Assessing risk of recurrent small bowel obstruction after non-operative management in patients with history of intra-abdominal surgery: a population-based comprehensive analysis in Taiwan.

BACKGROUND: Despite a significant 30% ten-year readmission rate for SBO patients, investigations into recurrent risk factors after non-operative management are scarce. The study aims to generate a risk factor scoring system, the 'Small Bowel Obstruction Recurrence Score' (SBORS), predicting 6-month recurrence of small bowel obstruction (SBO) after successful non-surgical management in patients who have history of intra-abdominal surgery. METHODS: We analyzed data from patients aged ≥ 18 with a history of intra-abdominal surgery and diagnosed with SBO (ICD-9 code: 560, 568) and were successful treated non-surgically between 2004 and 2008. Participants were divided into model-derivation (80%) and validation (20%) group. RESULTS: We analyzed 23,901 patients and developed the SBORS based on factors including the length of hospital stay > 4 days, previous operations > once, hemiplegia, extra-abdominal and intra-abdominal malignancy, esophagogastric surgery and intestino-colonic surgery. Scores > 2 indicated higher rates and risks of recurrence within 6 months (12.96% vs. 7.27%, OR 1.898, p < 0.001 in model-derivation group, 12.60% vs. 7.05%, OR 1.901, p < 0.001 in validation group) with a significantly increased risk of mortality and operative events for recurrent episodes. The SBORS model demonstrated good calibration and acceptable discrimination, with an area under curve values of 0.607 and 0.599 for the score generation and validation group, respectively. CONCLUSIONS: We established the effective 'SBORS' to predict 6-month SBO recurrence risk in patients who have history of intra-abdominal surgery and have been successfully managed non-surgically for the initial obstruction event. Those with scores > 2 face higher recurrence rates and operative risks after successful non-surgical management.

Calculation of CYP450 protein-ligand binding and dissociation free energy paths.

The function of an enzyme depends on its dynamic structure, and the catalytic mechanism has long been an active focus of research. The principle for interpreting protein selectivity and fidelity stems from optimization of the active site upon protein-substrate complexation, i.e., a lock-and-key configuration, on which most protein-substrate molecule binding recognition, and hence drug discovery, relies. Yet another thought has been to incorporate the protein folding interior tunnels for stereo- and regio-selectivity along the protein-substrate or protein-ligand/inhibitor binding process. Free energy calculations provide valuable information for molecular recognition and protein-ligand binding dynamics and kinetics. In this study, we focused on the kinetics of cytochrome P450 proteins (CYP450s) and the protein interior tunnel structure-dynamics relationship in terms of the substrate binding and leaving mechanism. A case in point is given by the prostaglandin H2 (PGH2) homologous isomerase of prostacyclin synthase. To calculate the reactant and product traversing the tunnels to and from the heme site, the free energy paths and tunnel potentials of mean force are constructed from steered molecular dynamics simulations and adaptive basing force umbrella sampling simulations. We explore the binding tunnels and critical residue lining characteristics for the ligand traverse and the underlying mechanism of CYP450 activity. Our theoretical analysis provides insights into the decisive role of the substrate tunnel binding process of the CYP450 mechanism and may be useful in drug design and protein engineering contexts.

Probing Interactions between Metal-Organic Frameworks and Freestanding Enzymes in a Hollow Structure.

It has been reported that the biological functions of enzymes could be altered when they are encapsulated in metal-organic frameworks (MOFs) due to the interactions between them. Herein, we probed the interactions of catalase in solid and hollow ZIF-8 microcrystals. The solid sample with confined catalase is prepared through a reported method, and the hollow sample is generated by hollowing the MOF crystals, sealing freestanding enzymes in the central cavities of hollow ZIF-8. During the hollowing process, the samples were monitored by small-angle X-ray scattering (SAXS) spectroscopy, electron microscopy, powder X-ray diffraction (PXRD), and nitrogen sorption. The interfacial interactions of the two samples were studied by infrared (IR) and fluorescence spectroscopy. IR study shows that freestanding catalase has less chemical interaction with ZIF-8 than confined catalase, and a fluorescence study indicates that the freestanding catalase has lower structural confinement. We have then carried out the hydrogen peroxide degradation activities of catalase at different stages and revealed that the freestanding catalase in hollow ZIF-8 has higher activity.

Calibration of a compact XUV soft X-ray monochromator with a digital autocollimator in situ.

A digital autocollimator of resolution 0.1 µrad (0.02 arcsec) serves as a handy correction tool for calibrating the angular uncertainty during angular and lateral movements of gratings inside a monochromator chamber under ultra-high vacuum. The photon energy dispersed from the extreme ultraviolet (XUV) to the soft X-ray region of the synchrotron beamline at the Taiwan Light Source was monitored using molecular ionization spectra at high resolution as energy references that correlate with the fine angular steps during grating rotation. The angular resolution of the scanning mechanism was <0.3 µrad, which results in an energy shift of 80 meV at 867 eV. The angular uncertainties caused by the lateral movement during a grating exchange were decreased from 2.2 µrad to 0.1 µrad after correction. The proposed method provides a simple solution for on-site beamline diagnostics of highly precise multi-axis optical manipulating instruments at synchrotron facilities and in-house laboratories.

A plug-and-measure diagnostic tool for flux, resolution and beam size of a soft X-ray beamline.

A compact multi-functional diagnostic tool has been installed for commissioning beamlines at the Taiwan Light Source. For a photon beam, the instrument can measure the photon flux, energy resolution and beam size, consecutively with a photodiode or gold mesh, a windowless gas cell and a movable fluorescence screen viewport. Two gratings with ruling densities of 350 and 1000 lines mm(-1) and dispersing photons of energies from 80 to 1200 eV were calibrated with a photon flux of 10(11) photon s(-1) at slit openings of 50 µm × 50 µm; a maximum resolving power of greater than 10000 was certified with an absorption spectra of gaseous samples. Pressure differences over four orders of magnitude were achieved between the ion chamber and the flux measurement chamber with a single capillary differential pumping stage. A sequence of beam profiles was measured by moving continuously in the vicinity of the nominal focal positions. This tool is useful in commissioning or trouble-shooting at most beamlines in a synchrotron facility.

Adversarial Exposure Attack on Diabetic Retinopathy Imagery Grading.

Diabetic Retinopathy (DR) is a leading cause of vision loss around the world. To help diagnose it, numerous cutting-edge works have built powerful deep neural networks (DNNs) to automatically grade DR via retinal fundus images (RFIs). However, RFIs are commonly affected by camera exposure issues that may lead to incorrect grades. The mis-graded results can potentially pose high risks to an aggravation of the condition. In this paper, we study this problem from the viewpoint of adversarial attacks. We identify and introduce a novel solution to an entirely new task, termed as adversarial exposure attack, which is able to produce natural exposure images and mislead the state-of-the-art DNNs. We validate our proposed method on a real-world public DR dataset with three DNNs, e.g., ResNet50, MobileNet, and EfficientNet, demonstrating that our method achieves high image quality and success rate in transferring the attacks. Our method reveals the potential threats to DNN-based automatic DR grading and would benefit the development of exposure-robust DR grading methods in the future.

Decoding the Biomimetic Mineralization of Metal-Organic Frameworks in Water.

This study unveils the "green" metal-organic framework (MOF) structuring mechanism by decoding proton transfer in water during ZIF-8 synthesis. Combining in situ small- to wide-angle X-ray scattering, multiscale simulations, and quantum calculations, we reveal that the ZIF-8 early-stage nucleation and crystallization process in aqueous solution unfolds in three distinct stages. In stage I, imidazole ligands replace water in zinc-water cages, triggering an "acidity flip" that promotes proton transfer. This leads to the assembly of structures from single zinc ions to 3D amorphous cluster nuclei. In stage II, amorphous nuclei undergo a critical transformation, evolving into crystalline nuclei and subsequently forming mesoscale-ordered structures and crystallites. The process proceeds until the amorphous precursors are completely consumed, with the transformation kinetics governed by an energy barrier that determines the rate-limiting step. In stage III, stable crystallite nanoparticles form in solution, characterized by a temperature-dependent thermal equilibrium of molecular interactions at the crystal-solution interface. Beyond these core advancements, we explore the influence of encapsulated pepsin and nonencapsulated lysozyme on ZIF-8 formation, finding that their amino acid proton transfer capacity and concentration influence the resulting biomolecule-MOF composite's shape and encapsulation efficiency. The findings contribute to understanding the molecular mechanisms behind biomimetic mineralization and have potential implications for engineering proteins within amorphous MOF nuclei as protein embryo growth sites.

Exploring Enzyme Encapsulation Efficiency in MOFs Using Eco-friendly Approaches.

The encapsulation of protein enzymes in metal-organic frameworks (MOFs) has been recognized as an effective enzyme immobilization approach. In this study, we demonstrated the influence of enzyme amount and the isoelectric points (pI) of different enzymes on the enzyme loading capacity in both mechanochemical (ball-milling) and water-based approaches. We found that increasing enzyme amounts enhances MOF enzyme loading without compromising activity, while the MOF shell protects encapsulated enzymes from proteinase K degradation through its size-sheltering mechanism. However, an excess of enzymes can hinder the formation of ZIF-90. Moreover, enzymes with low pI values (e.g., catalase, pI 5.4) facilitate encapsulation in MOFs, whereas enzymes with high pI values (e.g., lysozyme, pI 11.35) are more challenging to encapsulate. The simulation results revealed that increasing the enzyme amounts and pI values raises the activation energy necessary for MOF formation. This study highlights the crucial role of enzyme properties in the encapsulation process within MOFs, providing valuable insights for fabricating enzyme-MOF biocomposites for diverse applications, such as protein drug delivery.

Mortality Prediction Model before Surgery for Acute Mesenteric Infarction: A Population-Based Study.

Surgery for acute mesenteric infarction (AMI) is associated with high mortality. This study aimed to generate a mortality prediction model to predict the 30-day mortality of surgery for AMI. We included patients ≥18 years who received bowel resection in treating AMI and randomly divided into the derivation and validation groups. After multivariable analysis, the 'Surgery for acute mesenteric infarction mortality score' (SAMIMS) system was generated and was including age >62-year-old (3 points), hemodialysis (2 points), congestive heart failure (1 point), peptic ulcer disease (1 point), diabetes (1 point), cerebrovascular disease (1 point), and severe liver disease (4 points). The 30-day-mortality rates in the derivation group were 4.4%, 13.4%, 24.5%, and 32.5% among very low (0 point), low (1−3 point(s)), intermediate (4−6 points), and high (7−13 points)-risk patients. Compared to the very-low-risk group, the low-risk (OR = 3.332), intermediate-risk (OR = 7.004), and high-risk groups (OR = 10.410, p < 0.001) exhibited higher odds of 30-day mortality. We identified similar results in the validation group. The areas under the ROC curve were 0.677 and 0.696 in the derivation and validation groups. Our prediction model, SAMIMS, allowed for the stratification of the patients' 30-day-mortality risk of surgery for acute mesenteric infarction.

Metrology for optical components of Taiwan Photon Source beamlines.

To ensure the high performance of beamlines in Taiwan Photon Source, the metrology of the beamline optical components is essential to realize the theoretical optical simulation. The design and performance of a long-trace profiler (LTP) with moving optical head is described. A LTP is used as a metrological tool for the assembly and correction of optical components at the beamline. For a water-cooled mirror, a LTP serves to optimize the surface profile to a slope error of 0.1 µrad (rms) and adequate thermal conductance. To correct a bendable cooling mirror in a twisted condition, the sagittal slope is decreased by a screw adjustment through the LTP measurement. For the double-crystal monochromator (DCM) with flow-induced vibrations, we proposed an approach to stiffen the bellows hose partially inside the vacuum chamber. From an investigation of the vibrational spectra of the DCM before and after the treatment with the aid of the autocollimator, the current approach is confirmed to be an effective solution for suppression of vibration.

Development of a long trace profiler in situ at National Synchrotron Radiation Research Center.

To achieve an ultrahigh resolution of a beamline for soft X-rays at the Taiwan Photon Source (TPS), the profile of a highly precise grating is required at various curvatures. The slope error could be decreased to 0.1 µrad (rms) at a thermal load with a specially designed bender having 25 actuators. In the meantime, a long-trace profiler (LTP) was developed in situ to monitor the grating profile under a thermal load; it consists of a moving optical head, an air-bearing slide, an adjustable stand, and a glass viewport on the vacuum chamber. In the design of this system, a test chamber with an interior mirror was designed to simulate the chamber in the beamline. To prevent an error induced from a commercial viewport, a precision glass viewport (150CF, flatness 1/150 λ rms at 632.8 nm) was designed. The error induced from the slope error of the glass surface and the vacuum deformation was also simulated. The performance of the optical head of the LTP in situ (ISLTP) has been tested in the metrology laboratory. The sources of error of this LTP including the linearity and the glass viewport were corrected after the measurement. For the beamline measurement, an optical head was mounted outside the vacuum chamber; the measuring beam passed through the glass viewport to measure the grating profile in vacuum. The measurement of the LTP after correction of the above errors yielded a precision about 0.2 µrad (rms). In a preliminary test, an ISLTP was used to measure the grating profile at soft X-ray beamline TPS45A. The measured profile was for the bending mechanism to optimize the slope profile. From the measured energy spectrum, the slope error of the grating was estimated with software for optical simulation to be about 0.3 µrad (rms), consistent with our estimate of the ISLTP. In the future, it will be used to monitor the thermal bump under a large thermal load. In addition, an ISLTP was used to monitor the properties of optical elements-the twist and radius in the beamline during the installation phase.