Oral Breathing Facilitates Endoscopic Operability Compared With Nasal Breathing in Peroral Endoscopy: A Randomized Controlled Trial.

INTRODUCTION: Unsedated peroral endoscopy, including ultrathin endoscopy (UE) and conventional endoscopy (CE), is feasible in clinical practice but requires improved endoscopic operability and patient tolerance. Currently, the impact of the breathing method on these factors remains unclear. We conducted the first randomized controlled trial comparing oral breathing (OB) and nasal breathing (NB) during both UE and CE to assess their influence. METHODS: About 252 eligible patients undergoing CE or UE were randomly assigned to OB or NB groups. Endoscopists and patients rated endoscopic operability and patient tolerance using a 100-mm visual analog scale. Visibility from the oral cavity to the middle pharynx was recorded. RESULTS: OB led to a higher rate of improved visibility from the oral cavity to the middle pharynx compared with NB, ranging from 79.3% to 81.0%. Multivariate correlation analyses showed significantly lower visual analog scale scores for endoscopic operability with OB compared with NB in both UE and CE groups ( P < 0.05). No significant differences were found in the overall evaluation of patient tolerance between OB and NB groups in UE and CE, whereas the smaller diameter of UE exhibited better patient tolerance compared with CE. Discriminant analysis comparing endoscope types and breathing methods revealed that UE with OB outperformed other combinations in the overall evaluation of endoscopic operability and patient tolerance ( P < 0.05). DISCUSSION: OB facilitates endoscopic operability compared with NB in peroral endoscopy. UE with OB is recommended as the preferred choice for unsedated peroral endoscopy in daily practice.

Controlling the Formation of Polyhedral Block Copolymer Nanoparticles: Insights from Process Variables and Dynamic Modeling.

This study delves into the formation of nanoscale polyhedral block copolymer particles (PBCPs) exhibiting cubic, octahedral, and variant geometries. These structures represent a pioneering class that has never been fabricated previously. PBCP features distinct variations in curvature on the outer surface, aligning with the edges and corners of polyhedral shapes. This characteristic sharply contrasts with previous block copolymers (BCPs), which displayed a smooth spherical surface. The emergence of these cornered morphologies presents an intriguing and counterintuitive phenomenon and is linked to process parameters, such as evaporation rates and initial concentration, while keeping other variables constant. Using a system of coupled Cahn-Hillard (CCH) equations, we uncover the mechanisms driving polyhedral particle formation, emphasizing the importance of controlling relaxation parameters for shape variable u and microphase separation v. This unconventional approach, differing from traditional steepest descent method, allows for precise control and diverse polyhedral particle generation. Accelerating the shape variable u proves crucial for expediting precipitation and aligns with experimental observations. Employing the above theoretical model, we achieve shape predictions for particles and the microphase separation within them, which overcomes the limitations of ab initio computations. Additionally, a numerical stability analysis discerns the transient nature versus local minimizer characteristics. Overall, our findings contribute to understanding the complex interplay between process variables and the morphology of polyhedral BCP nanoparticles.

Liquid Biopsy for Pancreatic Cancer by Serum Extracellular Vesicle-Encapsulated Long Noncoding RNA HEVEPA.

OBJECTIVES: The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)-encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs. MATERIALS AND METHODS: Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR. RESULTS: Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA , in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA , which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC , which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA , HULC , or CA19-9 alone. CONCLUSIONS: Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

Nasal breathing is superior to oral breathing when performing and undergoing transnasal endoscopy: a randomized trial.

BACKGROUND : Transnasal endoscopy presents a technical difficulty when inserting the flexible endoscope. It is unclear whether a particular breathing method is useful for transnasal endoscopy. Therefore, we conducted a prospective randomized controlled trial to compare endoscopic operability and patient tolerance between patients assigned to nasal breathing or oral breathing groups. METHODS : 198 eligible patients were randomly assigned to undergo transnasal endoscopy with nasal breathing or with oral breathing. Endoscopists and patients answered questionnaires on the endoscopic operability and patient tolerance using a 100-mm visual analog scale ranging from 0 (non-existent) to 100 (most difficult/unbearable). The visibility of the upper-middle pharynx was recorded. RESULTS : Patient characteristics did not differ significantly between the groups. Nasal breathing showed a higher rate of good visibility of the upper-middle pharynx than oral breathing (91.9 % vs. 27.6 %; P < 0.001). Nasal breathing showed lower mean [SD] scores than oral breathing in terms of overall technical difficulty (21.0 [11.4] vs. 35.4 [15.0]; P < 0.001). Regarding patient tolerance, nasal breathing showed lower scores than oral breathing for overall discomfort (22.1 [18.8] vs. 30.5 [20.9]; P = 0.004) and other symptoms, including nasal and throat pain, choking, suffocating, gagging, belching, and bloating (all P < 0.05). The pharyngeal bleeding rate was lower in the nasal breathing group than in the oral breathing group (0 % vs. 9.2 %; P = 0.002). CONCLUSIONS : Nasal breathing is superior to oral breathing for those performing and undergoing transnasal endoscopy. Nasal breathing led to good visibility of the upper-middle pharynx, improved endoscopic operability, and better patient tolerance, and was safer owing to decreased pharyngeal bleeding.

High-Quality SiO2/O-Terminated Diamond Interface: Band-Gap, Band-Offset and Interfacial Chemistry.

Silicon oxide atomic layer deposition synthesis development over the last few years has open the route to its use as a dielectric within diamond electronics. Its great band-gap makes it a promising material for the fabrication of diamond-metal-oxide field effects transistor gates. Having a sufficiently high barrier both for holes and electrons is mandatory to work in accumulation and inversion regimes without leakage currents, and no other oxide can fulfil this requisite due to the wide diamond band-gap. In this work, the heterojunction of atomic-layer-deposited silicon oxide and (100)-oriented p-type oxygen-terminated diamond is studied using scanning transmission electron microscopy in its energy loss spectroscopy mode and X-ray photoelectron spectroscopy. The amorphous phase of silicon oxide was successfully synthesized with a homogeneous band-gap of 9.4 eV. The interface between the oxide and diamond consisted mainly of single- and double-carbon-oxygen bonds with a low density of interface states and a straddling band setting with a 2.0 eV valence band-offset and 1.9 eV conduction band-offset.

Computer-aided classification of hepatocellular ballooning in liver biopsies from patients with NASH using persistent homology.

BACKGROUND AND OBJECTIVE: Hepatocellular ballooning is an important histological parameter in the diagnosis of nonalcoholic steatohepatitis (NASH), and it is considered to be a morphological pattern that indicates the severity and the progression to cirrhosis and liver-related deaths. There remains uncertainty about the pathological criteria for evaluating the spectrum of non-alcoholic fatty liver disease (NAFLD) in liver biopsies. We introduce persistence images as novel mathematical descriptors for the classification of ballooning degeneration in the pathological diagnosis. METHODS: We implemented and tested a topological data analysis methodology combined with linear machine learning techniques and applied this to the classification of tissue images into NAFLD subtypes using Matteoni classification in liver biopsies. RESULTS: Digital images of hematoxylin- and eosin-stained specimens with a pathologist's visual assessment were obtained from 79 patients who were clinically diagnosed with NAFLD. We obtained accuracy rates of more than 90% for the classification between NASH and non-NASH NAFLD groups. The highest area under the curve from the receiver operating characteristic analysis was 0.946 for the classification of NASH and NAFL2 (type 2 of Matteoni classification), when both 0- and 1-dimensional persistence images were used. CONCLUSIONS: Our methodology using persistent homology provides quantitative measurements of the topological features in liver biopsies of NAFLD groups with considerable accuracy.

Ashura Particles: Experimental and Theoretical Approaches for Creating Phase-Separated Structures of Ternary Blended Polymers in Three-Dimensionally Confined Spaces.

Unique morphologies were found in binary and ternary polymer blended particles, including Ashura-type phase separation, which has three different polymer components on the particle surface. The morphologies of phase-separated structures in the binary polymer blended particles are discussed in terms of the surface tensions of the blended polymers. Structural control of ternary polymer blended particles was achieved based on the combination of polymers by examining binary polymer blended particles. A theoretical approach based on the Cahn-Hilliard equations gives identical morphologies with the experimental results. This work opens the way to creating polymer particles with sophisticated nanostructures by controlling their morphologies as predicted by theoretical simulations.

Betti number ratios as quantitative indices for bone morphometry in three dimensions.

BACKGROUND AND OBJECTIVE: Computational homology is an emerging mathematical tool for characterizing shapes of data. In this work, we present a methodology using computational homology for obtaining quantitative measurements of the connectivity in bone morphometry. We introduce the Betti number ratios as novel morphological descriptor for the classification of bone fine structures in three dimensions. METHODS: A total of 51 Japanese white rabbits were used to investigate the connectivity of bone trabeculae after the administration of alendronate in a tendon graft model in rabbits. They were divided into a control group C and an experimental group A. Knee joints specimens were harvested for examination of their bone trabecular structure by micro-CT. Applying the computational homology software to the reconstructed 3D image data, we extract the morphological feature of a steric bone structure as the Betti numbers set (ß0, ß1, ß2). The zeroth Betti number ß0 indicates the number of the connected components corresponding to isolated bone fragments. The first and second Betti numbers, ß1 and ß2, indicate the numbers of open pores and closed pores of bone trabeculae, corresponding to a 2D empty space enclosed by a 1D curve and a 3D empty space enclosed by a 2D surface, respectively. RESULTS: We define the Betti number ratios ß1/ß0 and ß2/ß0 to better distinguish the two groups A and C in the scatter plots. Testing the discriminant function line for 29 data points of A (22 data points of C), the 17 points (resp. 18 points) are correctly classified into group A (resp. C). The accuracy rate is 35/51. The classification results in terms of the Betti number ratios are consistent with the histomorphometric measurements observed by medical doctors. CONCLUSIONS: This study is the first application of computational homology to bone morphometry in three dimensions. We show the mathematical basis of the Betti numbers index which are useful in a statistical description of the topological features of sponge-like structures. The potential benefits associated with our method include both improved quantification and reproducibility for the stereology.

Transformation of Block Copolymer Nanoparticles from Ellipsoids with Striped Lamellae into Onionlike Spheres and Dynamical Control via Coupled Cahn-Hilliard Equations.

Annealing of block copolymers has become a tool of great importance for the reconfiguration of nanoparticles. Here, we present the experimental results of annealing block copolymer nanoparticles and a theoretical model to describe the morphological transformation of ellipsoids with striped lamellae into onionlike spheres. A good correspondence between the experimental findings and predictions of the model was observed. The model based on finding the steepest direction of descent of an appropriate free energy leads to a set of Cahn-Hilliard equations that correctly describe the dynamical transformation of striped ellipsoids into onionlike spheres and reverse onionlike particles, regardless of the nature of the annealing process. This universality makes it possible to describe a variety of experimental conditions involving nanoparticles underlying a heating process. A notable advantage of the proposed approach is that it enables selective control of the interaction between the confined block copolymer and the surrounding medium. This feature endows the model with a great versatility to enable the reproduction of several combined effects of surfactants in diverse conditions, including cases with reverse affinities for the block copolymer segments. A phase diagram to describe a variety of morphologies is presented. We employ the relationship between the temperature-dependent Flory-Huggins parameter and the width of the interfaces to account for changes in temperature due to the heating process. Simulation results correctly show how the transformation evolves as the temperature increases. This increment in temperature corresponds to progressively smaller values of the interfacial width. We anticipate that the proposed approach will facilitate the design and more precise control of experiments involving various kinds of annealing processes.

Persistent homology index as a robust quantitative measure of immunohistochemical scoring.

Immunohistochemical data (IHC) plays an important role in clinical practice, and is typically gathered in a semi-quantitative fashion that relies on some degree of visual scoring. However, visual scoring by a pathologist is inherently subjective and manifests both intra-observer and inter-observer variability. In this study, we introduce a novel computer-aided quantification methodology for immunohistochemical scoring that uses the algebraic concept of persistent homology. Using 8 bit grayscale image data derived from 90 specimens of invasive ductal carcinoma of the breast, stained for the replicative marker Ki-67, we computed homology classes. These were then compared to nuclear grades and the Ki-67 labeling indices obtained by visual scoring. Three metrics for IHC staining were newly defined: Persistent Homology Index (PHI), center coordinates of positive and negative groups, and the sum of squares within groups (WSS). This study demonstrates that PHI, a novel index for immunohistochemical labeling using persistent homology, can produce highly similar data to that generated by a pathologist using visual evaluation. The potential benefits associated with our novel technology include both improved quantification and reproducibility. Since our method reflects cellularity and nuclear atypia, it carries a greater quantity of biologic data compared to conventional evaluation using Ki-67.

Correction: Frustrated phases under three-dimensional confinement simulated by a set of coupled Cahn-Hilliard equations.

Correction for 'Frustrated phases under three-dimensional confinement simulated by a set of coupled Cahn-Hilliard equations' by Edgar Avalos et al., Soft Matter, 2016, 12, 5905-5914.

Frustrated phases under three-dimensional confinement simulated by a set of coupled Cahn-Hilliard equations.

We numerically study a set of coupled Cahn-Hilliard equations as a means to find morphologies of diblock copolymers in three-dimensional spherical confinement. This approach allows us to find a variety of energy minimizers including rings, tennis balls, Janus balls and multipods among several others. Phase diagrams of confined morphologies are presented. We modify the size of the interface between microphases to control the number of holes in multipod morphologies. Comparison to experimental observation by transmission electron microtomography of multipods in polystyrene-polyisoprene diblock copolymers is also presented.

Florigen distribution determined by a source-sink balance explains the diversity of inflorescence structures in Arabidopsis.

The ability to continue flowering after loss of inductive environmental cues that trigger flowering is termed floral commitment. Reversible transition involving a switch from floral development back to vegetative development has been found in Arabidopsis mutants and many plant species. Although the molecular basis for floral commitment remains unclear, recent studies suggest that the persistent activity of FLOWERING LOCUS T (FT) at inflorescences is required for floral commitment in Arabidopsis thaliana. Because FT encodes a mobile signal, florigen, which is generally transported from leaves to meristems through the phloem, understanding the transportation dynamics of FT is required to explore the role of FT on floral commitment. Here we developed a transportation model of leaf- and inflorescence-derived florigen and sucrose based on pressure-flow hypothesis. Depending on the demanded level of florigen supply for floral commitment of each floral meristem, the model predicted the change in inflorescence pattern from stable commitment to flower, transient flowering, and complete reversion. FT activity in inflorescence partly suppressed floral reversion, but complete suppression was achieved only when inflorescence became a source of sucrose. This finding highlights the importance of monitoring the spatio-temporal sucrose distribution and floral stimulus to understand inflorescence development mechanism.

Rotational motion of traveling spots in dissipative systems.

What is the origin of rotational motion? An answer is presented through the study of the dynamics for spatially localized spots near codimension 2 singularity consisting of drift and peanut instabilities. The drift instability causes a head-tail asymmetry in spot shape, and the peanut one implies a deformation from circular to peanut shape. Rotational motion of spots can be produced by combining these instabilities in a class of three-component reaction-diffusion systems. Partial differential equations dynamics can be reduced to a finite-dimensional one by projecting it to slow modes. Such a reduction clarifies the bifurcational origin of rotational motion of traveling spots in two dimensions in close analogy to the normal form of 1:2 mode interactions.

Onset of unidirectional pulse propagation in an excitable medium with asymmetric heterogeneity.

Heterogeneity is one of the most important and ubiquitous types of external perturbations in dissipative systems. To know the behaviors of pulse waves in such media is closely related to studying the collision process between the pulse and the heterogeneity-induced-ordered pattern. In particular, we focus on unidirectional propagation of pulses in a medium with an asymmetric bump heterogeneity. This topic has attracted much interest recently with respect to potential computational aspects of chemical pulse propagation as well as with respect to pulse propagation in biological signal processing. We employ a three-component reaction-diffusion system with one activator and two inhibitor species to illustrate these issues. The reduced dynamics near a drift bifurcation describes the phenomena in the full partial differential equations by ordinary differential equations. Such a reduced dynamics is able to capture unidirectional propagation properties of pulses near an asymmetric heterogeneity in a qualitatively correct way. A remarkable feature is that such unidirectional behavior is linked to the imperfection of global bifurcation structure and the resulting asymmetric locations of critical points.

Topological validation of morphology modeling by extended reverse Monte Carlo analysis.

A combination of reverse Monte Carlo (RMC) and computational homology is examined as a useful approach in connecting scattering experiments to mathematics for 3D morphology modeling. We develop a different method of morphology modeling from multiple two-dimensional (2D) scattering patterns of structure functions by RMC technique using coarse-grained particles. We perform RMC analysis for multiple 2D scattering patterns of the configuration generated from the surface equation of double gyroid morphology. Homology analysis enables us to classify complex three-dimensional morphologies by incorporating topologically invariant quantities, the so-called Betti numbers. It is demonstrated that RMC analysis reconstructs the DG morphology from multiple 2D scattering patterns.

Dynamics of traveling pulses in heterogeneous media.

One of the fundamental issues of pulse dynamics in dissipative systems is clarifying how the heterogeneity in the media influences the propagating manner. Heterogeneity is the most important and ubiquitous type of external perturbation. We focus on a class of one-dimensional traveling pulses, the associated parameters of which are close to drift and/or saddle-node bifurcations. The advantage in studying the dynamics in such a class is twofold: First, it gives us a perfect microcosm for the variety of outputs in a general setting when pulses encounter heterogeneities. Second, it allows us to reduce the original partial differential equation dynamics to a tractable finite-dimensional system. Such pulses are sensitive when they run into heterogeneities and show rich responses such as annihilation, pinning, splitting, rebound, as well as penetration. The reduced ordinary differential equations (ODEs) explain all these dynamics and the underlying bifurcational structure controlling the transitions among different dynamic regimes. It turns out that there are hidden ordered patterns associated with the critical points of ODEs that play a pivotal role in understanding the responses of the pulse; in fact, the depinning of pulses can be explained in terms of global bifurcations among those critical points. We focus mainly on a bump and periodic types of heterogeneity, however our approach is also applicable to general cases. It should be noted that there appears to be spatio-temporal chaos for a periodic type of heterogeneity when its period becomes comparable with the size of the pulse.

Heterogeneity-induced defect bifurcation and pulse dynamics for a three-component reaction-diffusion system.

We consider the dynamics when traveling pulses encounter heterogeneities in a three-component reaction diffusion system of one-activator-two-inhibitor type, which typically arises as a qualitative model of a gas-discharge system. We focused on the case where one of the kinetic coefficients changes similar to a smoothed step function, which is basic for more general heterogeneity as in periodic or random media. Since the heterogeneity is introduced to the kinetic part in an additive way, it causes the system to produce various types of localized structures smoothing the jump heterogeneity called the defects at the jump point, which makes a sharp contrast with the multiplicative heterogeneous case for the Gray-Scott model. The main issue is to study the collision dynamics between traveling pulses and defects, and show that their global bifurcation structure plays a key role in clarifying the underlying mechanism. Five outputs are observed after collisions including annihilation, rebound, and pinning. Unstable steady states are identified as separators between two different dynamic regimes: penetration and rebound, the role of which is very close to that of scattors arising in collision process. An organizing center producing the traveling pulses, defects, and scattors via unfolding with respect to the parameters is also presented.

Scattering of traveling spots in dissipative systems.

One of the fundamental questions for self-organization in pattern formation is how spatial periodic structure is spontaneously formed starting from a localized fluctuation. It is known in dissipative systems that splitting dynamics is one of the driving forces to create many particle-like patterns from a single seed. On the way to final state there occur many collisions among them and its scattering manner is crucial to predict whether periodic structure is realized or not. We focus on the colliding dynamics of traveling spots arising in a three-component system and study how the transition of scattering dynamics is brought about. It has been clarified that hidden unstable patterns called "scattors" and their stable and unstable manifolds direct the traffic flow of orbits before and after collisions. The collision process in general can be decomposed into several steps and each step is controlled by such a scattor, in other words, a network among scattors forms the backbone for scattering dynamics. A variety of input-output relations comes from the complexity of the network as well as high Morse indices of the scattor. The change of transition manners is caused by the switching of the network from one structure to another, and such a change is caused by the singularities of scattors. We illustrate a typical example of the change of transition caused by the destabilization of the scattor. A new instability of the scattor brings a new destination for the orbit resulting in a new input-output relation, for instance, Hopf instability for the scattor of peanut type brings an annihilation.

Phase-dependent output of scattering process for traveling breathers.

Scattering process between one-dimensional traveling breathers (TBs), i.e., oscillatory traveling pulses, for the complex Ginzburg-Landau equation (CGLE) with external forcing and a three-component activator-substrate-inhibitor model are studied. The input-output relation depends in general on the phase of two TBs at collision point, which makes a contrast to the case for the steady traveling pulses. A hidden unstable solution called the scattor plays a crucial role to understand the scattering dynamics. Stable and unstable manifolds of the scattor direct the traffic flows of the scattering process. A transition point of the input-output relation in a parameter space such as from preservation to annihilation corresponds to when the orbit crosses the stable manifold of the scattor. The phase dependency of input-output relation comes from the fact that the profiles at collision point make a loop parametrized by the phase and it traverses the stable manifold of the scattor. A global bifurcation viewpoint is quite useful not only to understand how TBs emerge but also to detect scattors. It turns out that the scattor for the CGLE (respectively the three-component system) becomes an unstable time-periodic (respectively stationary) solution.