bluuebunny/crossref_metadata_2025_split huggingface dataset:
High residual carriage of vaccine-serotype Streptococcus pneumoniae after introduction of pneumococcal conjugate vaccine in Malawi
Authors: Swarthout Todd D. , Fronterre Claudio , Lourenço José , Obolski Uri , Gori Andrea , Bar-Zeev Naor , Everett Dean , Kamng’ona Arox W. , Mwalukomo Thandie S. , Mataya Andrew A. , Mwansambo Charles , Banda Marjory , Gupta Sunetra , Diggle Peter , French Neil , Heyderman Robert S. 
Published: May 2020

AbstractThere are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6–7.1 years after Malawi’s 2011 PCV13 introduction. Carriage decay rate is analysed using non-linear regression. Despite evidence of reduction in VT carriage over the study period, there is high persistent residual carriage. This includes among PCV-vaccinated children 3–5-year-old (16.1% relative reduction from 19.9% to 16.7%); PCV-unvaccinated children 6–8-year-old (40.5% reduction from 26.4% to 15.7%); HIV-infected adults 18-40-years-old on antiretroviral therapy (41.4% reduction from 15.2% to 8.9%). VT carriage prevalence half-life is similar among PCV-vaccinated and PCV-unvaccinated children (3.26 and 3.34 years, respectively). Compared with high-income settings, there is high residual VT carriage 3.6–7.1 years after PCV introduction. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns, is required.
Disruption of ATRX-RNA interactions uncovers roles in ATRX localization and PRC2 function
Authors: Ren Wenqing , Medeiros Nicole , Warneford-Thomson Robert , Wulfridge Phillip , Yan Qingqing , Bian Joyce , Sidoli Simone , Garcia Benjamin A. , Skordalakes Emmanuel , Joyce Eric , Bonasio Roberto , Sarma Kavitha 
Published: May 2020

AbstractHeterochromatin in the eukaryotic genome is rigorously controlled by the concerted action of protein factors and RNAs. Here, we investigate the RNA binding function of ATRX, a chromatin remodeler with roles in silencing of repetitive regions of the genome and in recruitment of the polycomb repressive complex 2 (PRC2). We identify ATRX RNA binding regions (RBRs) and discover that the major ATRX RBR lies within the N-terminal region of the protein, distinct from its PHD and helicase domains. Deletion of this ATRX RBR (ATRXΔRBR) compromises ATRX interactions with RNAs in vitro and in vivo and alters its chromatin binding properties. Genome-wide studies reveal that loss of RNA interactions results in a redistribution of ATRX on chromatin. Finally, our studies identify a role for ATRX-RNA interactions in regulating PRC2 localization to a subset of polycomb target genes.
In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever
Authors: Baral Prabin , Pavadai Elumalai , Gerstman Bernard S. , Chapagain Prem P. 
Published: May 2020

AbstractLassa virus (LASV), a member of the Arenaviridae, is an ambisense RNA virus that causes severe hemorrhagic fever with a high fatality rate in humans in West and Central Africa. Currently, no FDA approved drugs or vaccines are available for the treatment of LASV fever. The LASV glycoprotein complex (GP) is a promising target for vaccine or drug development. It is situated on the virion envelope and plays key roles in LASV growth, cell tropism, host range, and pathogenicity. In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In addition, many sequence- and structure-based computational prediction tools were used to identify LASV GP B-cell epitopes. The predicted T- and B-cell epitopes were further filtered based on the consensus approach that resulted in the identification of thirty new epitopes that have not been previously tested experimentally. Epitope-allele complexes were obtained for selected strongly binding alleles to the MHC-I T-cell epitopes using molecular docking and the complexes were relaxed with molecular dynamics simulations to investigate the interaction and dynamics of the epitope-allele complexes. These predictions provide guidance to the experimental investigations and validation of the epitopes with the potential for stimulating T-cell responses and B-cell antibodies against LASV and allow the design and development of LASV vaccines.
Robust assessment of the time of emergence of precipitation change in West Africa
Authors: Gaetani Marco , Janicot Serge , Vrac Mathieu , Famien Adjoua Moise , Sultan Benjamin 
Published: May 2020

AbstractThe time of emergence (TOE) of climate change is defined as the time when a new climate state emerges from a prior one. TOE assessment is particularly relevant in West Africa, a region highly threatened by climate change and urgently needing trustworthy climate predictions. In this paper, the TOE of precipitation change in West Africa is assessed for the first time, by analyzing 6 precipitation metrics (cumulated precipitation, number of wet and very wet days, onset and length of the rainy season) computed from the output of 29 state-of-the-art climate models. In West Sahel, climate conditions characterized by reduced occurrence of wet days are likely to emerge before 2036, leading to the possible emergence of a dryer climate in 2028–2052. In East Sahel, a wetter precipitation regime characterized by increased occurrence of very wet days is likely to emerge before 2054. Results do not provide a clear indication about a possible climate shift in the onset and length of the rainy season. Although uncertainty in climate model future projections still limits the robust determination of TOE locally, this study provides reliable time constraints to the expected climate shift in West Africa at the sub-regional scale, supporting adaptation measures to the future change in the precipitation regime.
Spatial early warning signals of social and epidemiological tipping points in a coupled behaviour-disease network
Authors: Phillips Brendon , Anand Madhur , Bauch Chris T. 
Published: May 2020

AbstractThe resurgence of infectious diseases due to vaccine refusal has highlighted the role of interactions between disease dynamics and the spread of vaccine opinion on social networks. Shifts between disease elimination and outbreak regimes often occur through tipping points. It is known that tipping points can be predicted by early warning signals (EWS) based on characteristic dynamics near the critical transition, but the study of EWS in coupled behaviour-disease networks has received little attention. Here, we test several EWS indicators measuring spatial coherence and autocorrelation for their ability to predict a critical transition corresponding to disease outbreaks and vaccine refusal in a multiplex network model. The model couples paediatric infectious disease spread through a contact network to binary opinion dynamics of vaccine opinion on a social network. Through change point detection, we find that mutual information and join count indicators provided the best EWS. We also show the paediatric infectious disease natural history generates a discrepancy between population-level vaccine opinions and vaccine immunity status, such that transitions in the social network may occur before epidemiological transitions. These results suggest that monitoring social media for EWS of paediatric infectious disease outbreaks using these spatial indicators could be successful.
Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish
Authors: Bassi Ivan , Luzzani Francesca , Marelli Federica , Vezzoli Valeria , Cotellessa Ludovica , Prober David A. , Persani Luca , Gothilf Yoav , Bonomi Marco 
Published: May 2020

AbstractProkineticin receptors (PROKR1 and PROKR2) are G protein-coupled receptors which control human central and peripheral reproductive processes. Importantly, allelic variants of PROKR2 in humans are associated with altered migration of GnRH neurons, resulting in congenital hypogonadotropic hypogonadism (CHH), a heterogeneous disease characterized by delayed/absent puberty and/or infertility. Although this association is established in humans, murine models failed to fully recapitulate the reproductive and olfactory phenotypes observed in patients harboring PROKR2 mutations. Here, taking advantage of zebrafish model we investigated the role of prokr1b (ortholog of human PROKR2) during early stages of GnRH neuronal migration. Real-Time PCR and whole mount in situ hybridization assays indicate that prokr1b spatial-temporal expression is consistent with gnrh3. Moreover, knockdown and knockout of prokr1b altered the correct development of GnRH3 fibers, a phenotype that is rescued by injection of prokr1b mRNA. These results suggest that prokr1b regulates the development of the GnRH3 system in zebrafish. Analysis of gonads development and mating experiments indicate that prokr1b is not required for fertility in zebrafish, although its loss determine changes also at the testis level. Altogether, our results support the thesis of a divergent evolution in the control of vertebrate reproduction and provide a useful in vivo model for deciphering the mechanisms underlying the effect of PROKR2 allelic variants on CHH.
Proteomics-Based Approach Identifies Altered ER Domain Properties by ALS-Linked VAPB Mutation
Authors: Yamanaka Tomoyuki , Nishiyama Risa , Shimogori Tomomi , Nukina Nobuyuki 
Published: May 2020

AbstractAn ER transmembrane protein, vesicle-associated membrane protein-associated protein B (VAPB), binds to several organelle-resident membrane proteins to mediate ER-organelle tethering. Mutation in amyotrophic lateral sclerosis (ALS) induces protein misfolding and aggregation, leading to ER disorganization. Gain or loss of function is suggested for VAPB mutation, however comprehensive study focusing on VAPB-ER domain has yet been performed. We here conducted proteomic characterization of the ER containing VAPB and its ALS-linked P56S mutant. For this purpose, we first optimized the proteomics of different ER domains immuno-isolated from cultured cells, and identified ER sheet- and tubule-specific proteomes. By using these as references, we found that VAPB-ER proteome had intermediate ER domain properties but its tubular property was specifically decreased by its mutation. Biochemical, immunofluorescence and proximity ligation assays suggested this was mediated by delocalization of VAPB from ER tubules. The VAPB-ER proteomics further suggested reduced incorporation of multiple proteins located in different organelles, which was confirmed by proximity ligation assay. Taken together, our proteomics-based approach indicates altered ER domain properties and impaired ER-organelle tethering by VAPB mutation.
Rapid identification of pathogens, antibiotic resistance genes and plasmids in blood cultures by nanopore sequencing
Authors: Taxt Arne M. , Avershina Ekaterina , Frye Stephan A. , Naseer Umaer , Ahmad Rafi 
Published: May 2020

AbstractBloodstream infections (BSI) and sepsis are major causes of morbidity and mortality worldwide. Blood culture-based diagnostics usually requires 1–2 days for identification of bacterial agent and an additional 2–3 days for phenotypic determination of antibiotic susceptibility pattern. With the escalating burden of antimicrobial resistance (AMR) rapid diagnostics becomes increasingly important to secure adequate antibiotic therapy. Real-time whole genome sequencing represents a genotypic diagnostic approach with the ability to rapidly identify pathogens and AMR-encoding genes. Here we have used nanopore sequencing of bacterial DNA extracted from positive blood cultures for identification of pathogens, detection of plasmids and AMR-encoding genes. To our knowledge, this is the first study to gather the above-mentioned information from nanopore sequencing and conduct a comprehensive analysis for diagnostic purposes in real-time. Identification of pathogens was possible after 10 minutes of sequencing and all predefined AMR-encoding genes and plasmids from monoculture experiments were detected within one hour using raw nanopore sequencing data. Furthermore, we demonstrate the correct identification of plasmids and blaCTX-M subtypes using de novo assembled nanopore contigs. Results from this study hold great promise for future applications in clinical microbiology and for health care surveillance purposes.
Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice
Authors: López-Escobar Beatriz , Fernández-Torres Rut , Vargas-López Viviana , Villar-Navarro Mercedes , Rybkina Tatyana , Rivas-Infante Eloy , Hernández-Viñas Ayleen , Álvarez del Vayo Concepción , Caro-Vega José , Sánchez-Alcázar José A. , González-Meneses Antonio , Carrión M. Ángel , Ybot-González Patricia 
Published: May 2020

AbstractThe use of first and second generation antiepileptic drugs during pregnancy doubles the risk of major congenital malformations and other teratogenic defects. Lacosamide (LCM) is a third-generation antiepileptic drug that interacts with collapsing response mediator protein 2, a protein that has been associated with neurodevelopmental diseases like schizophrenia. The aim of this study was to test the potential teratogenic effects of LCM on developing embryos and its effects on behavioural/histological alterations in adult mice. We administered LCM to pregnant mice, assessing its presence, and that of related compounds, in the mothers’ serum and in embryonic tissues using liquid chromatography coupled to quadrupole/time of flight mass spectrometry detection. Embryo morphology was evaluated, and immunohistochemistry was performed on adult offspring. Behavioural studies were carried out during the first two postnatal weeks and on adult mice. We found a high incidence of embryonic lethality and malformations in mice exposed to LCM during embryonic development. Neonatal mice born to dams treated with LCM during gestation displayed clear psychomotor delay and behavioural and morphological alterations in the prefrontal cortex, hippocampus and amygdala that were associated with behaviours associated with schizophrenia spectrum disorders in adulthood. We conclude that LCM and its metabolites may have teratogenic effects on the developing embryos, reflected in embryonic lethality and malformations, as well as behavioural and histological alterations in adult mice that resemble those presented by patients with schizophrenia.
Multiparametric Mechanistic Profiling of Inotropic Drugs in Adult Human Primary Cardiomyocytes
Authors: Abi-Gerges Najah , Indersmitten Tim , Truong Ky , Nguyen William , Ratchada Phachareeya , Nguyen Nathalie , Page Guy , Miller Paul E. , Ghetti Andre 
Published: May 2020

AbstractEffects of non-cardiac drugs on cardiac contractility can lead to serious adverse events. Furthermore, programs aimed at treating heart failure have had limited success and this therapeutic area remains a major unmet medical need. The challenges in assessing drug effect on cardiac contractility point to the fundamental translational value of the current preclinical models. Therefore, we sought to develop an adult human primary cardiomyocyte contractility model that has the potential to provide a predictive preclinical approach for simultaneously predicting drug-induced inotropic effect (sarcomere shortening) and generating multi-parameter data to profile different mechanisms of action based on cluster analysis of a set of 12 contractility parameters. We report that 17 positive and 9 negative inotropes covering diverse mechanisms of action exerted concentration-dependent increases and decreases in sarcomere shortening, respectively. Interestingly, the multiparametric readout allowed for the differentiation of inotropes operating via distinct mechanisms. Hierarchical clustering of contractility transient parameters, coupled with principal component analysis, enabled the classification of subsets of both positive as well as negative inotropes, in a mechanism-related mode. Thus, human cardiomyocyte contractility model could accurately facilitate informed mechanistic-based decision making, risk management and discovery of molecules with the most desirable pharmacological profile for the correction of heart failure.
Deconvolution of conformational exchange from Raman spectra of aqueous RNA nucleosides
Authors: Wilson Alex L. , Outeiral Carlos , Dowd Sarah E. , Doig Andrew J. , Popelier Paul L. A. , Waltho Jonathan P. , Almond Andrew 
Published: May 2020

AbstractRibonucleic acids (RNAs) are key to the central dogma of molecular biology. While Raman spectroscopy holds great potential for studying RNA conformational dynamics, current computational Raman prediction and assignment methods are limited in terms of system size and inclusion of conformational exchange. Here, a framework is presented that predicts Raman spectra using mixtures of sub-spectra corresponding to major conformers calculated using classical and ab initio molecular dynamics. Experimental optimization allowed purines and pyrimidines to be characterized as predominantly syn and anti, respectively, and ribose into exchange between equivalent south and north populations. These measurements are in excellent agreement with Raman spectroscopy of ribonucleosides, and previous experimental and computational results. This framework provides a measure of ribonucleoside solution populations and conformational exchange in RNA subunits. It complements other experimental techniques and could be extended to other molecules, such as proteins and carbohydrates, enabling biological insights and providing a new analytical tool.
Liraglutide Ameliorates Lipotoxicity-Induced Oxidative Stress by
Activating the NRF2 Pathway in HepG2 Cells
Authors: Zhu Chong-gui , Luo Ying , Wang Hao , Li Jun-Yi , Yang Jie , Liu Ya-xin , Qu Hui-qi , Wang Bao-li , Zhu Mei 
Published: May 2020

AbstractAlthough glucagon-like peptide-1 (GLP-1) analogue has been reported to suppress
oxidative stress in non-alcoholic fatty liver disease (NAFLD), an effective
therapeutic agent for NAFLD is currently unavailable. Therefore, in this study,
we aimed to investigate the protective effects of the GLP-1 analogue liraglutide
against lipotoxicity-induced oxidative stress in HepG2 cells and to elucidate
the underlying mechanisms. HepG2 cells were cultured for 48 hours and treated
with a free fatty acid (FFA) mixture: FFA mixture and liraglutide or FFA
mixture, liraglutide, and exendin (9–39). Lipid accumulation was
examined by oil red O staining. Oxidative stress was assessed by measuring the
levels of intracellular reactive oxygen species using
2′,7′-dichlorofluorescein diacetate and thiobarbituric
acid-reactive substances, whereas antioxidant capacity was assessed by measuring
the activity of superoxide dismutase and catalase. Expression of the nuclear
factor erythroid-2-related factor 2 (NRF2) gene and the genes encoding
antioxidant enzymes was analyzed using quantitative RT-PCR. Cellular and nuclear
NRF2 expression levels were assessed using immunofluorescence cell staining and
western blotting. Liraglutide treatment reduced high fat-induced lipid formation
and the levels of oxidative stress markers and increased antioxidant enzyme
activity in HepG2 cells. Liraglutide treatment increased the mRNA expression of
NRF2 target genes, induced NRF2 nuclear translocation, and increased nuclear
NRF2 levels without altering NRF2 mRNA expression. Collectively, these
results indicate that liraglutide exhibits a protective effect against
lipotoxicity-induced oxidative stress, possibly via modulation of NRF2 and
expression of antioxidant enzymes in liver cells.
The effect of temperature change on fluoride uptake from a mouthrinse by enamel specimens
Authors: Baglar Serdar , Nalcaci Adil , Tastekin Mustafa 
Published: May 2020

ABSTRACTObjective: The aim of this study was to examine the effect of temperature on fluoride uptake by enamel specimens from a 0.05% NaF-fluoridated mouthrinse (Oral-B Advantage; Oral-B Laboratories, Newbridge, UK).Methods: Enamel specimens were prepared from extracted human maxillary central incisors. A fluoride-specific ion electrode was used to measure the uptake from a 2 ppm fluoride solution containing 50.0 mL of distilled water, total ion strength adjustment buffer, and fluoridated rinse at 3 different temperatures (room temperature, 25°C; human body temperature, 37°C; hyper-fever temperature, 43°C). One-way analysis of variance and least significant difference were used to assess intragroup and intergroup differences (P<.05).Results: The study found that both the amount and the rate of fluoride uptake increased significantly with increase in temperature. This effect was particularly noticeable at 43°C.Conclusions: The temperature of the NaF mouthrinse may easily and safely be increased beyond room temperature by placing a container of the NaF mouthrinse in a bowl of hot water, allowing greater fluoride penetration into the enamel from the mouthrinse when used at home as a routine prophylactic agent. (Eur J Dent 2012;6:361-369)
Clinical, radiographic, diagnostic and cephalometric features of pycnodysostosis in comparison with Turkish cephalometric norms: A case report
Authors: Kamak Hasan , Kamak Gulen , Yavuz Ibrahim 
Published: May 2020

ABSTRACTPycnodysostosis is a rare genetic disorder and was first described in 1962 by Maroteaux and Lamy. The incidence of this anomaly is estimated to be 1.7 per 1 million births. The principal characteristics of this disorder are short stature, prominent eyes with blue sclera, beaked nose, cranial dysplasia, exposed fontanelles and cranial sutures, clavicular dysplasia, total/partial dysplasia of the terminal phalanges, obtused mandibular gonial angle, and generally increased bone density. Some features of pycnodysostosis are similar to osteopetrosis and cleidocranial dysostosis. Therefore, it must be distinguished from osteopetrosis and cleidocranial dysostosis in order to diagnose it in individuals of a younger age.The aims of this case report were to show the clinical, radiographic, and diagnostic features, as well as the cephalometric characteristics of pycnodysostosis in comparison with Turkish cephalometric norms. (Eur J Dent 2012;6:454-456)
Revision Surgery of the Cleft Palate
Authors: Hu Shirley , Levinson Jared , Rousso Joseph J. 
Published: May 2020

AbstractCleft palate repairs often require secondary surgeries and/or revisions for a variety of reasons. The most common causes are symptomatic oronasal fistulas and velopharyngeal insufficiency. Complications from primary surgery, such as wound dehiscence, infection, and hematomas, contribute to the relatively high rate of revision surgery. Prevention of postoperative complications that may lead to fistula or velopharyngeal insufficiency is key, and many techniques have been described that have reportedly decreased the incidence of secondary surgery. Management varies depending on the nature of the fistulous defect and the type of velopharyngeal insufficiency. Numerous surgical options exist to fix this deficiency.
Surgery of the Palatomaxillary Structure
Authors: Jategaonkar Ameya A. , Kaul Vivian F. , Lee Eric , Genden Eric M. 
Published: May 2020

AbstractThe palatomaxillary structure plays critical roles in both form and function of the midface. Surgical defects of the palate and maxilla can be associated with significant morbidity and deformity. Various defect classification systems have been used to assist in reconstruction and rehabilitation. Reconstructive options include prosthetic rehabilitation, local flaps, and free tissue transfer. Here, we review the functional and surgical anatomy of the palatomaxillary complex, defect classification systems, and provide an overview of reconstructive options.