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.

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.

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.

Frequency-segmented power amplification using multi-band radio frequency amplifiers to produce a high-voltage pulse.

A method of frequency-segmented power amplification using multiband radio frequency (RF) amplifiers was proposed to generate stable and arbitrary high-voltage pulses. The concept behind this method is that an arbitrary pulse with a specified duration and sharp edges can be reconstructed using only several frequencies, and most of the power is concentrated on the fundamental frequency. The high-voltage pulse can, therefore, be obtained by amplifying each segmented frequency and then combining it with the RF power combiners. To correct the frequency-dependent group delays and gain of the amplifier circuit and to perform fine-tuning of the pulse structure, a seed pulse is divided into several lines that have bandpass filters, variable delay lines, variable power attenuators, and main RF amplifiers. A prototype pulse amplifier was designed and fabricated based on this method to generate rectangular pulses for the electron beam chopper of an x-ray free-electron laser injector. Flat and stable pulses with a 2 ns width of 0.2 kV height, peak-to-peak flat top of 0.8%, and route-mean-squared peak jitter of less than 0.2% were successively generated in both single- and multi-bunch structures. In the future, this type of pulse generator will play an important role in accelerators that require complicated and precise beam handling at high repetition rates of kHz or MHz.

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.

Forced harmonic oscillator interpreted as diffraction of light.

We investigate a simple forced harmonic oscillator with a natural frequency varying with time. It is shown that the time evolution of such a system can be written in a simplified form with Fresnel integrals, as long as the variation of the natural frequency is sufficiently slow compared to the time period of oscillation. Thanks to such a simple formulation, we found that a forced harmonic oscillator with a slowly varying natural frequency is essentially equivalent to diffraction of light.

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.

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.

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 stable pulsed power supply for multi-beamline XFEL operations.

Since an X-ray Free Electron Laser (XFEL) facility is a linac-based single-user machine, a multi-beamline mode of operation, which improves the efficiency of user experiments, is critical for accommodating users' rapidly increasing demand for beamtime. A key supporting technology is a highly stable pulsed power supply (PS), which enables stable XFEL operations by precisely switching the beam route. We developed a high-power pulsed PS to drive a kicker magnet installed in a SACLA's beam switching system. SiC MOSFETs were adapted as switching elements to reduce the required size and to increase the electric power efficiency. The PS we developed provides two key capabilities: (i) a high current stability of 20 ppm (peak-to-peak) at a peak power of 0.24 MW and (ii) generation of controllable, bipolar, and trapezoidal current waveforms at 60 Hz. This paper describes the overall concept, the detailed design, the performance achieved, and the initial beam test results.

Potent apoptosis-inducing activity of erypoegin K, an isoflavone isolated from Erythrina poeppigiana, against human leukemia HL-60 cells.

Erypoegin K is an isoflavone isolated from the stem bark of Erythrina poeppigiana. It contains a furan group at the A-ring of the core isoflavone structure and can inhibit the activity of glyoxalase I, an enzyme that catalyzes the detoxification of methylglyoxal (MG), a by-product of glycolysis. In the present study, we found that erypoegin K has a potent cytotoxic effect on human leukemia HL-60 cells. Its cytotoxic effect was much stronger than that of a known glyoxalase I inhibitor S-p-bromobenzylglutathione cyclopentyl diester. Conversely, erypoegin K demonstrated weak cytotoxicity toward normal human peripheral lymphocytes. The treatment of HL-60 cells with erypoegin K significantly induced caspase-3 activity, whereas the pretreatment of the cells with caspase-3 inhibitor suppressed erypoegin K-induced cell death. Furthermore, nuclear condensation and apoptotic genome DNA fragmentation were observed in erypoegin K-treated HL-60 cells. These results indicated that the observed cell death was mediated by apoptosis. In addition, the toxic compound MG was highly accumulated in the culture medium of erypoegin K-treated HL-60 cells, suggesting that cell apoptosis was triggered by extracellular MG. The present study showed that erypoegin K has a potent apoptosis-inducing effect on cancerous cell lines, such as HL-60.

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.

A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor-Reactive B Cells.

Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG. The effects of AChR-Fc in vivo were also examined using rat MG models. AChR-Fc bound to anti-AChR antibodies and exhibited cytotoxicity against patient-derived antibody-producing B cells. Additionally, a dose-dependent improvement in the clinical signs of disease was observed in a rat MG model. AChR-Fc can diminish signs of MG by neutralizing anti-AChR antibodies and enhancing cytotoxicity against autoantibody-producing B cells. Thus, AChR-Fc can be a novel therapeutic biomolecule for patients with MG.

Fanconi Syndrome Associated with Hyponatremia in Two Patients with Legionella Pneumonia.

Legionella pneumophila is a cause of community-acquired pneumonia that is reported to induce electrolyte disorders, including hyponatremia, hypokalemia, and hypophosphatemia. We herein report two Japanese men with Legionella pneumonia and hyponatremia and hypophosphatemia. These findings were associated with an elevation of urinary low-molecular-weight tubular protein, including urinary ß2-microglobulin, N-acetyl-ß-D-glucosaminidase, the fractional excretion of phosphate and uric acid, and the presence of glycosuria and panaminoaciduria, suggesting that their electrolyte disorders had been caused by Fanconi syndrome. In these two cases, hyponatremia was probably due to salt wasting. Electrolyte disorders caused by Legionella pneumonia are corrected by treatment of the primary disease and fluid administration.