1-deficient mice under physiological and pathological conditions. Additionally, the efficacy of PON-1 or G3C9-C284A (G3C9), which shows a higher esterase activity than PON-1, on colitis was similar to that of an anti-TNF-α mAb, which is a clinically used CD treatment. Moreover, G3C9 more effectively suppressed CD4(+)CD45RB(high) cell transfer-induced chronic colitis in mice than did PON-1, and the efficacy of G3C9 against the colitis was similar to that of the anti-TNF-α mAb. Therefore, PON-1 (or G3C9) administration may be clinically beneficial for CD patients.

Optics for coherent X-ray applications.

Developments of X-ray optics for full utilization of diffraction-limited storage rings (DLSRs) are presented. The expected performance of DLSRs is introduced using the design parameters of SPring-8 II. To develop optical elements applicable to manipulation of coherent X-rays, advanced technologies on precise processing and metrology were invented. With propagation-based coherent X-rays at the 1 km beamline of SPring-8, a beryllium window fabricated with the physical-vapour-deposition method was found to have ideal speckle-free properties. The elastic emission machining method was utilized for developing reflective mirrors without distortion of the wavefronts. The method was further applied to production of diffraction-limited focusing mirrors generating the smallest spot size in the sub-10 nm regime. To enable production of ultra-intense nanobeams at DLSRs, a low-vibration cooling system for a high-heat-load monochromator and advanced diagnostic systems to characterize X-ray beam properties precisely were developed. Finally, new experimental schemes for combinative nano-analysis and spectroscopy realised with novel X-ray optics are discussed.

Control of damping partition numbers in a ring accelerator with rf electromagnetic fields.

A novel scheme to reduce transverse beam emittance in a ring accelerator is proposed by using a pair of coupling cavities as a basic unit to control damping partition numbers. As indicated by Robinson in 1958, a simple rf electromagnetic field (e.g., a TM210 mode by a single coupling cavity) cannot control the damping partition of three eigenoscillation modes in a ring accelerator due to the cancellation between the contributions from the magnetic and electric fields. Based on both analytical and numerical studies, we show that a pair of coupling cavities that satisfy phase and optics matching conditions can overcome this cancellation. The results indicate that the horizontal emittance is reducible to the theoretical limit based on the steady state condition and also, the emittance is reducible below the reduction limit under a nonsteady state by driving the coupling cavities with gated signals.

Apolipoprotein A-II suppressed concanavalin A-induced hepatitis via the inhibition of CD4 T cell function.

Con A-induced hepatitis has been used as a model of human autoimmune or viral hepatitis. During the process of identifying immunologically bioactive proteins in human plasma, we found that apolipoprotein A-II (ApoA-II), the second major apolipoprotein of high-density lipoprotein, inhibited the production of IFN-γ by Con A-stimulated mouse and human CD4 T cells. Con A-induced hepatitis was attenuated by the administration of ApoA-II. The beneficial effect of ApoA-II was associated with reduced leukocyte infiltration and decreased production of T cell-related cytokines and chemokines in the liver. ApoA-II inhibited the Con A-induced activation of ERK-MAPK and nuclear translocation of NFAT in CD4 T cells. Interestingly, exacerbated hepatitis was observed in ApoA-II-deficient mice, indicating that ApoA-II plays a suppressive role in Con A-induced hepatitis under physiological conditions. Moreover, the administration of ApoA-II after the onset of Con A-induced hepatitis was sufficient to suppress disease. Thus, the therapeutic effect of ApoA-II could be useful for patients with CD4 T cell-related autoimmune and viral hepatitis.

Inaccessible time to visual awareness during attentional blinks in macaques and humans.

Even when we attend to successive visual events, we often cannot notice an event occurring during a certain temporal window. Such an inaccessible time for visual awareness is known as "attentional blink" (AB). Whether AB is a phenomenon unique to humans or exists also in other animals is unclear. Using a dual-task paradigm shared between macaques and humans, we here demonstrate a nonhuman primate model of AB. Although macaques also showed behavioral signatures of AB, their AB effect lasted longer than that of humans. To map the relation between macaque and human ABs, we introduced a time warping analysis. The analysis revealed a formal structure behind the interspecies difference of AB; the temporal window of macaque AB was scaled from that of human AB. The present study opens the door to combining the approaches of neuroscience, psychophysics, and theoretical models to further identify a scale-invariant biological substrate of visual awareness.

Successful prevention of stenosis after circumferential endoscopic resection of esophageal cancer.

Circumferential resection of a >5-cm longitudinal mucosal defect following esophageal endoscopic submucosal dissection (ESD) is a risk factor for refractory stenosis. Circumferential ESD was performed in 3 patients with 64, 69, and 70 mm longitudinal mucosal defects. A local steroid injection was used to treat the postoperative ulcer, followed by an oral steroid. In all three cases, the ulcer healed without the need for endoscopic dilation. A combination of local injection and oral steroids effectively prevented esophageal stenosis in patients with high-risk stenosis after ESD.