bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision-Cut Bovine Udder Slices (PCBUS) as an in-vitro-model of an early phase of infection of bovine mastitis
Authors: Filor Viviane , Petry Monique , Meißner Jessica , Kietzmann Manfred 
Published: November 2020

Abstract
Background: The aim of this study was the establishment of precision-cut bovine udder slices (PCBUS) as an in-vitro -model to investigate pathophysiological processes in the early phase of mastitis in order to have the possibility to investigate new therapeutic approaches for the treatment of such udder inflammation in later studies. Furthermore, this model should contribute to substitute in-vivo -experiments. Bovine mastitis is one of the most common and costly infectious diseases in the dairy industry, which is largely associated with the use of antimicrobial agents. Given this problem of antimicrobial resistance, it is essential to step up research into bacterial infectious diseases. Thus, the transfer of the in-vitro -model of precision-cut tissue slices to the bovine udder enables broad research into new therapeutic approaches in this area and can also be used to address issues in basic research or the characterization of complex pathophysiological processes. Results: A stimulation with LPS, PGN or the combination of both substances (LPS:PGN) demonstrated the ability of the PCBUS to react with a significant secretion of IL-1ß, TNF-α and PGE 2 . Conclusion: The slices represent an instrument for investigating pharmacological interactions with udder tissue, which can be useful for studies on pharmacological questions and the understanding of complex pathophysiological processes of infection and inflammation.
Parasitism of Aedes albopictus by Ascogregarina taiwanensis lowers its competitive ability against Aedes triseriatus.
Authors: Stump Emma , Childs Lauren M , Walker Melody 
Published: November 2020

Abstract
Background: Mosquitoes are vectors for diseases that significantly impact the human population such as dengue, malaria and La Crosse virus. When multiple mosquito species are present, the competition between species may alter population dynamics as well as disease spread. Two mosquito species, Aedes albopictus and Aedes triseriatus, both inhabit areas where La Crosse virus is found. Infection of Aedes albopictus by the parasite Ascogregarina taiwanensis and Aedes triseriatus by the parasite Ascogregarina barretti can decrease a mosquito’s fitness, respectively. In particular, the decrease in fitness of Aedes albopictus occurs through the impact of Ascogregarina taiwanensis on female fecundity, larval development rate, and larval mortality and may impact its initial competitive advantage over Aedes triseriatus during invasion.Methods: We examine the effects of parasitism of gregarine parasites on Aedes albopictus and triseriatus population dynamics and competition with a focus on when Aedes albopictus is new to an area. We build a compartmental model including competition between Aedes albopictus and triseriatus while under parasitism of the gregarine parasites. Using parameters based on literature, we simulate the dynamics and analyze the equilibrium population proportion of the two species. We consider the presence of both parasites and potential dilution effects.Results: We show that increased levels of parasitism in Aedes albopictus will decrease the initial competitive advantage of the species over Aedes triseriatus and increase the survivorship of Aedes triseriatus. We find Aedes albopictus is better able to invade when there is more extreme parasitism of Aedes triseriatus. Furthermore, although the transient dynamics differ, dilution of the parasite density through uptake by both species does not alter the equilibrium population sizes of either species.Conclusions: Mosquito population dynamics are affected by many factors, such as abiotic factors (e.g. temperature and humidity) and competition between mosquito species. This is especially true when multiple mosquito species are vying to live in the same area. Knowledge of how population dynamics are affected by gregarine parasites among competing species can inform future mosquito control efforts and help prevent the spread of vector-borne disease.
Comparison of deep learning with regression analysis in creating predictive models for SARS-CoV-2 outcomes
Authors: Abdulaal Ahmed , Patel Aatish , Charani Esmita , Denny Sarah , Alqahtani Saleh A , Davies Gary W , Mughal Nabeela , Moore Luke SP 
Published: November 2020

Abstract
Background Accurately predicting patient outcomes in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could aid patient management and allocation of healthcare resources. There are a variety of methods which can be used to develop prognostic models, ranging from logistic regression and survival analysis to more complex machine learning algorithms and deep learning. Despite several models having been created for SARS-CoV-2, most of these have been found to be highly susceptible to bias. We aimed to develop and compare two separate predictive models for death during admission with SARS-CoV-2.MethodBetween March 1 - April 24, 2020, 398 patients were identified with laboratory confirmed SARS-CoV-2 in a London teaching hospital. Data from electronic health records were extracted and used to create two predictive models using: 1) a Cox regression model and 2) an artificial neural network (ANN). Model performance profiles were assessed by validation, discrimination, and calibration.Results Both the Cox regression and ANN models achieved high accuracy (83.8%, 95% confidence interval (CI): 73.8 - 91.1 and 90.0%, 95% CI: 81.2 - 95.6, respectively). The area under the receiver operator curve (AUROC) for the ANN (92.6%, 95% CI: 91.1 - 94.1) was significantly greater than that of the Cox regression model (86.9%, 95% CI: 85.7 - 88.2), p=0.0136. Both models achieved acceptable calibration with Brier scores of 0.13 and 0.11 for the Cox model and ANN, respectively. ConclusionWe demonstrate an ANN which is non-inferior to a Cox regression model but with potential for further development such that it can learn as new data becomes available. Deep learning techniques are particularly suited to complex datasets with non-linear solutions, which make them appropriate for use in conditions with a paucity of prior knowledge. Accurate prognostic models for SARS-CoV-2 can provide benefits at the patient, departmental and organisational level.
Survey study of research integrity officer perceptions of research practices associated with instances of research misconduct
Authors: Kalichman Michael 
Published: November 2020

Abstract
Background: Research on research integrity has tended to focus on frequency of research misconduct and factors that might induce someone to commit research misconduct. A definitive answer to the first question has been elusive, but it remains clear that any research misconduct is too much. Answers to the second question are so diverse, it might be productive to ask a different question: What about how research is done allows research misconduct to occur? Methods: With that question in mind, research integrity officers (RIOs) of the 62 members of the American Association of Universities were invited to complete a brief survey about their most recent instance of a finding of research misconduct. Respondents were asked whether one or more good practices of research (e.g., openness and transparency, keeping good research records) were present in their case of research misconduct. Results: Twenty-four (24) of the respondents (39% response rate) indicated they had dealt with at least one finding of research misconduct and answered the survey questions. Over half of these RIOs reported that their case of research misconduct had occurred in an environment in which at least nine of the ten listed good practices of research were deficient. Conclusions: These results are not evidence for a causal effect of poor practices, but it is arguable that committing research misconduct would be more difficult if not impossible in research environments adhering to good practices of research.
Identification and biochemical characterisation of Acanthamoeba castellanii cysteine protease 3
Authors: Wang Zhixin , Wu Duo , Tachibana Hiroshi , Feng Meng , Cheng Xunjia 
Published: November 2020

Abstract
Background: Acanthamoeba spp. are free-living amoeba that are ubiquitously distributed in the environment. This study examines pathogenic Acanthamoeba cysteine proteases (AcCPs) belonging to the cathepsin L-family and explores the mechanism of AcCP3 interaction with host cells.Methods: Six AcCP genes were amplified by polymerase chain reaction (PCR). Quantitative real-time PCR was used to analyse the relative mRNA expression of AcCPs during the encystation process, and between pre- and post-reactivated trophozoites. To further verify the role of AcCP3 in these processes, AcCP3 recombinant proteins were expressed in Escherichia coli, and the hydrolytic activity of AcCP3 was determined. The influence of the AcCP3 on the hydrolytic activity of trophozoites and the toxicity of trophozoites to human corneal epithelial cells (HCECs) was examined by inhibiting AcCP3 expression using siRNA. Further, the levels of p-Raf and p-Erk were examined in HCECs following coculture with AcCP3 gene knockdown trophozoites by western blotting.Results: During encystation, five out of six AcCPs exhibited decreased expression, and only AcCP6 was substantially up-regulated at the mRNA level, indicating that most AcCPs were not directly correlated to encystation. Further, six AcCPs exhibited increased expression level following trophozoite reactivation with HEp-2 cells, particularly AcCP3, indicating that these AcCPs might be virulent factors. After refolding of recombinant AcCP3 protein, the 27 kDa mature protein from the 34 kDa pro-protein hydrolysed host haemoglobin, collagen and albumin, and showed high activity in an acidic environment. After AcCP3 knockdown, the hydrolytic activity of trophozoite crude protein against gelatin was decreased, suggesting that these trophozoite had decreased toxicity. Compared with untreated trophozoites or negative control siRNA-treated trophozoites, AcCP3-knockdown trophozoites were less able to penetrate and damage monolayers of HCECs. Western blot analysis showed that the activation levels of the Ras/Raf/Erk/p53 signalling pathways in HCECs decreased after inhibiting the expression of trophozoite AcCP3.Conclusions: AcCP6 was correlated to encystation. Further, AcCP3 was a virulent factor in trophozoites, and participated in the activation of the Ras/Raf/Erk/p53 signalling pathways of host cells.
Identification of an IRF10 gene in common carp (Cyprinus carpio L.) and analysis of its function in the antiviral and antibacterial immune response
Authors: Zhu Yaoyao , Shan Shijuan , Zhao Huaping , Liu Rongrong , Wang Hui , Chen Xinping , Yang Guiwen , Li Hua 
Published: November 2020

Abstract
Background: Interferon (IFN) regulatory factors (IRFs), as transcriptional regulatory factors, play important roles in regulating the expression of type I IFN and IFN stimulated genes (ISGs) in innate immune responses. In addition, they participate in cell growth and development and regulate oncogenesis. Results: In the present study, the cDNA sequence of IRF10 in common carp (Cyprinus carpio L.) was characterized (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52.7-89.2% identity with other teleost IRF10s and contained a DNA-binding domain (DBD), a nuclear localization signal (NLS) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF10 had the closest relationship with IRF10 of Ctenopharyngodon idella. CcIRF10 transcripts were detectable in all examined tissues, with the highest expression in the gonad and the lowest expression in the head kidney. CcIRF10 expression was upregulated in the spleen, head kidney, foregut and hindgut upon polyinosinic:polycytidylic acid (poly I:C) and Aeromonas hydrophila stimulation and induced by poly I:C, lipopolysaccharide (LPS) and peptidoglycan (PGN) in peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs) of C. carpio. In addition, overexpression of CcIRF10 was able to decrease the expression of the IFN and IFN stimulated genes PKR and ISG15. Conclusions: These results indicate that CcIRF10 participates in antiviral and antibacterial immunity and negatively regulates the IFN response, which provides new insights into the IFN system of C. carpio.
Injury Mechanism Affects the Stability of Suture-Button Syndesmosis Fixation.
Authors: Chen Kuan Hao , Chen Chih Hwa , Huang Yu Min , Lee Hsieh Hsing , Tsuang Yang Hwei 
Published: November 2020

Abstract
Background: Ankle syndesmosis injury is a common condition, and the injury mechanism can be sorted into pure-syndesmosis injury, Weber-B and Weber-C type fractures. This study aims to evaluate the treatment outcomes and stability of suture-button fixation for syndesmosis injury with different injury mechanisms. We hypothesized that injury mechanisms would alter the stability of suture-button fixation.Methods: We retrospectively reviewed 63 patients with ankle syndesmosis injury underwent surgery with TightRope (Arthrex, Naples, FL, USA) from April 2014 to February 2019. The stability of suture-button fixation with TightRope were evaluated by comparing the preoperative, postoperative, and final follow-up measurements of tibiofibular clear space (TFCS), tibiofibular overlap (TFO), and medial clear space (MCS). A subgroup analysis for each demographic group and injury type including pure-syndesmosis injury, Weber-B and Weber-C type fractures were performed.Results: Syndesmosis was effectively reduced using TightRope. After the index surgery, the tibiofibular clear space was reduced from 7.73 mm to 4.04 mm, the tibiofibular overlap was increased from 3.05 mm to 6.44 mm, and the medial clear space was reduced from 8.12 mm to 3.54 mm. However, syndesmosis widening was noted at the final follow-up, especially in Weber-C type fractures (TFCS: 3.82 to 4.45 mm, p < 0.01 and TFO: 6.86 to 6.29 mm, p = 0.04). Though widened, the final follow-up values of tibiofibular clear space and tibiofibular overlap were in the acceptable range. Postoperatively and at the final follow-up, medial clear space was found to be significantly larger in the Weber-C group than in the pure syndesmosis and Weber-B groups (p < 0.05). Conclusions: Suture-button fixation can offer anatomic reduction and dynamic fixation in syndesmosis injuries. However, when using this modality for Weber-C type fractures, more attention should be focused on the accuracy of reduction, especially of medial clear space, and rediastasis should be carefully monitored.Trial registration: This trial was retrospectively approved by TMU-JIRB. Registration number N202004122, and the date of approval was May 06, 2020.
Analysis of the Spatial Distribution of Aedes Albopictus by Indicator Kriging in an Urban Area of Shanghai, China
Authors: Zhou Yibin , Liu Hongxia , Leng Peien , Zhu Jiang , Yao Shenjun , Zhu Yiyi , Wu Huanyu 
Published: November 2020

Abstract
Background: Aedes albopictus is a well-recognized vector of major arboviral diseases and a primary pest in tropical and temperate regions of China. In the current monitoring system for the spread of Ae. albopictus based on the sub-district scale in most cities of China, spatial distribution has not been considered for the analysis of the density of species. So, the system is not accurate enough for epidemic investigations, especially in big cities like Shanghai.Methods: In this study, an improved surveillance program integrating the actual monitoring locations was used to investigate the temporal and spatial distribution of Ae. albopictus abundance in an urban area of Shanghai, China, from 2018 to 2019 by using the mosquito-oviposition trap (MOT) method. The study area of 14 sub-districts was divided into 133 grids. The vector abundance and spatial structure of Ae. Albopictus were predicted by the indicator Kriging based on eight MOTs in each grid. Meanwhile, the light trap (LT) method was also used for the analysis and compared with the MOT method.Results: A total of 8,192 MOTs were placed in the study area in 2018, and 7,917 (96.6%) were retrieved with a positive rate of 6.45%, while in 2019, 22,715 (97.0%) of 23,408 MOTs were recovered with a positive rate of 5.44%. When using the LT method, 273 (93.5%) and 312 (94.5%) adult female Ae. albopictus were gathered in 2018 and 2019, respectively. The Ae. albopictus populations in the urban area of Shanghai increased slowly from May, reached a peak in July, and declined gradually from September. The MOT positivity index (MPI) showed a significant positive spatial autocorrelation across the study area, while LT collections indicated a non-significant spatial autocorrelation. The MPI was suitable for spatial interpolation by using the indicator Kriging and showed different hotspots in different years.Conclusions: The improved surveillance system integrating geographic information can help improve our understanding of the spatial and temporal distribution of Ae. albopictus in urban areas of Shanghai and could provide a practical method for decision-makers to implement vector control and management of mosquitoes.
Model uncertainty and decision making: Predicting the Impact of COVID-19 Using the CovidSim Epidemiological Code
Authors: Edeling Wouter , Hamid Arabnejad , Sinclair Robert , Suleimenova Diana , Gopalakrishnan Krishnakumar , Bosak Bartosz , Groen Derek , Mahmood Imran , Crommelin Daan , Coveney Peter 
Published: November 2020

Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus has rapidly spread worldwide since December 2019, and early modelling work of this pandemic has assisted in identifying effective government interventions. The UK government relied in part on the CovidSim model developed by the MRC Centre for Global Infectious Disease Analysis at Imperial College London, to model various non-pharmaceutical intervention strategies, and guide its government policy in seeking to deal with the rapid spread of the COVID-19 pandemic during March and April 2020. CovidSim is subject to different sources of uncertainty, namely parametric uncertainty in the inputs, model structure uncertainty (i.e., missing epidemiological processes) and scenario uncertainty, which relates to uncertainty in the set of conditions under which the model is applied. We have undertaken an extensive parametric sensitivity analysis and uncertainty quantification of the current CovidSim code. From the over 900 parameters that are provided as input to CovidSim, we identified a key subset of 19 parameters to which the code output is most sensitive. We find that the uncertainty in the code is substantial, in the sense that imperfect knowledge in these inputs will be magnified to the outputs, up to the extent of ca. 300%. Most of this uncertainty can be traced back to the sensitivity of three parameters. Compounding this, the model can display significant bias with respect to observed data, such that the output variance does not capture this validation data with high probability. We conclude that quantifying the parametric input uncertainty is not sufficient, and that the effect of model structure and scenario uncertainty cannot be ignored when validating the model in a probabilistic sense.
Functionalized osteoarthritis targeting peptides for MRI, lubricant and regenerative medicine
Authors: Lin Chin-Yu , Wang Yung-Li , Chi Yi-Hsuan , Chan Long Yi , Chen Kuan-Wen , Hsu Horng-Chaung , Hwang Dennis W , Wu Han-Chung , Hung Shih-Chieh 
Published: November 2020

Abstract
Despite the efforts made for osteoarthritis (OA) treatment, the results are limited and can be improved by enhancing the OA homing strategy. Here, we used a phage display system to identify OA-targeting peptides, and combined them with magnetic resonance imaging detection reagents to expand their application to early OA diagnosis in rat and swine models. OA-targeting peptides showed better static and kinetic friction characteristics than scrambled peptides, when conjugated with hyaluronic acid for rheological lubrication studies using human OA specimens. Furthermore, mesenchymal stem cells, through CD44 binding to hyaluronic acid conjugated with OA-targeting peptides, showed better capacity for OA homing and repair than those conjugated with scrambled peptides. Protein–peptide docking revealed WXPXW as the consensus binding motifs that bind to collagen XII, a protein exclusively expressed in human and animal OA models. These results suggest the potential of OA-targeting peptides to promote diagnosis, treatment, and regenerative medicine for OA.
Prehospital Prediction of a Time-sensitive Condition Among Patients With Dizziness Assessed by the Emergency Medical Service&nbsp;
Authors: Magnusson Carl , Gärskog Julia , Lökholm Elin , Stenström Jonny , Wetter Rickard , Axelsson Christer , Hagiwara Magnus Andersson , Packendorff Niclas , Jood Katarina , Karlsson Thomas , Herlitz Johan 
Published: November 2020

Abstract
Background: Dizziness is a relatively common symptom among patients who call for the emergency medical service (EMS).Methods: All patients assessed by the EMS and triaged using the rapid emergency triage and treatment system for adults code 11 (=dizziness) in the 660,000 inhabitants in the Municipality of Gothenburg, Sweden, in 2016, were considered for inclusion. The patients were divided into two groups according to the final diagnosis (a time-sensitive condition, yes or no).Results: There were 1,536 patients who fulfilled the inclusion criteria, of which 96 (6.2%) had a time-sensitive condition. The majority of these had an acute cerebrovascular disease. Eight predictors of a time-sensitive condition were identified. Three were associated with a reduced risk: 1) the dizziness was of a rotatory type, 2) the dizziness had a sudden onset and 3) increasing body temperature. Five were associated with an increased risk: 1) sudden onset of headache, 2) a history of head trauma, 3) symptoms of nausea or vomiting, 4) on treatment with anticoagulants and 5) increasing systolic blood pressure.Conclusion: Among 1,536 patients who were assessed by the EMS due to dizziness, 6.2% had a time-sensitive condition. On the arrival of the EMS, eight factors were associated with the risk of having a time-sensitive condition. They were linked to the type of symptoms, to clinical findings on the arrival of the EMS and to the recent clinical history.