bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited available evidence supports theoretical predictions of reduced vaccine efficacy at higher exposure dose
Authors: Langwig Kate E. , Gomes M. Gabriela M. , Clark Mercedes D. , Kwitny Molly , Yamada Steffany , Wargo Andrew R. , Lipsitch Marc 
Published: March 2019

AbstractUnderstanding the causes of vaccine failure is important for predicting disease dynamics in vaccinated populations and planning disease interventions. Pathogen exposure dose and heterogeneity in host susceptibility have both been implicated as important factors that may reduce overall vaccine efficacy and cause vaccine failure. Here, we explore the effect of pathogen dose and heterogeneity in host susceptibility in reducing efficacy of vaccines. Using simulation-based methods, we find that increases in pathogen exposure dose decrease vaccine efficacy, but this effect is modified by heterogeneity in host susceptibility. In populations where the mode of vaccine action is highly polarized, vaccine efficacy decreases more slowly with exposure dose than in populations with less variable protection. We compared these theoretical results to empirical estimates from a systematic literature review of vaccines tested over multiple exposure doses. We found that few studies (nine of 5,389) tested vaccine protection against infection over multiple pathogen challenge doses, with seven studies demonstrating a decrease in vaccine efficacy with increasing exposure dose. Our research demonstrates that pathogen dose has potential to be an important determinant of vaccine failure, although the limited empirical data highlight a need for additional studies to test theoretical predictions on the plausibility of reduced host susceptibility and high pathogen dose as mechanisms responsible for reduced vaccine efficacy in high transmission settings.
The Grande Rose of the Reims Cathedral: an eight-century perspective on the colour management of medieval stained glass
Authors: Capobianco Natan , Hunault Myrtille O. J. Y. , Balcon-Berry Sylvie , Galoisy Laurence , Sandron Dany , Calas Georges 
Published: March 2019

AbstractThe Grande Rose of Reims Cathedral (France), a UNESCO Cultural Heritage Monument from the 13th century, underwent several restoration works during the 20th century. Its colours result from centuries of colour management from which little information remain. We used non-destructive and portable optical absorption spectroscopy to quantify glass colour and determine the colouring species on a large-scale study of this monumental window. We found six distinct colour groups, each containing both medieval and modern glasses, with colouring processes specific to each colour. This illustrates medieval glassmakers’ mastering of glass colouring and modern glassmakers’ management to reproduce medieval glasses colours. Full UV-visible-NIR energy range is necessary for determining the contribution of colouring elements as Fe2+ and Cu2+. Systematic thickness measurements reveal an average glass thickness of 3 mm and demonstrate the major control of chromophore concentration on glass colour. Yellow, red and purple colours arise from a single chromophore each, suggesting the use of well-defined glassmaking techniques leading to robust colour reproducibility. By contrast, blue and green glasses show different chromophore combinations depending on production time, which suggests more diversity in glassmaking techniques.
Early hospital readmissions after ABO- or HLA- incompatible living donor kidney transplantation
Authors: Lee Juhan , Kim Deok Gie , Kim Beom Seok , Kim Myoung Soo , Il Kim Soon , Kim Yu Seun , Huh Kyu Ha 
Published: March 2019

AbstractEarly hospital readmission (EHR) after kidney transplantation (KT) is associated with adverse outcomes and significant healthcare costs. Despite survival benefits, ABO- and HLA-incompatible (ABOi and HLAi) KTs require desensitization and potent immunosuppression that increase risk of EHR. However, little data exist regarding EHR after incompatible KT. We defined EHR as admission for any reason within 30 days of discharge from the index hospitalization. Patients who underwent living donor KT from 2010–2017 were classified into one of three groups (control, ABOi KT, or HLAi KT). Our study included 732 patients, 96 (13.1%) of who experienced EHR. HLAi KT patients had a significantly higher incidence of EHR than other groups (26.6%; P < 0.001). In addition, HLAi KT (HR, 2.26; 95% CI, 1.35–3.77; P = 0.002) and advanced age (≥60 years) (HR, 1.93; 95% CI, 1.20–3.12; P = 0.007) were independent risk factors for EHR. Patients with EHR showed 1.5 times and 3 times greater risk of late hospital readmission and death-censored graft loss, respectively, and consistently exhibited inferior renal function compared to those without EHR, regardless of immunologic incompatibilities. We recommend that KT recipients experiencing EHR or its risk factors be managed with extreme care due to their increased susceptibility to adverse outcomes.
Predicting seasonal influenza epidemics using cross-hemisphere influenza surveillance data and local internet query data
Authors: Zhang Yuzhou , Yakob Laith , Bonsall Michael B. , Hu Wenbiao 
Published: March 2019

AbstractCan early warning systems be developed to predict influenza epidemics? Using Australian influenza surveillance and local internet search query data, this study investigated whether seasonal influenza epidemics in China, the US and the UK can be predicted using empirical time series analysis. Weekly national number of respiratory cases positive for influenza virus infection that were reported to the FluNet surveillance system in Australia, China, the US and the UK were obtained from World Health Organization FluNet surveillance between week 1, 2010, and week 9, 2018. We collected combined search query data for the US and the UK from Google Trends, and for China from Baidu Index. A multivariate seasonal autoregressive integrated moving average model was developed to track influenza epidemics using Australian influenza and local search data. Parameter estimates for this model were generally consistent with the observed values. The inclusion of search metrics improved the performance of the model with high correlation coefficients (China = 0.96, the US = 0.97, the UK = 0.96, p < 0.01) and low Maximum Absolute Percent Error (MAPE) values (China = 16.76, the US = 96.97, the UK = 125.42). This study demonstrates the feasibility of combining (Australia) influenza and local search query data to predict influenza epidemics a different (northern hemisphere) scales.
Dye-coupling between neonatal spinal motoneurons and interneurons revealed by prolonged back-filling of a ventral root with a low molecular weight tracer in the mouse
Authors: Blivis Dvir , Falgairolle Melanie , O’Donovan Michael J. 
Published: March 2019

AbstractWe investigated dye-coupling between motoneurons in the L6 segment of the neonatal mouse spinal cord that contains limb-innervating motoneurons and sexually dimorphic motor nuclei. Using an isolated spinal cord preparation, we back-filled the cut, L6 ventral root with the small molecule Neurobiotin, or the much larger dextran-conjugated fluorophores for 16–24 hours. Motoneurons and parasympathetic preganglionic neurons were filled with both markers, but dye-coupling was only seen with Neurobiotin fills. Following a neurobiotin fill, fluorescence was observed in contralateral motoneurons, in motoneurons innervating adjacent ventral roots, and in ChAT-negative, putative interneurons outside of the motoneuron pools in addition to the directly back-labeled L6 motoneurons. It is known that the gap junction protein connexin-36 is widely expressed in the sexually dimorphic motoneurons of the L6 segment, suggesting that the dye-coupling is mediated by gap junctions. The technique has revealed previously unknown connections of motoneurons in the neonatal mouse cord that are likely to play important roles in the development and function of spinal circuits.
TBA225, a fusion toxoid vaccine for protection and broad neutralization of staphylococcal superantigens
Authors: Venkatasubramaniam Arundhathi , Adhikari Rajan P. , Kort Thomas , Liao Grant C. , Conley Shawn , Abaandou Laura , Kailasan Shweta , Onodera Yoshikuni , Krishnan Subramaniam , Djagbare Didier M. , Holtsberg Frederick W. , Karauzum Hatice , Aman M. Javad 
Published: March 2019

AbstractSuperantigens (SAgs) play a major role in the pathogenesis of Staphylococcus aureus and are associated with several diseases, including food poisoning, bacterial arthritis, and toxic shock syndrome. Monoclonal antibodies to these SAgs, primarily TSST-1, SEB and SEA have been shown to provide protection in animal studies and to reduce clinical severity in bacteremic patients. Here we quantify the pre-existing antibodies against SAgs in many human plasma and IVIG samples and demonstrate that in a major portion of the population these antibody titers are suboptimal and IVIG therapy only incrementally elevates the anti-SAg titers. Our in vitro neutralization studies show that a combination of antibodies against SEA, SEB,and TSST-1 can provide broad neutralization of staphylococcal SAgs. We report a single fusion protein (TBA225) consisting of the toxoid versions of TSST-1, SEB and SEA and demonstrate its immunogenicity and protective efficacy in a mouse model of toxic shock. Antibodies raised against this fusion vaccine provide broad neutralization of purified SAgs and culture supernatants of multiple clinically relevant S. aureus strains. Our data strongly supports the use of this fusion protein as a component of an anti-virulence based multivalent toxoid vaccine against S. aureus disease.
Automated detection of koalas using low-level aerial surveillance and machine learning
Authors: Corcoran Evangeline , Denman Simon , Hanger Jon , Wilson Bree , Hamilton Grant 
Published: March 2019

AbstractEffective wildlife management relies on the accurate and precise detection of individual animals. These can be challenging data to collect for many cryptic species, particularly those that live in complex structural environments. This study introduces a new automated method for detection using published object detection algorithms to detect their heat signatures in RPAS-derived thermal imaging. As an initial case study we used this new approach to detect koalas (Phascolarctus cinereus), and validated the approach using ground surveys of tracked radio-collared koalas in Petrie, Queensland. The automated method yielded a higher probability of detection (68–100%), higher precision (43–71%), lower root mean square error (RMSE), and lower mean absolute error (MAE) than manual assessment of the RPAS-derived thermal imagery in a comparable amount of time. This new approach allows for more reliable, less invasive detection of koalas in their natural habitat. This new detection methodology has great potential to inform and improve management decisions for threatened species, and other difficult to survey species.
Highly Sensitive Active-Matrix Driven Self-Capacitive Fingerprint Sensor based on Oxide Thin Film Transistor
Authors: Jeon Guk-Jin , Lee Seung-Hwan , Lee Seung Hee , Shim Jun-Bo , Ra Jong-Hyun , Park Kyoung Woo , Yeom Hye-In , Nam Yunyong , Kwon Oh-Kyong , Park Sang-Hee Ko 
Published: March 2019

AbstractThe fingerprint recognition has been widely used for biometrics in mobile devices. Existing fingerprint sensors have already been commercialized in the field of mobile devices using primarily Si-based technologies. Recently, mutual-capacitive fingerprint sensors have been developed to lower production costs and expand the range of application using thin-film technologies. However, since the mutual-capacitive method detects the change of mutual capacitance, it has high ratio of parasitic capacitance to ridge-to-valley capacitance, resulting in low sensitivity, compared to the self-capacitive method. In order to demonstrate the self-capacitive fingerprint sensor, a switching device such as a transistor should be integrated in each pixel, which reduces a complexity of electrode configuration and sensing circuits. The oxide thin-film transistor (TFT) can be a good candidate as a switching device for the self-capacitive fingerprint sensor. In this work, we report a systematic approach for self-capacitive fingerprint sensor integrating Al-InSnZnO TFTs with field-effect mobility higher than 30 cm2/Vs, which enable isolation between pixels, by employing industry-friendly process methods. The fingerprint sensors are designed to reduce parasitic resistance and capacitance in terms of the entire system. The excellent uniformity and low leakage current (<10−12) of the oxide TFTs allow successful capture of a fingerprint image.
Epidemiological characteristics of nasopharyngeal Streptococcus pneumoniae strains among children with pneumonia in Chongqing, China
Authors: Yu Yi-Yi , Xie Xiao-Hong , Ren Luo , Deng Yu , Gao Yu , Zhang Yao , Li Hui , Luo Jian , Luo Zheng-Xiu , Liu En-Mei 
Published: March 2019

AbstractStreptococcus pneumoniae (pneumococcus) is the most common respiratory pathogen worldwide. Nasopharyngeal carriage with S. pneumoniae is the major source of lower respiratory tract infection and horizontal spread among children. Investigating nasopharyngeal S. pneumoniae is crucial for clinicians to control pneumococcus disease. Here, we retrospectively analyzed clinical information of 5,960 hospitalized children, focusing on pneumonia children less than five years with positive nasopharyngeal pneumococcal cultures. Nasopharyngeal aspirates (NPAs) were collected between June 2009 and December 2016, which were outside the pneumococcal conjugate vaccine(PCV) period. NPAs were subjected to common bacterial culture and antibiotic susceptibility tests, and serotypes were identified by both multiplex PCR and DNA sequencing. Results clearly revealed that clinical manifestations of the children whose NPAs were S. pneumoniae culture positive were serious, especially in those less than twelve months old. Fifteen different serotypes of nasopharyngeal S. pneumoniae were detected, the most common ones being 19F (35.2%), 6A/B (23.8%), 19A (11.4%), 15B/C (9.3%) and 23F (7.8%). Eight serotypes, accounting for 85.5% of the isolates, corresponded to the PCV13 serotypes. Approximately one-third of all S. pneumoniae strains were susceptible to penicillin. Overall, we consider nasopharyngeal S. pneumoniae culture is beneficial in assessing the situations of pneumonia children. Moreover, PCV13 could be useful in preventing pneumococcal disease in Chongqing, China.
Transportan 10 improves the pharmacokinetics and pharmacodynamics of vancomycin
Authors: Ruczyński Jarosław , Rusiecka Izabela , Turecka Katarzyna , Kozłowska Agnieszka , Alenowicz Magdalena , Gągało Iwona , Kawiak Anna , Rekowski Piotr , Waleron Krzysztof , Kocić Ivan 
Published: March 2019

AbstractIn the presented study, transportan 10 (TP10), an amphipathic cell penetrating peptide (CPP) with high translocation activity, was conjugated with vancomycin (Van), which is known for poor access to the intracellular bacteria and the brain. The antibacterial activity of the conjugates was tested on selected clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus sp. It turned out that all of them had superior antimicrobial activity in comparison to that of free Van, which became visible particularly against clinical MRSA strains. Furthermore, one of the conjugates was tested against MRSA - infected human cells. With respect to them, this compound showed high bactericidal activity. Next, the same conjugate was screened for its capacity to cross the blood brain barrier (BBB). Therefore, qualitative and quantitative analyses of the conjugate’s presence in the mouse brain slices were carried out after its iv administration. They indicated the conjugate’s presence in the brain in amount >200 times bigger than that of Van. The conjugates were safe with respect to erythrocyte toxicity (erythrocyte lysis assay). Van in the form of a conjugate with TP10 acquires superior pharmacodynamic and pharmacokinetic.
Rapid analysis of intraperitoneally administered morphine in mouse plasma and brain by microchip electrophoresis-electrochemical detection
Authors: Ollikainen Elisa , Aitta-aho Teemu , Koburg Michaela , Kostiainen Risto , Sikanen Tiina 
Published: March 2019

AbstractAnimal studies remain an essential part of drug discovery sincein vitromodels are not capable of describing the complete living organism. We developed and qualified a microchip electrophoresis-electrochemical detection (MCE-EC) method for rapid analysis of morphine in mouse plasma using a commercial MCE-EC device. Following liquid-liquid extraction (LLE), we achieved within-run precision of 3.7 and 4.5% (coefficient of variation, CV, n = 6) and accuracy of 106.9% and 100.7% at biologically relevant morphine concentrations of 5 and 20 µM in plasma, respectively. The same method was further challenged by morphine detection in mouse brain homogenates with equally good within-run precision (7.8% CV, n = 5) at 1 µM concentration. The qualified method was applied to analyze a set of plasma and brain homogenate samples derived from a behavioral animal study. After intraperitoneal administration of 20 mg/kg morphine hydrochloride, the detected morphine concentrations in plasma were between 6.7 and 17 µM. As expected, the morphine concentrations in the brain were significantly lower,ca. 80–125 nM (280–410 pg morphine/mg dissected brain), and could only be detected after preconcentration achieved during LLE. In all, the microchip-based separation system is proven feasible for rapid analysis of morphine to provide supplementary chemical information to behavioral animal studies.
Comparing the effects of non-homogenous mixing patterns on epidemiological outcomes in equine populations: A mathematical modelling study
Authors: Milwid Rachael M. , O’Sullivan Terri L. , Poljak Zvonimir , Laskowski Marek , Greer Amy L. 
Published: March 2019

AbstractDisease transmission models often assume homogenous mixing. This assumption, however, has the potential to misrepresent the disease dynamics for populations in which contact patterns are non-random. A disease transmission model with an SEIR structure was used to compare the effect of weighted and unweighted empirical equine contact networks to weighted and unweighted theoretical networks generated using random mixing. Equine influenza was used as a case study. Incidence curves generated with the unweighted empirical networks were similar in epidemic duration (5–8 days) and peak incidence (30.8–46.4%). In contrast, the weighted empirical networks resulted in a more pronounced difference between the networks in terms of the epidemic duration (8–15 days) and the peak incidence (5–25%). The incidence curves for the empirical networks were bimodal, while the incidence curves for the theoretical networks were unimodal. The incorporation of vaccination and isolation in the model caused a decrease in the cumulative incidence for each network, however, this effect was only seen at high levels of vaccination and isolation for the complete network. This study highlights the importance of using empirical networks to describe contact patterns within populations that are unlikely to exhibit random mixing such as equine populations.
Giant proximity effect in single-crystalline MgB2 bilayers
Authors: Jung Soon-Gil , Pham Duong , Park Tae-Ho , Choi Han-Yong , Seo Jin Won , Kang Won Nam , Park Tuson 
Published: March 2019

AbstractAlthough giant proximity effect (GPE) can shed important information on understanding superconducting pairing mechanisms and superconducting electronics, reports on the GPE are few because the fabrication of the junctions with GPE is technologically difficult. Here, we report a GPE in the single-crystalline MgB2bilayers (S′/S), where theS′ is the damaged MgB2layer by cobalt (Co)-ion irradiation and theSis the undamaged MgB2layer. Superconducting properties of theS′ is remarkably degraded by the irradiation, whereas those of theSis uninfluenced by the irradiation. The degraded superconductivity in theS′ is fully recovered by increasing the thickness of undamaged MgB2layerSdespite almost ten times larger thickness ~ 95 nm ofS′ than the superconducting coherence lengthξab(0) ~ 8.5 nm of theS, indicating a presence of GPE in theS′/SMgB2bilayers. A diffusion of electrons in theS′ into theScan reduce a pair breaking scattering in theS′, and the similar electronic structures ofS′ andSlayers and a finite attractive electron-electron interaction in theS′ are thought to be origins of unpredicted GPE between the same superconducting materials. Both upper critical field (μ0Hc2) and in-field critical current density (Jc) ofS′/Sbilayers show a significant enhancement, representing a strong correlation betweenS′ andS. These discoveries provide the blue print to the design of the superconducting multilayers for fundamental researches on the mechanism of the GPE as well as their technological applications.
Plant-type pentatricopeptide repeat proteins with a DYW domain drive C-to-U RNA editing in Escherichia coli
Authors: Oldenkott Bastian , Yang Yingying , Lesch Elena , Knoop Volker , Schallenberg-Rüdinger Mareike 
Published: March 2019

AbstractRNA editing converting cytidines into uridines is a hallmark of gene expression in land plant chloroplasts and mitochondria. Pentatricopeptide repeat (PPR) proteins have a key role in target recognition, but the functional editosome in the plant organelles has remained elusive. Here we show that individual Physcomitrella patens DYW-type PPR proteins alone can perform efficient C-to-U editing in Escherichia coli reproducing the moss mitochondrial editing. Single amino acid exchanges in the DYW domain abolish RNA editing, confirming it as the functional cytidine deaminase. The modification of RNA targets and the identification of numerous off-targets in the E. coli transcriptome reveal nucleotide identities critical for RNA recognition and cytidine conversion. The straightforward amenability of the new E. coli setup will accelerate future studies on RNA target recognition through PPRs, on the C-to-U editing deamination machinery and towards future establishment of transcript editing in other genetic systems.
Murine osteoclasts secrete serine protease HtrA1 capable of degrading osteoprotegerin in the bone microenvironment
Authors: Ochiai Nagahiro , Nakachi Yutaka , Yokoo Tomotaka , Ichihara Takahiro , Eriksson Tore , Yonemoto Yuki , Kato Takehiko , Ogata Hitoshi , Fujimoto Natsuko , Kobayashi Yasuhiro , Udagawa Nobuyuki , Kaku Shinsuke , Ueki Tomokazu , Okazaki Yasushi , Takahashi Naoyuki , Suda Tatsuo 
Published: March 2019

AbstractOsteoclasts are multinucleated cells responsible for bone resorption. The differentiation of osteoclasts from bone marrow macrophages (BMMs) is induced by receptor activator of NF-κB ligand (RANKL). Osteoprotegerin (OPG), a decoy receptor of RANKL, inhibits osteoclastogenesis by blocking RANKL signaling. Here we investigated the degradation of OPG in vitro. Osteoclasts, but not BMMs, secreted OPG-degrading enzymes. Using mass spectrometry and RNA-sequencing analysis, we identified high-temperature requirement A serine peptidase 1 (HtrA1) as an OPG-degrading enzyme. HtrA1 did not degrade OPG pre-reduced by dithiothreitol, suggesting that HtrA1 recognizes the three-dimensional structure of OPG. HtrA1 initially cleaved the amide bond between leucine 90 and glutamine 91 of OPG, then degraded OPG into small fragments. Inhibitory activity of OPG on RANKL-induced osteoclastogenesis was suppressed by adding HtrA1 in RAW 264.7 cell cultures. These results suggest that osteoclasts potentially prepare a microenvironment suitable for osteoclastogenesis. HtrA1 may be a novel drug target for osteoporosis.