Critical neuroprotective roles of heme oxygenase‐1 induction against axonal injury‐induced retinal ganglion cell death

Although axonal damage induces significant retinal ganglion cell (RGC) death, small numbers of RGCs are able to survive up to 7 days after optic nerve crush (NC) injury. To develop new treatments, we set out to identify patterns of change in the gene expression of axonal damage‐resistant RGCs. To compensate for the low density of RGCs in the retina, we performed retrograde labeling of these cells with 4Di‐10ASP in adult mice and 7 days after NC purified the RGCs with fluorescence‐activated cell sorting. Gene expression in the cells was determined with a microarray, and the expression of Ho‐1 was determined with quantitative PCR (qPCR). Changes in protein expression were assessed with immunohistochemistry and immunoblotting. Additionally, the density of Fluoro‐gold‐labeled RGCs was counted in retinas from mice pretreated with CoPP, a potent HO‐1 inducer. The microarray and qPCR analyses showed increased expression of Ho‐1 in the post‐NC RGCs. Immunohistochemistry also showed that HO‐1‐positive cells were present in the ganglion cell layer (GCL), and cell counting showed that the proportion of HO‐1‐positive cells in the GCL rose significantly after NC. Seven days after NC, the number of RGCs in the CoPP‐treated mice was significantly higher than in the control mice. Combined pretreatment with SnPP, an HO‐1 inhibitor, suppressed the neuroprotective effect of CoPP. These results reflect changes in HO‐1 activity to RGCs that are a key part of RGC survival. Upregulation of HO‐1 signaling may therefore be a novel therapeutic strategy for glaucoma. © 2014 Wiley Periodicals, Inc.     

Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature

Sinus bradycardia is a well-known consequence of stimulation of presynaptic α₂ adrenergic receptors due the adminstration of dexmedetomidine. One of the most serious adverse effects of dexmedetomidine is cardiac arrest. Some cases demonstrating such an arrest due to the indiscriminate use of this drug were recently reported. We continuously administered dexmedetomidine to a 56-year-old male patient at a rate of 0.3 μg/kg/h (lower than the recommended dose) without initial dosing for sedation in an intensive care unit. The patient had undergone open cardiac surgery and atrial pacing was maintained at a fixed rate, 90/min. The PQ interval in electrocardiography gradually prolonged during the infusion; finally, complete atrioventricular block and subsequent cardiac arrest occurred. Immediate cardiopulmonary resuscitation was carried out, including re-intubation, and recovery of spontaneous circulation was attained 15 min after the event. The patient was discharged from hospital on the 25th postoperative day without any neurological complications.     

The area and attachment abnormalities of the gubernaculum in patients with undescended testes in comparison with those with retractile testes

Purpose

In order to evaluate the gubernaculum (GN) abnormalities quantitatively in patients with undescended testes (UDT), the area and attachment site of the gubernaculum were evaluated.

Patients and methods

Sixty-seven testes from 61 patients with an undescended testis treated in the past 11 years at our institution were examined. Using intraoperative photographs or DVDs, the area of the GN inside the processus vaginalis was measured, and the ratio to that of the testis was determined. When the GN was attached to the vas deferens, the GN distance from the testis was also measured, and the ratio to that of the transverse length of the testis (deviation index) was calculated. Reference values were obtained from 23 testes from 15 patients with mobile testes.

Results

In cases with mobile testes, the GN attached to the bottom of the testis, and involved the lower pole of the epididymis. Even though the GN was attached to the bottom of the testis in 43 testes in the UDT patients (64 %), the GN was found to be elongated. The mean GN area ratio was 1.58 (1SD, 0.6) in the UDT cases, in comparison to 0.47 (0.2) in the cases with mobile testes. The GN was attached to the vas deferens in 24 testes (36 %). The deviation index was 1.34 (1.0), but the GN area ratio of these cases was 1.56 (0.7), which was similar to that of the GN attached to the bottom of the testis.

Conclusion

The present study revealed that an increase in the GN area ratio was the most common imaging abnormality in cases with UDT.     

Synthesis of Co2FeGe Heusler alloy nanoparticles and catalysis for selective hydrogenation of propyne

Although intermetallic compounds are attracting attention of catalysis researchers, ternary intermetallic catalysts have scarcely been investigated due the difficulty of synthesizing supported nanoparticles. In this study, we successfully synthesized SiO₂ supported Co₂FeGe Heuslar alloy nanoparticles. This catalyst exhibited high catalytic performance for selective hydrogenation of propyne by nano-sizing.

Supported nanoparticles of Co₂FeGe Heusler alloy were successfully synthesized. The reaction rate per weight was increased 2000 times by nano-sizing.

An alloy is a solid mixture of two or more metallic elements. It is typically categorized into a solid solution and an intermetallic compound. In the former, different metal atoms randomly occupy lattice points, and the available range of chemical compositions is wide. In the latter, different metal atoms occupy specific lattice points, forming an ordered structure, and chemical compositions available are restricted to integer ratios. Thus, intermetallic compounds have unique electronic structures and unique atomic ordered surfaces, which are completely different from those of pure metals and solid solutions, resulting in novel catalytic properties.^1–6Along with a recent increasing interest in intermetallic catalysts, many binary compounds have been investigated as catalysts thus far; however, ternary compounds have scarcely been reported as catalysts. The number of possible elemental sets forming intermetallic compounds is much larger in ternary systems than binary ones.⁷ In addition, novel properties originating from synergy among different elements are more likely in ternary than binary systems; for example, in the La(Co or Ru)Si catalyst for ammonia synthesis, the hydrogen storage ability, the electride property, and the electron transfer from La to the active element (Co or Ru) are believed to play key roles.^8,9 Therefore, the discovery of various new catalysts is expected in ternary systems.Heusler alloys are a group of ternary intermetallic compounds described by X₂YZ with L2₁ structure (body-centered cubic basis) typically consisting of 8–12, 3–8, and 13–15 group elements for X, Y, and Z, respectively. This intermetallic group is popular as magnetic, thermoelectric, shape memory and topological materials while we have opened its new function as catalysts.^10–14 For selective hydrogenation of alkynes, Co₂FeGe Heusler alloy showed intrinsically high alkene selectivity; that is, it selectively hydrogenated alkynes but hardly hydrogenated alkenes even for hydrogenation of alkene reactants without alkynes.¹¹ In addition, the systematic control of catalytic properties by elemental substitution (Co₂Mn_xFe_1−xGa_yGe_1−y) was demonstrated. However, these catalysts were unsupported micron-sized powders with low surface areas (<0.1 m² g⁻¹) synthesized by metallurgical process (arc melting, annealing, crushing), which were far from being of practical use. Thus, synthesis of Co₂FeGe nanoparticles on solid supports, the standard form of catalysts assuring high activity per material cost, is desired.To synthesize supported intermetallic nanoparticles, much effort is required to optimize the synthesis conditions, especially in ternary systems. For Heusler alloys, supported nanoparticles with sufficient quality (small average size with sharp distribution of sizes, small second phases, ordering into L2₁ structure) have been reported only for Co₂FeGa^15–18 and Cu₂NiSn,¹⁹ the former of which was not for catalysts but mainly for magnetic materials. Thus, synthesizing supported Co₂FeGe nanoparticles with excellent catalytic properties for selective hydrogenation of alkynes is challenging. Nevertheless, we have achieved the synthesis of a variety of supported intermetallic nanoparticles,^4,6 including those using three elements; for example, Pt₃Fe_1−xM_x (M = Co, Ni, Cu, Zn, Ga, In, Sn, Pb)²⁰ and PtGa with deposition of Pb, In, or Sn.²¹In what follows, we report the synthesis of SiO₂ supported Co₂FeGe nanoparticles and its catalytic properties for selective hydrogenation of propyne (C₃H₄). The Co-based catalysts were prepared by the pore-filling (co-)impregnation method using SiO₂ as the support. Co(NO₃)₃·6H₂O (Wako, 98%), Fe(NO₃)₃·9H₂O (Sigma-Aldrich, 98%), (NH₄)₂GeF₆ (Aldrich, 99.9%) were used as the metal precursors, and the Co loading was adjusted at 3 wt%. The metal precursors were precisely weighed and dissolved together in deionized water so that the Co : Fe : Ge atomic ratio was 1.8 : 1 : 1. A mixed aqueous solution of metal precursors was added dropwise to ground dried silica gel (CARiACT G-6, Fuji Silysia, S_BET = 673 m² g⁻¹) so that the solutions just filled the pores of the silica gel (volume of solution: 1.6 mL per gram of silica). The mixtures were sealed with a piece of plastic film and kept overnight at room temperature, followed by freeze-drying under vacuum at 0 °C and further drying overnight in an oven at 90 °C. The resulting powder was calcined in air at 500 °C for 1 h, then reduced under flowing H₂ (0.1 MPa, 50 mL min⁻¹) at 800 °C for 1 h. Fig. 1 shows the powder X-ray diffraction (XRD) (Rigaku Ultima IV) pattern for the synthesized Co₂FeGe/SiO₂. Although tiny peaks of another phase (possibly CoGe) were detected by peak fitting, as shown in Fig. 1c and d, all visible peaks in Fig. 1a and b are assigned to Co₂FeGe Heusler phase (L2₁ structure). The peaks were broad, indicating the formation of nano-sized grains. The volume-weighted average grain size (d_XRD) was roughly estimated to be 13 nm from the full width at half maximum (FWHM) of the 220 peak using the Scherrer equation:d_XRD = Kλ/W cos θ1where K, λ, and W are the Scherrer constant, a wavelength, and a peak width, respectively; and 8/3π and FWHM were respectively adopted as K and W based on the assumption of spherical crystallites with lognormal size distribution.²² 111 and 200 superlattice peaks were certainly observed, meaning the formation of the ordered structure. These peaks are essentially very weak, because their intensities (I) are proportional to the square of the difference in the atomic scattering factors (F) of constituents, which are basically proportional to atomic numbers (I₁₁₁ ∝ |F_Fe − F_Ge|², I₂₀₀ ∝ |F_Co − (F_Fe + F_Ge)/2|²). Considering the anomalous scattering factors,²³ the Debye–Waller factors,^24,25 the multiplicity factor, and the Lorentz-polarization factor, I₁₁₁/I₂₂₀ = 0.007 and I₂₀₀/I₂₂₀ = 0.004 are derived for the perfectly ordered case. The broadening also makes it difficult to detect the superlattice peaks. Thus, the detection of the superlattice peaks indicates that the L2₁-ordered structure correctly formed even in nanograins. The degree of long-range order for Heusler alloys is evaluated typically by Webster''s model using S and α^10,26,27 as23where I₂₀₀, I₁₁₁, and I_fund are integrated intensities of 200 and 111 superlattice peaks, and a fundamental peak, respectively, and “exp” and “cal” respectively, means an experimental value and a calculated one for the perfectly ordered case. S corresponds to the long-range order parameter for binary alloys,²⁸ here describing the order between Co and Fe or Ge atoms (0 ≤ S ≤ 1); α describes the disorder between Fe and Ge atoms (0 ≤ α ≤ 0.5); thus, S = 1 with α = 0 means the perfect order. Although accurate evaluation of I₂₀₀ and I₁₁₁ was difficult because of too small an intensity, S and α were roughly estimated to be 0.8 and 0.0, respectively, when using the fitted data in Fig. 1c. Thus, the degree of long-range order was likely high.Open in a separate windowFig. 1XRD patterns for Co₂FeGe/SiO₂ (a) around superlattice peaks, (b) around fundamental peaks, (c) around superlattice peaks with fitting, and (d) around 220 peak with fitting. All peaks were normalized by integrated intensity of 220 peak. Green vertical lines in (a and b) show peak positions observed for unsupported Co₂FeGe powders. Blue dashed lines and red solid lines in (c and d) show backgrounds and sum of fitting lines, respectively. Inset of (c) displays magnification around 200 peak with fitting lines for 200 peak (green) and for second phase peak (orange) possibly originating from intermetallic CoGe phase, which also has a peak (orange) nearby 220 peak (green) in (d). Fitting was done using pseudo-Voigt function for peaks and polynomial function for backgrounds. Fig. 2a shows the image obtained by high-resolution high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) (FEI Titan G2). Brighter particles with relatively uniform diameters below about 30 nm are observed on darker skeletal matter, which indicates that Co₂FeGe nanoparticles are relatively homogeneously distributed on SiO₂ supports. The diameters of the brighter particles were counted, as shown in Fig. 2b. The size distribution was relatively narrow. The volume-weighted average diameter (d_TEM) was estimated to be 23.0 ± 5.3 nm byd_TEM = Σn_id_i⁴/Σn_id_i³4where n_i is the number of particles with the diameter d_i in Fig. 2b.^20,21Fig. 2c–f show elemental maps obtained by energy-dispersive X-ray (EDX) analysis. Co, Fe, and Ge were detected in the same regions, in which the brighter particles were observed in Fig. 2a. The quantitative analysis for the particle represented in Fig. 2g revealed that the chemical composition among Co, Fe, and Ge followed the precursor ratio and was close to the stoichiometry, as shown in Fig. 2h. These XRD and HAADF-STEM results clearly indicate the success of synthesizing Co₂FeGe nanoparticles on SiO₂ supports of sufficient quality.Open in a separate windowFig. 2Analysis by HAADF-STEM with EDX for Co₂FeGe/SiO₂: (a) HAADF-STEM image, (b) histogram of diameter for bright particles in (a), elemental maps for (c) Co, (d) Fe, and (e) Ge, (f) superimposed elemental map, (g) magnified elemental map, and (h) chemical composition in area marked by yellow circle in (g). In (h) bars display observed values and points indicate nominal values estimated from precursor ratio.The Co₂FeGe/SiO₂ was tested for catalytic reaction of the C₃H₄ hydrogenation using a standard flow reactor (see ref. 11 for details). Thirty mg of the catalyst was heated under H₂ gas flow at 800 °C for 1 h to remove surface oxides; then, feeding of a gaseous mixture of [0.1% C₃H₄/40% H₂/He balance] began at ambient temperature and pressure at 30 mL min⁻¹ (20 °C, 0.1 MPa) (space velocity: about 40 000 h⁻¹). The products were analyzed by gas chromatography (Agilent 490 Micro GC with PoraPLOT Q column) after waiting 30 min at each temperature. The conversion of C₃H₄ and the selectivity of products were estimated by56where C_feed, C_unreact, C_C3H6, and C_C3H8 were the concentrations of the feed C₃H₄, the unreacted C₃H₄, the produced C₃H₆, and the produced C₃H₈, respectively. C_lost is the concentration of carbon species lost due to oligomerization or coking, which is estimated by C_lost = C_feed − C_unreact − C_C3H6 − C_C3H8. Fig. 3a shows the results of the catalytic test. The carbon lost was negligible. The C₃H₆ selectivity was as high as over 70% even when the C₃H₄ conversion was 100%. In general, strong adsorption of C₃H₄ prevents re-adsorption of C₃H₆, which suppresses the further hydrogenation of C₃H₆, resulting in high C₃H₆ selectivity when the C₃H₄ conversion is below 100%. Once all C₃H₄ is consumed, C₃H₆ is quickly hydrogenated; thus, the C₃H₆ selectivity drastically decreases once the C₃H₄ conversion achieves 100% in most catalysts, including pure metals^29,30 and Co₂FeGa¹¹ (Fig. S1a and b^†). Therefore, the Co₂FeGe/SiO₂ synthesized here has an intrinsic selectivity for C₃H₆ as well as the unsupported Co₂FeGe powders synthesized metallurgically, the C₃H₆ selectivity of which was over 90% even when the C₃H₄ conversion was 100% (Fig. S2^†).¹¹ The reaction rate per weight of Co used was significantly enhanced up to as much as 2000 times by nano-sizing compared with the unsupported one, as shown in Fig. 3b. In terms of stability, a small deactivation was observed in the cooling process after heating up to 200 °C (Fig. S3^†), likely due to oligomerization or coking, while the C₃H₆ selectivity was improved over 90%.Open in a separate windowFig. 3(a) Catalytic properties of Co₂FeGe/SiO₂ for C₃H₄ hydrogenation, (b) C₃H₄ reaction rate per weight of Co at 75 °C for Co₂FeGe/SiO₂ (“nano”) and unsupported Co₂FeGe (“unsupported”), (c) C₃H₆ conversion for Co₂FeGe/SiO₂ in C₃H₆ hydrogenation. Reaction conditions in (c) were the same as those in (a) except the reactant, which was [0.1% C₃H₆/40% H₂/He-balance] in (c).To reveal the reason for the lower C₃H₆ selectivity of the Co₂FeGe/SiO₂ than that of the unsupported Co₂FeGe, the catalytic test for C₃H₆ hydrogenation was conducted in the same manner as the C₃H₄ hydrogenation as shown in Fig. 3c. A certain amount of C₃H₆ was converted to C₃H_8, whereas it was scarcely converted by the unsupported one.¹¹ This means the presence of the sites that further hydrogenate C₃H₆ in the C₃H₄ hydrogenation. For ordinary catalysts, the conversion is larger for the C₃H₆ hydrogenation than C₃H₄ hydrogenation at a lower temperature region in these reaction conditions¹¹ (Fig. S1^†). The larger conversion of C₃H₆ than C₃H₄ at ≤75 °C for the Co₂FeGe/SiO₂ (Fig. 3a and c) thus also indicates the presence of non-selective sites for the C₃H₄ hydrogenation. An anomaly at 175 °C in Fig. 3c is likely a result of conflict between the acceleration of reaction and the deceleration of C₃H₆ adsorption along with increasing temperature, which is often observed.¹¹Taking into account the origin of the high alkene selectivity that inactive Ge atoms shrink the size of active ensembles and thereby prevent the re-adsorption of alkene molecules, which is indicated from electronic structures,¹¹ two candidates are considered for the non-selective sites. One is a monometallic Co ensemble. In this impregnation synthesis, a part of the particles likely have chemical compositions that deviate from the target value. In particles with excess Co, monometallic Co ensembles should form, which is active for hydrogenation but not selective, as indicated by the tests using Co/SiO₂ (Fig. S1a and c^†). Actually, Co₂FeGe/SiO₂ catalysts preliminary prepared with the atomic ratio of Co : Fe: Ge = 2 : 1 : 1 loaded exhibited a poor selectivity (Fig. S4a^†) in contrast to the present catalyst (loaded Co : Fe : Ge = 1.8 : 1 : 1), and the former showed an extra peak in the temperature programmed CO desorption profile as well as the pure Co in addition to the peaks for the unsupported Co₂FeGe (Fig. S4b^†).³¹ The other candidate for non-selective sites is a specific site formed by nano-sizing, such as the corner and the edge. These low-coordinated sites are generally active but in different environments from the terrace sites; thus, they can be non-selective. A tiny amount of the second phase CoGe is unlikely as the candidate because a high ethylene selectivity in selective hydrogenation of acetylene by CoGe has been reported.³²Although it cannot be concluded whether the Co ensembles or the specific sites dominated the reduction of selectivity, the selectivity will increase up to the value for the unsupported one if the non-selective sites are identified and removed. Actually, the C₃H₆ selectivity was improved along with the deactivation (Fig. S3^†), indicating that the non-selective sites were killed by carbon deposition due to oligomerization or coking. Nevertheless, over 70% for C₃H₆ selectivity at 100% conversion of C₃H₄ is high enough for the condition under abundant hydrogen (C₃H₄ : H₂ = 1 : 400). This high selectivity was also confirmed in the C₃H₄ hydrogenation in the presence of abundant C₃H₆ (Fig. S5^†). These results indicate that the excellent catalytic properties of intermetallic micro-powders can be conserved in their nanoparticles. The reaction rate of C₃H₄ per surface area of Co₂FeGe was roughly estimated to be 1.2 × 10⁻⁷ mol s⁻¹ m⁻² at 75 °C by assuming the 23 nm-spheres with density of 8.66 g cm⁻³ (estimated by XRD for the unsupported one and using atomic weights). The value for the unsupported one was 4.1 × 10⁻⁸ mol s⁻¹ m⁻² at 75 °C. Although the estimation was very approximate, it can at least be said that the reaction rate did not decrease, or rather, it seems that the reaction rate somewhat increased by nano-sizing. This fact also assures the conservation of intrinsic catalytic properties after nano-sizing, while which increases the surface energy, enhancing the adsorption of reactant species, thereby possibly increasing the reaction rate.The catalytic performance is compared with those of other supported intermetallic catalysts reported (

Neural properties of fundamental function encoding of sound selectivity in the female avian auditory cortex

Zebra finches (Taeniopygia guttata) use their voices for communication. Song structures in the songs of individual males are important for sound recognition in females. The caudomedial mesopallium (CMM) and nidopallium (NCM) are known to be essential higher auditory regions for sound recognition. These two regions have also been discussed with respect to their fundamental functions and song selectivity. To clarify their functions and selectivity, we investigated latencies and spiking patterns and also developed a novel correlation analysis to evaluate the relationship between neural activity and the characteristics of acoustic factors. We found that the latencies and spiking patterns in response to song stimuli differed between the CMM and NCM. In addition, our correlation analysis revealed that amplitude and frequency structures were important temporal acoustic factors for both regions. Although the CMM and NCM have different fundamental functions, they share similar encoding systems for acoustic factors.     

Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis.

BACKGROUND: Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. METHODS: Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. RESULTS: Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. CONCLUSIONS: It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.     

Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems. Given these commonalities, we hypothesized that a related protein, EWSR1 (Ewing sarcoma breakpoint region 1), might also exhibit similar properties and therefore could contribute to disease. Here, we report an analysis of EWSR1 in multiple functional assays, including mutational screening in ALS patients and controls. We identified three missense variants in EWSR1 in ALS patients, which were absent in a large number of healthy control individuals. We show that disease-specific variants affect EWSR1 localization in motor neurons. We also provide multiple independent lines of in vitro and in vivo evidence that EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila. Postmortem analysis of sporadic ALS cases also revealed cytoplasmic mislocalization of EWSR1. Together, our studies highlight a potential role for EWSR1 in ALS, provide a collection of functional assays to be used to assess roles of additional RNA-binding proteins in disease and support an emerging concept that a class of aggregation-prone RNA-binding proteins might contribute broadly to ALS and related neurodegenerative diseases.     

Risk factors and prediction of bleeding after gastric endoscopic submucosal dissection in patients on antithrombotic therapy: newly developed bleeding prediction application software,SAMURAI model

Bleeding after gastric endoscopic submucosal dissection (ESD) remains problematic, especially in patients receiving antithrombotic therapy. Therefore, this study aimed to identify the risk factors. In this retrospective study, patients (n = 1,207) who underwent gastric ESD while receiving antithrombotic therapy were enrolled at Osaka Medical and Pharmaceutical University Hospital and 18 other referral hospitals in Japan. Risks of post-ESD bleeding were calculated using multivariable logistic regression. The dataset was divided into a derivation cohort and a validation cohort. We created a prediction model using the derivation cohort. The accuracy of the model was evaluated using the validation cohort. Post-ESD bleeding occurred in 142 (11.8%) participants. Multivariable analysis yielded an odds ratio of 2.33 for aspirin, 4.90 for P2Y12 receptor antagonist, 1.79 for cilostazol, 0.95 for other antithrombotic agents, 6.53 for warfarin, 5.65 for dabigatran, 7.84 for apixaban, 10.45 for edoxaban, 6.02 for rivaroxaban, and 1.46 for heparin bridging. The created prediction model was called safe ESD management using the risk analysis of post-bleeding in patients with antithrombotic therapy (SAMURAI). This model had good predictability, with a C-statistic of 0.77. In conclusion, use of the SAMURAI model will allow proactive management of post-ESD bleeding risk in patients receiving antithrombotic therapy.