Miracle-dz/UniFAR-FTUs huggingface dataset:
The Positive Predictive Value of Hip Fracture Diagnoses and Surgical Procedure Codes in the Danish Multidisciplinary Hip Fracture Registry and the Danish National Patient Registry

Aim The health-care databases may be a valuable source for epidemiological research in hip fracture surgery, if the diagnoses are valid. We examined the validity of hip fracture diagnoses and surgical procedure codes in the Danish Multidisciplinary Hip Fracture Registry (DMHFR) and the Danish National Patient Registry (DNPR) by calculating the positive predictive value (PPV). Methods We identified a random sample of 750 hip fracture patients registered in the DMHFR between 2014 and 2017. Diagnoses have been coded by the 10th revision of the International Classification of Diseases, while procedures have been coded by the Nordic Medico-Statistical Committee classification in the DNPR and directly transferred to the DMHFR. Using the surgical procedure description from the medical record as gold standard, we estimated the PPV of the hip fracture diagnoses and surgical procedure codes in the DMHFR and the DNPR with 95% confidence interval (CIs). Results The PPV was 90% (95% CI: 86%-93%) for fracture of the neck of femur, 92% (95% CI: 87%-95%) for trochanteric fracture, and 83% (95% CI: 78%-88%) for subtrochanteric fracture. Joining trochanteric and subtrochanteric fracture resulted in a PPV of 97% (95% CI: 95%-98%). Procedure codes had a PPV of 100% for primary prosthetic replacement and internal fixation with intramedullary nail, 96% (95% CI: 85%-99%) for internal fixation using screws alone, 91% (95% CI: 84%-96%) for internal fixation using plates and screws, and 89% (95% CI: 83%-94%) for internal fixation with other or combined methods. Stratifying by age group, gender, hospital type and calendar year of surgery showed similar results as the overall PPV estimates. Conclusion Our findings indicate a high quality of the hip fracture diagnoses and corresponding procedure codes in the DMHFR and the DNPR, with a majority of PPVs above 90%. Thus, the DMHFR and the DNPR are a valuable data source on hip fracture for epidemiological research.
Reverse vaccinology approach for the identification and characterization of outer membrane proteins of Shigella flexneri as potential cellular- and antibody-dependent vaccine candidates

Purpose In the developing world, bacillary dysentery is one of the most common communicable diarrheal infections. There are approximately 169 million cases of shigellosis reported worldwide. The disease is transmitted by a group of Gram-negative intracellular enterobacteria known as Shigella flexneri, S. sonnei, S. dysenteriae, and S. boydii. Conventional treatment regimens for Shigella have been less effective due to the development of resistant strains against antibiotics. Therefore, an effective vaccine for the long term control of Shigella transmission is urgently needed. Materials and Methods In this study, a reverse vaccinology approach was employed to identify most conserved and immunogenic outer membrane proteins (OMPs) of S. flexneri 2a. Results Five OMPs including fepA, ompC, nlpD_1, tolC, and nlpD_2 were identified as potential vaccine candidates. Protein-protein interactions analysis using STRING software (https://string-db.org/) revealed that five of these OMPs may potentially interact with other intracellular proteins which are involved in beta-lactam resistance pathway. B- and T-cell epitopes of the selected OMPs were predicted using BCPred as well as Propred I and Propred (http://crdd.osdd.net/raghava/propred/), respectively. Each of these OMPs contains regions which are capable to induce B- and T-cell immune responses. Conclusion Analysis acquired from this study showed that five selected OMPs have great potential for vaccine development against S. flexneri infection. The predicted immunogenic epitopes can also be used for development of peptide vaccines or multi-epitope vaccines against human shigellosis. Reverse vaccinology is a promising strategy for the discovery of potential vaccine candidates which can be used for future vaccine development against global persistent infections.
A mutation-independent CRISPR-Cas9–mediated gene targeting approach to treat a murine model of ornithine transcarbamylase deficiency

AAV- and CRISPR-Cas9–mediated gene targeting in neonatal mice led to clinical benefits in a mouse model of OTC deficiency. Ornithine transcarbamylase (OTC) deficiency is an X-linked urea cycle disorder associated with high mortality. Although a promising treatment for late-onset OTC deficiency, adeno-associated virus (AAV) neonatal gene therapy would only provide short-term therapeutic effects as the non-integrated genome gets lost during hepatocyte proliferation. CRISPR-Cas9-mediated homology-directed repair can correct a G-to-A mutation in 10% of OTC alleles in the livers of newborn OTC spfash mice. However, an editing vector able to correct one mutation would not be applicable for patients carrying different OTC mutations, plus expression would not be fast enough to treat a hyperammonemia crisis. Here, we describe a dual-AAV vector system that accomplishes rapid short-term expression from a non-integrated minigene and long-term expression from the site-specific integration of this minigene without any selective growth advantage for OTC-positive cells in newborns. This CRISPR-Cas9 gene-targeting approach may be applicable to all patients with OTC deficiency, irrespective of mutation and/or clinical state.
Dexmedetomidine Attenuates Monocyte-Endothelial Adherence via Inhibiting Connexin43 on Vascular Endothelial Cells

Current studies have identified the multifaceted protective functions of dexmedetomidine on multiple organs. For the first time, we clarify effects of dexmedetomidine on monocyte-endothelial adherence and whether its underlying mechanism is relative to connexin43 (Cx43), a key factor regulating monocyte-endothelial adherence. U937 monocytes and human umbilical vein endothelial cells (HUVECs) were used to explore monocyte-endothelial adherence. Two special siRNAs were designed to knock down Cx43 expression on HUVECs. U937-HUVEC adhesion, adhesion-related molecules, and the activation of the MAPK (p-ERK1/2, p-p38, and p-JNK1/2) signaling pathway were detected. Dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), was given as pretreatments to HUVECs. Its effects on Cx43 and U937-HUVEC adhesion were also investigated. The results show that inhibiting Cx43 on HUVECs could attenuate the contents of MCP-1, soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1), and the nonprocessed variants of the adhesion molecules ICAM-1 and VCAM-1 and ultimately result in U937-HUVEC adhesion decrease. Meanwhile, the activation of MAPKs was also inhibited. U0126 (inhibiting p-ERK1/2) and SB202190 (inhibiting p38) decreased the contents of MCP-1, sICAM-1, and sVCAM-1, but SP600125 (inhibiting p-JNK1/2) had none of these effects. ICAM-1 and VCAM-1 could be regulated in a similar way. Dexmedetomidine pretreatment inhibited Cx43 on HUVECs, the activation of MAPKs, and U937-HUVEC adhesion. Therefore, we conclude that dexmedetomidine attenuates U937-HUVEC adhesion via inhibiting Cx43 on HUVECs modulating the activation of MAPK signaling pathways.
Prognostic Value of Serum Osteopontin in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Background Acute exacerbation (AE) is a common cause of rapid deterioration and high mortality in idiopathic pulmonary fibrosis (IPF) patients. Osteopontin (OPN) plays an important role in IPF, but the studies about serum OPN in AE-IPF are unclear. We aimed to investigate whether OPN had a potential prognostic value in acute exacerbation and mortality in IPF. Methods Thirty-two patients with AE-IPF, 39 with S-IPF, and 20 healthy controls were included. Serum OPN and KL-6 levels were compared between AE-IPF and S-IPF. Logistic regression analysis was applied to identify the predicted value of OPN for AE. Kaplan–Meier curves were used to display survival, and Cox proportional hazards regression was used to identify risk for mortality. Results In AE-IPF patients, serum OPN levels were significantly higher than in S-IPF subjects (p < 0.001) or healthy controls (p < 0.001) or healthy controls (p < 0.001) or healthy controls (p < 0.001) or healthy controls (p < 0.001) or healthy controls (p < 0.001) or healthy controls (p < 0.001) or healthy controls (p < 0.001) or healthy controls (p < 0.001) or healthy controls (p < 0.001) or healthy controls ( Conclusion Elevated OPN could be a potential serum predictor for AE status and survival in IPF patients.
Get a grip—evolution of claw shape in relation to microhabitat use in intertidal arthropods (Acari, Oribatida)

Claws may be the most common biological attachment devices in animals but relatively few studies have examined the ecological and evolutionary significance of their morphology. We performed the first geometric morphometric investigation of arthropod claws using 15 intertidal oribatid mite species from two different families living in three different habitat types to determine if claw shape is correlated with ecology. Our results show that species living on rocky shores show remarkably high and strongly curved claws while species from mangrove habitats show significantly lower and less curved claws. Euryoecious species are able to dwell in a wide range of habitats and show an intermediate claw type. These results indicate a strong relationship between claw shape and microhabitat and the best predictors of microhabitat use seem to be claw height and curvature. Claw length varied to some degree among the species but without any noticeable ecological pattern. A comparison with terrestrial and freshwater aquatic oribatid mite species, on the other hand, confirms that their claws are only half as long as that of intertidal mites and it is suggested that tidal flooding and wave action strongly selects for long claws. In this microarthropod group which occupies a vast array of microhabitats, claw morphology may play an important role in niche separation and hence demonstrate the importance of ecomorphological studies.
Conceptualization of Heterogeneity of Chronic Diseases and Atherosclerosis as a Pathway to Precision Medicine: Endophenotype, Endotype, and Residual Cardiovascular Risk

The article discusses modern approaches to the conceptualization of pathogenetic heterogeneity in various branches of medical science. The concepts of endophenotype, endotype, and residual cardiovascular risk and the scope of their application in internal medicine and cardiology are considered. Based on the latest results of studies of the genetic architecture of atherosclerosis, five endotypes of atherosclerosis have been proposed. Each of the presented endotypes represents one or another pathophysiological mechanism of atherogenesis, having an established genetic substrate, a characteristic panel of biomarkers, and a number of clinical features. Clinical implications and perspectives for the study of endotypes of atherosclerosis are briefly reviewed.
Forced oscillation technique as a predictor for loss of control in asthmatic children

Background A reliable objective tool using as a predictor of asthma control status could assist asthma management. Objective To find the parameters of forced oscillation technique (FOT) as predictors for the future loss of asthma symptom control. Methods Children with well-controlled asthma symptom, aged 6–12 years, were recruited for a 12-week prospective study. FOT and spirometer measures and their bronchodilator response were evaluated at baseline. The level of asthma symptom control was evaluated according to Global Initiative for Asthma. Results Among 68 recruited children, 41 children (60.3%) maintain their asthma control between 2 visits (group C-C), and 27 children (39.7%) lost their asthma control on the follow-up visit (group C-LC). Baseline FOT parameters, including the values of respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), respiratory reactance at 5 Hz, area of reactance, %predicted of R5 and percentage of bronchodilator response (%∆) of R5 and R20 were significantly different between C-C and C-LC groups. In contrast, only %∆ of forced vital capacity, forced expiratory volume in 1 second (FEV1), and FEF25%–75% (forced expiratory flow 25%–75%) were significantly different between groups. Multiple logistic regression analysis revealed that %predicted of R5, %∆R5, %predicted of FEV1 and %∆FEV1 were the predictive factors for predicting the future loss of asthma control. The following cutoff values demonstrated the best sensitivity and specificity for predicting loss of asthma control: %predicted of R5=91.28, %∆R5=21.2, %predicted of FEV1=89.5, and %∆FEV1=7.8. The combination of these parameters predicted the risk of loss of asthma control with area under the curve of 0.924, accuracy of 83.8%. Conclusion Resistance FOT measures have an additive role to spirometric parameter in predicting future loss of asthma control.
MicroRNA 885-5p Inhibits Hepatocellular Carcinoma Metastasis by Repressing AEG1

Background Hepatocellular carcinoma (HCC) is the third major cause of cancer-related death. Mounting evidence shows that microRNAs play critical roles in the initiation and progression of HCC and may potentially serve as diagnostic markers for HCC. Methods and Results In the present study, we explored the biological effects of miR-885-5p on HCC progression. We performed flow cytometry analyses of miR-885-5p in HCC cell lines and identified miR-885-5p as a recurrence-related microRNA. Overexpression of miR-885-5p significantly inhibited cell migration, invasion, proliferation, angiogenesis and EMT. Then, the correlation of miR-885-5p and AEG1 were confirmed by using luciferase assays, quantitative real-time PCR analysis and Western blotting. It was subsequently confirmed that Astrocyte Elevated Gene1 (AEG1) was a direct target gene of miR-885-5p. Conclusion miR-885-5p likely acts as a tumor suppressor by regulating AEG1, suggesting that miR-885-5p may be a potential biomarker and can be targeted in therapeutic strategies against HCC in the future.
Histoplasma capsulatum Infection in an Allogeneic Hematopoietic Stem Cell Transplant Patient Receiving Voriconazole Prophylaxis

Histoplasma capsulatum infection is a rare complication in the allogeneic stem cell transplant patients. Minimal guidance exists on how to appropriately manage histoplasmosis in these patients. We report a patient who developed Histoplasma pneumonia while receiving voriconazole prophylaxis at a therapeutic trough level. The patient experienced significant clinical improvement after initiation of itraconazole pharmacotherapy. We recommend a lower threshold for evaluation for histoplasmosis in allogeneic hematopoietic stem cell transplant recipients who live in endemic regions, regardless of their antifungal prophylactic regimen.
On the longitudinal vibration of the railway bogie

This paper examines the influence of the rebound longitudinal motion of the bogie upon the vibration behaviour in the bogie. The analysis is based on the results of the numerical simulations developed on the basis of a general model with a nine-degree freedom of the bogie-track system, which takes into account the rigid vibration modes of the bogie – bounce, pitch and rebound, vertical and longitudinal displacements of the wheels, vertical displacements of the rails, and the wheel-rail contact elasticity, and a simplified model that does not consider the bogie longitudinal vibrations of rebound. The bogie vibration behaviour is assessed based on the power spectral density of the vertical acceleration and root mean square of vertical acceleration. It is highlighted the increase of the vibration level of the bogie due to the coupling effect between the pitch and rebound longitudinal vibrations, which, however, does not exceed 3-4% in terms of acceleration.
The Study of the Influence of Ultrasonic Vibrations on Structural Changes of Steel

The paper describes a cause of the geometric accuracy degradation of slender metallic products during their operation, which consists in the relaxation of residual stresses accumulated while product manufacturing. The most promising technology among the existing technologies of residual stress relaxation is based on the use of vibromechanical vibrations. This technology has high performance and low energy consumption. The reason for the relaxation of residual stresses under the action of vibromechanical vibrations is the gradual accumulation of internal energy, which leads to plastic dislocation shifts upon reaching a critical level. The dislocation motion under the action of vibromechanical vibrations continues until the dislocations take a more compact layout that corresponds to the equilibrium energy state. For technological implementation of the process there was developed a method of ultrasonic stabilization of elastic plates, which serve as sensing elements in differential-pressure transducers. The experimental studies of ultrasonic stabilization are carried out. According to the results of the studies, there have been conducted tests of the microstructure of the control samples. It is established that the samples of steel 20CH13 subject to ultrasonic treatment have a more uniform structure than the samples after the factory technology of long "aging". This confirms the assumption about the structural-energy processes occurring during vibromechanical relaxation of residual stresses. The technology of ultrasonic stabilization can be recommended as a replacement to the "aging" technology on the basis of the obtained results.
Effect of Disperse Reinforcement on the Structural Quality Factor of Vibrated and Centrifuged Concretes on the Сombined Aggregate

The article considers and evaluates the impact of dispersed reinforcement of vibrated and centrifuged concretes manufactured with various types of fibers on their strength-density ratio. The authors considered the application of such a recipe manufacturing method as combining aggregates by the example of heavyweight aggregate - crushed stone and light aggregate - expanded clay aggregate for these concretes. Registered strength-density ratio of centrifuged fibrous concretes with a combined aggregate is higher than vibrated concretes with the same composition of the studied fibers. The highest growth of the strength-density ratio for the centrifuged fibrous concretes as compared with the vibrated ones was identified in case of dispersed reinforcement with steel fiber.
Reinforcement Learning 101 with a Virtual Reality Game

Our proof-of-concept demonstrates how Virtual Reality can be used to explain the basic concepts of Reinforcement Learning. This application visualizes the learning process of Watkins’ Q( λ ), a fundamental algorithm in the ﬁeld, in the form of an interactive treasure hunt game. A player takes the role of an autonomous agent, and must learn the shortest path to a hidden treasure through experience. The application also allows an audience to follow the game from an external display.
Hindered Transport of Bacteria in Porous Media Flows

Swimming bacteria play crucial roles in processes ranging from the biodegradation of pollutants in groundwater to the spread of infections in the human body. The environments inhabited by these motile cells are characterized by porous microstructure and dynamic fluid flows. We show that the complex interplay between motility, geometry, and flow can lead to heterogeneous distributions of bacteria and severely hindered bacterial transport properties. Using video microscopy, we track the motion of bacteria (Bacillus subtilis) flowing through a microfluidic porous medium and complement these measurements by Langevin simulations. Cell trajectories reveal filamentous patterns of high cell concentration that result from the orientational coupling of cell elongation to the flow (Jeffery orbits) and steric surface interactions. The effective diffusion coefficient of the bacteria is severely hindered in the transverse flow direction with increasing mean shear rate due to the faster decorrelation of the cells’ orientation by shear.
A Comparison of Rendering Techniques for 3D Line Sets With Transparency

This article presents a comprehensive study of rendering techniques for 3D line sets with transparency. The rendering of transparent lines is widely used for visualizing trajectories of tracer particles in flow fields. Transparency is then used to fade out lines deemed unimportant, based on, for instance, geometric properties or attributes defined along with them. Accurate blending of transparent lines requires rendering the lines in back-to-front or front-to-back order, yet enforcing this order for space-filling 3D line sets with extremely high-depth complexity becomes challenging. In this article, we study CPU and GPU rendering techniques for transparent 3D line sets. We compare accurate and approximate techniques using optimized implementations and several benchmark data sets. We discuss the effects of data size and transparency on quality, performance, and memory consumption. Based on our study, we propose two improvements to per-pixel fragment lists and multi-layer alpha blending. The first improves the rendering speed via an improved GPU sorting operation, and the second improves rendering quality via transparency-based bucketing.
Light-Mediated Shape Transformation of Self-rolling Nanocomposite Hydrogel Tube.

Self-rolling of a planar hydrogel sheet represents an advanced approach to fabricate tubular construct which is of significant interest in biomedicine. However, the self-rolling tube is usually lacking in remote controllability and requires a relatively tedious fabrication procedure. Herein, we present an easy and controllable approach to fabricate self-rolling tubes which can respond to both magnetic field and light. With the introduction of magnetic nanorods in a hydrogel precursor, a strain gradient is created across the thickness of the formed hydrogel sheet during the photopolymerization process. After removal of the strain constraint, the nanocomposite sheet rolls up spontaneously. The self-rolling scenario of the sheet can be tuned by varying the sheet geometry and the magnetic nanorod concentration in the hydrogel precursor. The nanocomposite hydrogel tube translates in the presence of a magnetic field and produces heat upon a near-infrared (NIR) light illumination by virtue of the magnetic and photo-thermal properties of the magnetic nanorods. The self-rolling tube either opens up or expands its diameter under NIR light irradiation depending on the number of rolls in the tube. With the use of a thermo-responsive hydrogel material, we demonstrate the magnetically-guided motion of the chemical-bearing nanocomposite hydrogel tube and its controlled chemical release through its light-mediated deformation. The approach reported herein is expected to be applicable to other self-rolling polymer-based dry materials and the nanocomposite hydrogel tube presented in this work may find potential applications in soft robot and controlled release of drug.
Degradation Potential of the Nonylphenol Monooxygenase of Sphingomonas sp. NP5 for Bisphenols and Their Structural Analogs

The nonylphenol-degrading bacterium Sphingomonas sp. strain NP5 has a very unique monooxygenase that can attack a wide range of 4-alkylphenols with a branched side chain. Due to the structural similarity, it can also attack bisphenolic compounds, which are very important materials for the synthesis of plastics and resins, but many of them are known to or suspected to have endocrine disrupting effects to fish and animals. In this study, to clarify the substrate specificity of the enzyme (NmoA) for bisphenolic compounds, degradation tests using the cell suspension of Pseudomonas putida harboring the nonylphenol monooxygenase gene (nmoA) were conducted. The cell suspension degraded several bisphenols including bisphenol F, bisphenol S, 4,4′-dihydroxybenzophenone, 4,4′-dihydroxydiphenylether, and 4,4′-thiodiphenol, indicating that this monooxygenase has a broad substrate specificity for compounds with a bisphenolic structure.