A machine learning potential construction based on radial distribution function sampling.

Sampling reference data is crucial in machine learning potential (MLP) construction. Inadequate coverage of local configurations in reference data may lead to unphysical behaviors in MLP-based molecular dynamics (MLP-MD) simulations. To address this problem, this study proposes a new on-the-fly reference data sampling method called radial distribution function (RDF)-based data sampling for MLP construction. This method detects and extracts anomalous structures from the trajectories of MLP-MD simulations by focusing on the shapes of RDFs. The detected structures are added to the reference data to improve the accuracy of the MLP. This method allows us to realize a reasonable MLP construction for liquid water with minimal additional data. We prepare data from an H2O molecular cluster system and verify whether the constructed MLPs are practical for bulk water systems. MLP-MD simulations without RDF-based data sampling show unphysical behaviors, such as atomic collisions. In contrast, after applying this method, we obtain MLP-MD trajectories with features, such as RDF shapes and angle distributions, that are comparable to those of ab initio MD simulations. Our simulation results demonstrate that the RDF-based data sampling approach is useful for constructing MLPs that are robust to extrapolations from molecular cluster systems to bulk systems without any specialized know-how.

Cold snare defect protrusion and incomplete polyp resection after forced cold snare polypectomy: a prospective observational study.

BACKGROUND: Cold snare defect protrusions (CSDPs) that occur after cold snare polypectomy (CSP) are considered indicators of incomplete polyp resection (IPR). We have sometimes experienced difficulty resecting polyps with snaring alone; in such cases, a forcible pull on the snare by the endoscopist is necessary. We call this procedure "forced CSP (FCSP)." However, no previous studies have evaluated this procedure. METHODS: This was a prospective observational study. From November 2020 to June 2021, the frequency, safety, and validity of FCSP were evaluated at our hospital. We distinguished CSP with snaring alone performed by the assistant as conventional CSP, and CSP requiring a forcible pull on the snare by the endoscopist as FCSP. RESULTS: Of 1315 polyps removed, 105 underwent FCSP (8%). The perforation rate was 0% in both groups. The rate of CSDP after the procedure was 96.2% (101/105) with FCSP and 6.4% (77/1210) with conventional CSP (P<0.001). The rate of IPR was 12.5% (13/104) with FCSP and 6.2% (75/1208) with conventional CSP (P=0.02). Multivariable analysis identified polyps located in the cecum (risk ratio [RR], 1.13; 95%CI 1.050-1.179; P=0.003) and polyps ≥6mm in diameter (RR, 2.37; 95%CI 2.146-2.542; P<0.001) as independent risk factors for FCSP. CONCLUSIONS: FCSP was performed on 105 polyps (8%) in this study. FCSP may be associated with the occurrence of CSDP and IPR. Further studies are necessary to confirm our results.

Sequential Nucleophilic Substitution of Phosphorus Trichloride with Alcohols in a Continuous-Flow Reactor and Consideration of a Mechanism for Reduced Over-reaction through the Addition of Imidazole.

We demonstrate a sequential nucleophilic substitution of highly electrophilic and inexpensive phosphorus trichloride with three different alcohols in a continuous-flow reactor. A variety of alcohols including ones that contained acid- and/or basic-labile functionalities were rapidly reacted. A over nucleophilic substitution that occurred during reaction of the second alcohol was suppressed by the addition of imidazole. Density functional theory calculations of the sequential nucleophilic substitutions of alcohols were performed both with and without imidazole, and Berry pseudorotation was suggested as a rate-limiting step in both cases. Herein, we discuss the reasons for the decreased selectivity in the absence of imidazole as well as those for improved selectivity in the presence of imidazole during the second nucleophilic substitution.

Evaluation of cold snare polypectomy for small pedunculated (Ip) polyps with thin stalks: a prospective clinical feasibility study.

BACKGROUND: Although the use of cold snare polypectomy (CSP) has spread rapidly, no prospective studies evaluating the safety of CSP for pedunculated (Ip) polyps have been carried out. AIM: We performed this study to provide an accurate evaluation of the safety of CSP for Ip polyps. METHODS: This is a prospective study (UMIN000035687). From January 2019 to February 2021, the safety of CSP for use on Ip polyps <10 mm with thin stalks was evaluated at our hospital. The primary outcome measure was the incidence of bleeding (delayed post-polypectomy bleeding (DPPB) and immediate bleeding). RESULTS: During the study period, 89 consecutive patients (including 92 colonoscopies and 114 polyps) were prospectively enrolled. The en-bloc resection rate was 100%. The rate of DPPB after CSP was 0%, however, DPPB after conversion to HSP occurred in 1 case (33.3% (1/3)). The rate of immediate bleeding during CSP was 28.9% (33/114). Polyps with diameters ≥6 mm (OR (95% CI): 2.77 (1.041-7.376); p = .041) were extracted as independent risk factors for immediate bleeding during CSP for Ip polyps. In all, 104 (91.2%) polyps were low-grade adenomas, and the percentage of cases with negative pathological margins was 96.5% (110/114). CONCLUSIONS: CSP for Ip polyps was safe and had good outcomes. We believe that Ip polyps could be included as an indication for CSP, and that CSP may become the next step in the 'cold revolution.' To confirm our results and verify CSP's inclusion in future guidelines, prospective, randomized studies are necessary.

Management of Less Than 10-mm-Sized Pedunculated (Ip) Polyps with Thin Stalk: Hot Snare Polypectomy Versus Cold Snare Polypectomy.

BACKGROUND: Although the use of cold snare polypectomy (CSP) has spread rapidly, its safety for pedunculated (Ip) polyps remains controversial. In particular, the outcomes of hot snare polypectomy (HSP) and CSP for Ip polyps have not been previously compared. AIMS: This study evaluated whether the rate of delayed postpolypectomy bleeding (DPPB) after CSP for Ip polyps was higher than that after HSP for Ip polyps and compared other outcomes (the rates of immediate bleeding and pathological margins) between the HSP and CSP procedures. METHODS: A total of 5905 colorectal polyps in 4920 patients were resected at Omori Red Cross Hospital between October 2012 and June 2019. The polyps were divided into two groups: the HSP group (86 polyps, 64 patients) and the CSP group (102 polyps, 87 patients). The primary outcome measure was the incidence of DPPB. The secondary outcome measures were the incidences of immediate bleeding during the procedure and pathological margins of the resected specimen. RESULTS: The rate of immediate bleeding during CSP was significantly higher than that for the HSP group [38.2% (39/102) versus 3.5% (3/86); p < 0.001]. However, the rate of DPPB was significantly higher in the HSP group than in the CSP group [4.7% (4/86) versus 0% (0/102); p < 0.001]. The rate of DPPB after CSP was 0%. CONCLUSIONS: This is the first study to compare the outcomes of HSP and CSP for Ip polyps. CSP is safer than HSP for Ip polyps measuring < 10 mm in diameter.

Safety and efficacy of cold snare polypectomy for pedunculated (Ip) polyps measuring less than 10 mm in diameter.

BACKGROUND: Although cold snare polypectomy (CSP) has spread rapidly, it still remains controversial whether CSP is safe for pedunculated (Ip) polyps. PURPOSE: The aim of this study was to evaluate whether CSP for Ip polyps measuring less than 10 mm in diameter might be associated with an increased rate of delayed post-polypectomy bleeding (DPPB). METHODS: A total of 1641 colorectal polyps in 634 patients were resected at Omori Red Cross Hospital between April 2018 and December 2018. The polyps were divided into two groups depending on the morphology: the Ip group (90 polyps), and the non-Ip group (1551 polyps). RESULTS: Among the 1641 polyps, there was no case of DPPB, including in the Ip group. Immediate bleeding occurred in a total of 101 (6.2%) cases. Polyp location in the rectum (OR (95% CI), 3.61 (1.843-7.092); p < 0.001), polyp diameter ≥ 6 mm (OR (95% CI), 2.65 (1.702-4.132); p < 0.001), Ip morphology (OR (95% CI), 15.66 (9.262-26.49); p < 0.001), and treatment with antithrombotic agents (OR (95% CI), 2.18 (1.358-3.501); p = 0.0012) were identified as significant risk factors for immediate bleeding. CONCLUSIONS: This is the first study conducted to examine the safety of CSP for Ip polyps measuring less than 10 mm in diameter. CSP can be performed with a high level of safety even for Ip polyps. Based on our findings, we believe that Ip polyps could be included as an indication for CSP. However, prospective, randomized studies are necessary to confirm our results.

Gaussian process model of 51-dimensional potential energy surface for protonated imidazole dimer.

The goal of the present work is to obtain accurate potential energy surfaces (PESs) for high-dimensional molecular systems with a small number of ab initio calculations in a system-agnostic way. We use probabilistic modeling based on Gaussian processes (GPs). We illustrate that it is possible to build an accurate GP model of a 51-dimensional PES based on 5000 randomly distributed ab initio calculations with a global accuracy of <0.2 kcal/mol. Our approach uses GP models with composite kernels designed to enhance the Bayesian information content and represents the global PES as a sum of a full-dimensional GP and several GP models for molecular fragments of lower dimensionality. We demonstrate the potency of these algorithms by constructing the global PES for the protonated imidazole dimer, a molecular system with 19 atoms. We illustrate that GP models thus constructed can extrapolate the PES from low energies (<10 000 cm-1), yielding a PES at high energies (>20 000 cm-1). This opens the prospect for new applications of GPs, such as mapping out phase transitions by extrapolation or accelerating Bayesian optimization, for high-dimensional physics and chemistry problems with a restricted number of inputs, i.e., for high-dimensional problems where obtaining training data is very difficult.

Revisiting Formic Acid Decomposition by a Graph-Theoretical Approach.

Formic acid (HCOOH) is a suitable hydrogen storage material because of its high gravimetric and volumetric H2 capacities. Although H2 is produced by the thermal decomposition of HCOOH (HCOOH → H2 + CO2, dehydrogenation), the production of water and carbon monoxide (HCOOH → H2O + CO, dehydration) is the major pathway in HCOOH decomposition despite the thermodynamic favorability of the dehydrogenation process over the dehydration process. A large number of experimental and theoretical studies have suggested that both processes are competitive or that the dehydrogenation process has a lower activation energy in HCOOH decomposition. In the present work, we revisit the factors hindering the progress of the dehydrogenation process, using a whole chemical reaction network based on the graph theory. The calculated chemical reaction network shows that the factor controlling the dehydrogenation and dehydration processes is simple and fundamental and can be explained by the oxidation number of carbon and the betweenness centrality. Based on this understanding of the factors hindering the progress of dehydrogenation, the advantage of the dehydration process in HCOOH decomposition is discussed.

Safety of Cold Snare Polypectomy in Patients Receiving Treatment with Antithrombotic Agents.

BACKGROUND: With the aging of the population and rising incidence of thromboembolic events, the clinical use of antithrombotic agents is also increasing. There are few reports yet on the management of antithrombotic agent use in patients undergoing cold snare polypectomy (CSP). AIMS: The aim of this study was to evaluate whether continued administration of antithrombotic agents in patients undergoing CSP would be associated with an increased rate of delayed post-polypectomy bleeding (DPPB). METHODS: A total of 1177 colorectal polyps in 501 patients were resected at Omori Red Cross Hospital between October 2017 and March 2018. The polyps were divided into two groups depending on whether the patients received antithrombotic agent treatment or not: the antithrombotic group (911 polyps) and the no-antithrombotic group (266 polyps). RESULTS: Among the 1177 polyp resections, there was no case of DPPB, including in the antithrombotic group. Immediate bleeding occurred in a total of 63 (5.4%) cases. Polyp location in the rectum (OR (95% CI) 2.64 (1.223-5.679); p = 0.013), polyp size ≥ 6 mm (OR (95% CI) 4.64 (2.719-7.933); p < 0.001), polypoid growth pattern (OR (95% CI) 2.78 (1.607-4.793); p < 0.001), and antithrombotic agent use (OR (95% CI) 2.98 (1.715-5.183); p < 0.001) were identified as significant risk factors of immediate bleeding. CONCLUSIONS: Continued use of antithrombotic agents does not increase the risk of DPPB, even in those receiving multiple antithrombotic agents. Thus, it is safe to perform CSP even in multiple agent users. Prospective, randomized studies are necessary to confirm our results.

Comparison of computed tomography findings with clinical risks factors for endoscopic therapy in upper gastrointestinal bleeding cases.

Several risk scoring systems exist for acute upper gastrointestinal bleeding (UGIB). The clinical Rockall score (clinical RS) and the Glasgow-Blatchford score (GBS) are major risk scores that consider only clinical data. Computed tomography (CT) findings are equivocal in non-variceal UGIB. We compared CT findings with clinical data to predict mortality, rebleeding and need for endoscopic therapy in non-variceal UGIB patients. This retrospective, single-center study included 386 patients admitted to our emergency department with diagnosis of non-variceal UGIB by urgent endoscopy between January 2009 and March 2015. Multivariable logistic regression analysis was used to investigate CT findings and risk factors derived from clinical data. CT findings could not significantly predict mortality and rebleeding in non-variceal UGIB patients. However, upper gastrointestinal hemorrhage in CT findings better predicted the need for endoscopic therapy than clinical data. The adjusted odds ratios were 10.10 (95% CI 5.01-20.40) for clinical RS and 10.70 (95% CI 5.08-22.70) for the GBS. UGI hemorrhage in CT findings could predict the need for endoscopic therapy in non-variceal UGIB patients in our emergency department. CT findings as well as risk score systems may be useful for predicting the need for endoscopic therapy.

Local structure and hydrogen bond characteristics of imidazole molecules for proton conduction in acid and base proton-conducting composite materials.

Composite materials of acidic polymers and basic molecules have high proton-conductivity. Understanding the proton conduction mechanism of the composite materials, which depends on hydrogen bond characteristics, is an important task for developing materials with high proton-conductivity. This work is focused on poly(vinylphosphonic acid)-imidazole and alginic acid-imidazole as examples of composite materials of acidic polymers and basic molecules and examines the local structure and hydrogen bond characteristics of imidazole (Im) molecules in composite materials using density functional theory. The results show that Im molecules interact strongly with polymeric acids in these composite materials and that the interaction energy increases with the increase in the number of Im molecules. The rotational motion of Im molecules occurs in the segment where only Im molecules without excess protons are hydrogen-bonded to each other. The calculation results for the various segments, which depend on the hydrogen bonding environment, show that the proton conduction process in composite materials consists of the following steps: proton transfer in the segment where Im molecules interact with polymeric acids, proton transfer in the segment where Im molecules are affected by excess protons, and Grotthuss diffusion with reorientation of Im molecules in the segment where only Im molecules without excess protons are bonded to each other.

Potential energy construction in the diabatic picture for quantum mechanical rate constants of intermolecular proton transfer.

We propose a simple method for potential construction in the diabatic picture and the estimation of thermal rate constants for intermolecular proton transfer reactions using quantum dynamics simulations carried out on the constructed potentials. For symmetrical and asymmetrical proton transfer pairs, the obtained potentials and rate constants were in good agreement with the reference values. Furthermore, our method is used for the analysis of proton transfer in crystalline imidazolium succinate and discusses the proton conductivity in terms of intermolecular proton transfer. This approach can be used to estimate proton transfer rate constants for large molecular systems, even when the calculation of the transition state is impossible.

The α-glucosidase inhibitor voglibose stimulates delayed gastric emptying in healthy subjects: a crossover study with a 13C breath test.

The gastrointestinal effects of α-glucosidase inhibitors have not been sufficiently investigated. The aim of this study was to determine whether a single dose of pre-prandial voglibose might affect the rate of gastric emptying, determined using the 13C breath test. Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted overnight and received 0.2 mg voglibose or a placebo 2 h before a test meal. They were then served a liquid test meal consisting of 200 kcal per 200 ml that contained 100 mg 13C-acetate. Breath samples were collected under both conditions until 150 min after the meal. A comparison of the control and voglibose conditions revealed that for gastric emptying rates (with values expressed as median: range), T1/2 [(87.9: 78.0-104.9 min) vs (88.4: 74.3-106.3 min), p = 1], Tlag [(47.1: 39.6-60.1 min) vs (45.4: 31.2-63.3 min), p = 0.432], ß [(1.89: 1.68-2.18) vs (1.90: 1.35-2.15), p = 0.846] and κ [(0.81: 0.71-0.98) vs (0.81: 0.50-0.94), p = 0.922] did not significantly differ between conditions. A significant difference between the control and voglibose conditions was found for the GEC [(4.28: 4.09-4.44) vs (4.06: 3.69-4.50), p = 0.0138]. In conclusion, this study demonstrated that the ingestion of oral voglibose led to delayed gastric emptying of a liquid meal.

An NMR study on the mechanisms of freezing and melting of water confined in spherically mesoporous silicas SBA-16.

Thermodynamic and dynamic properties of water confined in mesoporous silica glass SBA-16 were investigated by DSC, and (1,2)H NMR spectroscopy and (2)H NMR spin-lattice relaxation time (T1) as a function of pore size. SBA-16 possesses the main spherical pores, interconnecting channels and micropores (corona). Water in the characteristic spherical pores of SBA-16 freezes at the homogeneous nucleation temperature of water. Between room and freezing temperatures, the correlation time of the isotropic rotation of water in the pores of SBA-16 followed the Vogel-Fulcher-Tammann (VFT) relation, which reflects the formation and growth of clusters of fragile water for changing to the strong water. The vitrification of water in micropores around 200 K was observed by (2)H NMR. Above 200 K, the correlation time of the rotation of water in micropores exhibited non-Arrhenius behavior, which is correlated with the gradual decrease in the mobility of water due to the growth of hydrogen bonding, forming low density water before vitrification. After vitrification, the activation energy of the rotation of water in micropores was 25-33 kJ mol(-1), which was similar to that in ice Ih for all samples. The freedom of cluster formation and water rotation increased with the increasing the pore size.

Protective effect of lactoferrin on acute acid reflux-induced esophageal mucosal damage.

BACKGROUND/AIMS: The natural immunomodulator lactoferrin is known to possess anti-inflammatory effects. However, there have been no studies examining the mode of action of lactoferrin in protecting the esophageal mucosa against damage. We investigated the effect of lactoferrin on gastric acid secretion and in protecting against acute acid reflux-induced esophagitis in rats. METHODOLOGY: Male Wistar rats aged 8 weeks, weighing 210-240 g, were used for all the experiments. A gastric perfusion system was installed using the method of Ghosh et al. Lactoferrin was administered once via the caudate vein, starting 24 hours before an acute acid reflux (treatment mode), or saline (control). Statistical comparison of the parameters between the two test conditions was performed. RESULTS: No significant differences in basal or stimulated gastric acid secretion, or in the serum gastrin level were observed between the two test conditions. Esophageal damage was attenuated by lactoferrin in a dose-dependent manner, as reflected by the improvement in the esophageal tissue weight and macroscopic scores. Significant reductions in the histological scores, myeloperoxidase activity and the levels of proinflammatory cytokines, tumor necrosis factor-α and interleukin-1ß were also observed following lactoferrin administration. CONCLUSIONS: We concluded that lactoferrin exerts a protective effect against acute acid reflux-induced esophageal damage in rats.

Correlation between gastric transit time measured by video capsule endoscopy and gastric emptying determined by the continuous real-time 13C breath test (BreathID system).

BACKGROUND/AIMS: The aim of this study was to determine the possible existence of a correlation between the gastric transit time (GTT) measured by video capsule endoscopy (VCE) and the parameters of gastric emptying determined using 13C breath test (BreathID system). METHODS: Eight healthy male volunteers participated in this randomized, two-way crossover study. The subjects were randomly assigned to undergo VCE using the PillCam SB capsule endoscopy system or the 13C breath test for 4 hours after a test meal (400 kcal per 400 mL) containing 100 mg of 13C acetic acid administered after overnight fasting. The VCE images were analyzed and the GTT was determined using the proprietary RAPID software. The parameters, namely T lag, T 1/2 and GEC were calculated using the Oridion Research Software (ß version). The GTT measured by VCE and the parameters of gastric emptying were compared statistically. RESULTS: No significant correlation was observed between the GTT and T lag (p = 0.5263), T 1/2 (p = 0.4100) or GEC (p = 0.2410), as determined by calculation of the Spearman's rank correlation coefficient. CONCLUSIONS: GTT measured by VCE cannot serve as asubstitute for the gastric emptying time measured bythe 13C breath test.

Stage IV gastric adenocarcinoma with enteroblastic differentiation with 5-year relapse-free survival after D2 gastrectomy and chemotherapy: A case report.

BACKGROUND: Gastric adenocarcinoma with enteroblastic differentiation (GACED), a rare subtype of gastric cancer, is associated with a more aggressive behavior than conventional gastric adenocarcinomas. We report a rare case of stage IV GACED treated with D2 gastrectomy and postoperative chemotherapy. CASE PRESENTATION: A 39-year-old woman with acute upper abdominal pain immediately underwent surgery for gastric perforation. Afterward she was diagnosed with adenocarcinoma of the pylorus. D2 gastrectomy was performed and the final pathological diagnosis was stage IV GACED with positive peritoneal cytology. Postoperative chemotherapy was initiated with S1 plus oxaliplatin for 1 year, which was ceased thereafter to enhance her quality of life. The patient survived more than 5 years without relapse after gastrectomy. CONCLUSIONS: Stage IV GACED, determined by positive spalt-like transcription factor 4, can be successfully treated with surgery and chemotherapy.

Predicting and analyzing organic reaction pathways by combining machine learning and reaction network approaches.

A learning model is proposed that predicts both products and reaction pathways by combining machine learning and reaction network approaches. By training 50 fundamental organic reactions, the learning model predicted the products and pathways of 35 test reactions with a top-5 accuracy of 68.6%. The model identified the key fragment structures of the intermediates and could be classified as several basic reaction rules in the context of organic chemistry, such as the Markovnikov rule.

N-Heterocyclic Carbene-Catalyzed Chemoselective Monoacylation of 1,n-Linear Diols.

This paper discusses the N-heterocyclic carbene (NHC)-catalyzed redox monoacylation of 1,n-linear diols using α-benzoyloxyaldehydes. The reactions afforded monoacylated diols in moderate to good selectivities and chemical yields. Our original NHC bearing a pyridine moiety plays an important role in achieving good chemoselectivities. A wide range of 1,n-linear diols were successfully applied to this reaction.

Proton Conduction Mechanism for Anhydrous Imidazolium Hydrogen Succinate Based on Local Structures and Molecular Dynamics.

Anhydrous organic crystalline materials incorporating imidazolium hydrogen succinate (Im-Suc), which exhibit high proton conduction even at temperatures above 100 °C, are attractive for elucidating proton conduction mechanisms toward the development of solid electrolytes for fuel cells. Herein, quantum chemical calculations were used to investigate the proton conduction mechanism in terms of hydrogen-bonding (H-bonding) changes and restricted molecular rotation in Im-Suc. The local H-bond structures for proton conduction were characterized by vibrational frequency analysis and compared with corresponding experimental data. The calculated potential energy surface involving proton transfer (PT) and imidazole (Im) rotational motion showed that PT between Im and succinic acid was a rate-limiting step for proton transport in Im-Suc and that proton conduction proceeded via the successive coupling of PT and Im rotational motion based on a Grotthuss-type mechanism. These findings provide molecular-level insights into proton conduction mechanisms for Im-based (or -incorporated) H-bonding organic proton conductors.