bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amplicon deep sequencing improves Plasmodium falciparum genotyping in clinical trials of antimalarial drugs
Authors: Gruenberg Maria , Lerch Anita , Beck Hans-Peter , Felger Ingrid 
Published: November 2019

AbstractClinical trials monitoring malaria drug resistance require genotyping of recurrent Plasmodium falciparum parasites to distinguish between treatment failure and new infection occurring during the trial follow up period. Because trial participants usually harbour multi-clonal P. falciparum infections, deep amplicon sequencing (AmpSeq) was employed to improve sensitivity and reliability of minority clone detection. Paired samples from 32 drug trial participants were Illumina deep-sequenced for five molecular markers. Reads were analysed by custom-made software HaplotypR and trial outcomes compared to results from the previous standard genotyping method based on length-polymorphic markers. Diversity of AmpSeq markers in pre-treatment samples was comparable or higher than length-polymorphic markers. AmpSeq was highly reproducible with consistent quantification of co-infecting parasite clones within a host. Outcomes of the three best-performing markers, cpmp, cpp and ama1-D3, agreed in 26/32 (81%) of patients. Discordance between the three markers performed per sample was much lower by AmpSeq (six patients) compared to length-polymorphic markers (eleven patients). Using AmpSeq for discrimination of recrudescence and new infection in antimalarial drug trials provides highly reproducible and robust characterization of clone dynamics during trial follow-up. AmpSeq overcomes limitations inherent to length-polymorphic markers. Regulatory clinical trials of antimalarial drugs will greatly benefit from this unbiased typing method.
Ecological networks: Pursuing the shortest path, however narrow and crooked
Authors: Costa Andrea , Martín González Ana M. , Guizien Katell , Doglioli Andrea M. , Gómez José María , Petrenko Anne A. , Allesina Stefano 
Published: November 2019

AbstractRepresenting data as networks cuts across all sub-disciplines in ecology and evolutionary biology. Besides providing a compact representation of the interconnections between agents, network analysis allows the identification of especially important nodes, according to various metrics that often rely on the calculation of the shortest paths connecting any two nodes. While the interpretation of a shortest paths is straightforward in binary, unweighted networks, whenever weights are reported, the calculation could yield unexpected results. We analyzed 129 studies of ecological networks published in the last decade that use shortest paths, and discovered a methodological inaccuracy related to the edge weights used to calculate shortest paths (and related centrality measures), particularly in interaction networks. Specifically, 49% of the studies do not report sufficient information on the calculation to allow their replication, and 61% of the studies on weighted networks may contain errors in how shortest paths are calculated. Using toy models and empirical ecological data, we show how to transform the data prior to calculation and illustrate the pitfalls that need to be avoided. We conclude by proposing a five-point check-list to foster best-practices in the calculation and reporting of centrality measures in ecology and evolution studies.
The landscape of tiered regulation of breast cancer cell metabolism
Authors: Katzir Rotem , Polat Ibrahim H. , Harel Michal , Katz Shir , Foguet Carles , Selivanov Vitaly A. , Sabatier Philippe , Cascante Marta , Geiger Tamar , Ruppin Eytan 
Published: November 2019

AbstractAltered metabolism is a hallmark of cancer, but little is still known about its regulation. In this study, we measure transcriptomic, proteomic, phospho-proteomic and fluxomics data in a breast cancer cell-line (MCF7) across three different growth conditions. Integrating these multiomics data within a genome scale human metabolic model in combination with machine learning, we systematically chart the different layers of metabolic regulation in breast cancer cells, predicting which enzymes and pathways are regulated at which level. We distinguish between two types of reactions, directly and indirectly regulated.Directly-regulatedreactions include those whose flux is regulated by transcriptomic alterations (~890) or via proteomic or phospho-proteomics alterations (~140) in the enzymes catalyzing them. We term the reactions that currently lack evidence for direct regulation as (putative)indirectly regulated(~930). Many metabolic pathways are predicted to be regulated at different levels, and those may change at different media conditions. Remarkably, we find that the flux of predicted indirectly regulated reactions is strongly coupled to the flux of the predicted directly regulated ones, uncovering a tiered hierarchical organization of breast cancer cell metabolism. Furthermore, the predicted indirectly regulated reactions are predominantly reversible. Taken together, this architecture may facilitate rapid and efficient metabolic reprogramming in response to the varying environmental conditions incurred by the tumor cells. The approach presented lays a conceptual and computational basis for mapping metabolic regulation in additional cancers.
Climate change could overturn bird migration: Transarctic flights and high-latitude residency in a sea ice free Arctic
Authors: Clairbaux Manon , Fort Jérôme , Mathewson Paul , Porter Warren , Strøm Hallvard , Grémillet David 
Published: November 2019

AbstractClimate models predict that by 2050 the Arctic Ocean will be sea ice free each summer. Removing this barrier between the Atlantic and the Pacific will modify a wide range of ecological processes, including bird migration. Using published information, we identified 29 arctic-breeding seabird species, which currently migrate in the North Atlantic and could shift to a transarctic migration towards the North Pacific. We also identified 24 arctic-breeding seabird species which may shift from a migratory strategy to high-arctic year-round residency. To illustrate the biogeographical consequences of such drastic migratory shifts, we performed an in-depth study of little auks (Alle alle), the most numerous artic seabird. Coupling species distribution models and climatic models, we assessed the adequacy of future wintering and breeding areas for transarctic migrants and high-arctic year-round residents. Further, we used a mechanistic bioenergetics model (Niche Mapper), to compare the energetic costs of current little auk migration in the North Atlantic with potential transarctic and high-arctic residency strategies. Surprisingly, our results indicate that transarctic little auk migration, from the North Atlantic towards the North Pacific, may only be half as costly, energetically, than high-arctic residency or migration to the North Atlantic. Our study illustrates how global warming may radically modify the biogeography of migratory species, and provides a general methodological framework linking migratory energetics and spatial ecology.
Tracking capsule activation and crack healing in a microcapsule-based self-healing polymer
Authors: McDonald S. A. , Coban S. B. , Sottos N. R. , Withers P. J. 
Published: November 2019

AbstractStructural polymeric materials incorporating a microencapsulated liquid healing agent demonstrate the ability to autonomously heal cracks. Understanding how an advancing crack interacts with the microcapsules is critical to optimizing performance through tailoring the size, distribution and density of these capsules. For the first time, time-lapse synchrotron X-ray phase contrast computed tomography (CT) has been used to observe in three-dimensions (3D) the dynamic process of crack growth, microcapsule rupture and progressive release of solvent into a crack as it propagates and widens, providing unique insights into the activation and repair process. In this epoxy self-healing material, 150 µm diameter microcapsules within 400 µm of the crack plane are found to rupture and contribute to the healing process, their discharge quantified as a function of crack propagation and distance from the crack plane. Significantly, continued release of solvent takes place to repair the crack as it grows and progressively widens.
Long-term stability of marine dissolved organic carbon emerges from a neutral network of compounds and microbes
Authors: Mentges A. , Feenders C. , Deutsch C. , Blasius B. , Dittmar T. 
Published: November 2019

AbstractDissolved organic carbon (DOC) is the main energy source for marine heterotrophic microorganisms, but a small fraction of DOC resists microbial degradation and accumulates in the ocean. The reason behind this recalcitrance is unknown. We test whether the long-term stability of DOC requires the existence of structurally refractory molecules, using a mechanistic model comprising a diverse network of microbe-substrate interactions. Model experiments reproduce three salient observations, even when all DOC compounds are equally degradable: (i) >15% of an initial DOC pulse resists degradation, but is consumed by microbes if concentrated, (ii) the modelled deep-sea DOC reaches stable concentrations of 30–40 mmolC/m3, and (iii) the mean age of deep-sea DOC is several times the age of deep water with a wide range from <100 to >10,000 years. We conclude that while structurally-recalcitrant molecules exist, they are not required in the model to explain either the amount or longevity of DOC.
Full title: High glucose protects mesenchymal stem cells from metformin-induced apoptosis through the AMPK-mediated mTOR pathway
Authors: He Xiao , Yang Yi , Yao Meng-Wei , Ren Ting-ting , Guo Wei , Li Ling , Xu Xiang 
Published: November 2019

AbstractMicro- and macro-vascular events are directly associated with hyperglycemia in patients with type 2 diabetes mellitus (T2DM), but whether intensive glucose control decreases the risk of diabetic cardiovascular complications remains uncertain. Many studies have confirmed that impaired quality and quantity of mesenchymal stem cells (MSCs) plays a pathogenic role in diabetes. Our previous study found that the abundance of circulating MSCs was significantly decreased in patients with T2DM, which was correlated with the progression of diabetic complications. In addition, metformin-induced MSC apoptosis is one of the reasons for the decreased quantity of endogenous or exogenous MSCs during intensive glucose control. However, the role of glucose in metformin-induced MSC apoptosis during intensive glucose control in T2DM remains unknown. In this study, we found that metformin induces MSC apoptosis during intensive glucose control, while high glucose (standard glucose control) could significantly reverse its adverse effect in an AMPK-mTOR pathway dependent manner. Thus, our results indicate that the poorer clinical benefit of the intensive glucose control strategy may be related to an adverse effect due to metformin-induced MSC apoptosis during intensive glucose control therapy in patients with T2DM.
Spatial and temporal patterns of a pulsed resource dynamically drive the distribution of specialist herbivores
Authors: Doublet Violette , Gidoin Cindy , Lefèvre François , Boivin Thomas 
Published: November 2019

AbstractPatterns and drivers of the spatio-temporal distribution of herbivores are key elements of their ecological and evolutionary impacts on plant populations. Herbivore spatial distributions may be influenced by increased (RCH: resource concentration hypothesis) or decreased (RDH: resource dilution hypothesis) resource densities, but the effect of temporal variations in resource densities on such distributions remains poorly documented. We used a survey of a masting tree species and its seed predators in Southeastern France to address the effect of a host’s pulsed resource on the spatio-temporal distributions of highly specialized insect herbivores feeding on seeds. Variations in both resource and seed predator densities were assessed by estimating seed production and seed infestation rates in focus trees during 10 consecutive years. We found increasing seed infestation rates with decreasing host tree densities in years of low seed production, indicating a RDH pattern of seed predators. However, such pattern was not persistent in years of high seed production during which seed infestation rates did not depend on host tree densities. We showed that temporal variations in resource density can lead to transience of seed predator spatial distribution. This study highlights how predictions of plant-herbivore interactions in natural ecosystems may rely on temporal components underlying RCH and RDH hypotheses.
Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis
Authors: Takenaka Kazuhiro , Tominaga Keiichi , Kanazawa Mimari , Fukushi Koh , Tanaka Takanao , Kanamori Akira , Sugaya Takeshi , Tsuchida Kouhei , Iijima Makoto , Goda Kenichi , Irisawa Atsushi 
Published: November 2019

AbstractWhile immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.
Respiratory tract infections among French Hajj pilgrims from 2014 to 2017
Authors: Hoang Van-Thuan , Ali-Salem Saliha , Belhouchat Khadidja , Meftah Mohammed , Sow Doudou , Dao Thi-Loi , Ly Tran Duc Anh , Drali Tassadit , Ninove Laetitia , Yezli Saber , Alotaibi Badriah , Raoult Didier , Parola Philippe , Pommier de Santi Vincent , Gautret Philippe 
Published: November 2019

AbstractRespiratory tract infections (RTIs) are common among Hajj pilgrims, but risk factors for RTIs and respiratory pathogen acquisition during the Hajj are not clearly identified. Based on previous studies, most frequent pathogens acquired by Hajj pilgrims were investigated: rhinovirus, human coronaviruses, influenza viruses, Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae. 485 pilgrims were included. 82.1% presented with RTIs. Respiratory chronic diseases were associated with cough, Influenza-like illness (ILI) and the acquisition of H. influenzae. Vaccination against invasive pneumococcal diseases (IPD) and influenza was associated with a decrease in the acquisition of S. pneumoniae and prevalence of ILI (aRR = 0.53, 95%CI [0.39–0.73] and aRR = 0.69, 95%CI [0.52–0.92] respectively). Individuals carrying rhinovirus and H. influenzae-S. pneumoniae together were respectively twice and five times more likely to have respiratory symptoms. Individual with H. influenzae-K. pneumoniae carriage were twice (p = 0.04) as likely to develop a cough. The use of disposable handkerchiefs was associated with a decrease in the acquisition of S. aureus (aRR = 0.75, 95%CI [0.57–0.97]). Results could be used to identify pilgrims at increased risk of RTIs and acquisition of respiratory pathogens. Results also confirm the effectiveness of influenza and IPD vaccinations in reducing ILI symptoms and acquisition of S. pneumoniae carriage respectively.
Pharmacogenetics of amfepramone in healthy Mexican subjects reveals potential markers for tailoring pharmacotherapy of obesity: results of a randomised trial
Authors: Gómez-Silva Magdalena , Piñeyro-Garza Everardo , Vargas-Zapata Rigoberto , Gamino-Peña María Elena , León-García Armando , de León Mario Bermúdez , Llerena Adrián , León-Cachón Rafael B. R. 
Published: November 2019

AbstractAmfepramone (AFP) is an appetite-suppressant drug used in the treatment of obesity. Nonetheless, studies on interindividual pharmacokinetic variability and its association with genetic variants are limited. We employed a pharmacokinetic and pharmacogenetic approach to determine possible metabolic phenotypes of AFP and identify genetic markers that could affect the pharmacokinetic variability in a Mexican population. A controlled, randomized, crossover, single-blind, two-treatment, two-period, and two sequence clinical study of AFP (a single 75 mg dose) was conducted in 36 healthy Mexican volunteers who fulfilled the study requirements. Amfepramone plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed using real-time PCR with TaqMan probes. Four AFP metabolizer phenotypes were found in our population: slow, normal, intermediate, and fast. Additionally, two gene polymorphisms, ABCB1-rs1045642 and CYP3A4-rs2242480, had a significant effect on AFP pharmacokinetics (P < 0.05) and were the predictor factors in a log-linear regression model. The ABCB1 and CYP3A4 gene polymorphisms were associated with a fast metabolizer phenotype. These results suggest that metabolism of AFP in the Mexican population is variable. In addition, the genetic variants ABCB1-rs1045642 and CYP3A4-rs2242480 may partially explain the AFP pharmacokinetic variability.
PedMap: a pediatric diseases map generated from clinical big data from Hangzhou, China
Authors: Li Haomin , Yu Gang , Dong Cong , Jia Zheng , An Jiye , Duan Huilong , Shu Qiang 
Published: November 2019

AbstractEpidemiological knowledge of pediatric diseases may improve professionals’ understanding of the pathophysiology of and risk factors for diseases and is also crucial for decision making related to workforce and resource planning in pediatric departments. In this study, a pediatric disease epidemiology knowledgebase called PedMap (http://pedmap.nbscn.org) was constructed from the clinical data from 5 447 202 outpatient visits of 2 189 868 unique patients at a children’s hospital (Hangzhou, China) from 2013 to 2016. The top 100 most-reported pediatric diseases were identified and visualized. These common pediatric diseases were clustered into 4 age groups and 4 seasons. The prevalence, age distribution and co-occurrence diseases for each disease were also visualized. Furthermore, an online prediction tool based on Gaussian regression models was developed to predict pediatric disease incidence based on weather information. PedMap is the first comprehensive epidemiological resource to show the full view of age-related, seasonal, climate-related variations in and co-occurrence patterns of pediatric diseases.
Maritime Aerosol Optical and Microphysical Properties in the South China Sea Under Multi-source Influence
Authors: Zhang Chi , Xu Hua , Li Zhengqiang , Xie Yisong , Li Donghui 
Published: November 2019

AbstractThe South China Sea hosts a wide range of aerosol pollutants with the uneven development of socio-economic and complicated meteorology system. To fill the gap of the maritime aerosol characteristics over the sea, we selected the multi-year ground-based measurements of Taiping Site and Dongsha Site to investigate the optical and microphysical properties. In Taiping, the vast majority of aerosol optical depths (AODs) are less than 0.2, but that of Dongsha shows the wider distribution of AODs from 0 to 0.6. Angstrom Exponent frequency distribution in Taiping peaks at the range of 0.75–1.25 but that has the left-skewed distribution in Taiping Island. Moreover, there is a variation in the coarse-mode volume concentration in Taiping Island but less variation in the fine mode. The seasonal maritime aerosol properties of Taiping and Dongsha have been analyzed that can be employed as a maritime look up table (LUT) kernel in coupled atmospheric retrieval and correction algorithms.
Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile
Authors: Cruite Justin T. , Kovacikova Gabriela , Clark Kenzie A. , Woodbrey Anne K. , Skorupski Karen , Kull F. Jon 
Published: November 2019

AbstractThe AraC/XylS-family transcriptional regulator ToxT is the master virulence activator ofVibrio cholerae, the gram-negative bacterial pathogen that causes the diarrheal disease cholera. Unsaturated fatty acids (UFAs) found in bile inhibit the activity of ToxT. Crystal structures of inhibited ToxT bound to UFA or synthetic inhibitors have been reported, but no structure of ToxT in an active conformation had been determined. Here we present the 2.5 Å structure of ToxT without an inhibitor. The structure suggests release of UFA or inhibitor leads to an increase in flexibility, allowing ToxT to adopt an active conformation that is able to dimerize and bind DNA. Small-angle X-ray scattering was used to validate a structural model of an open ToxT dimer bound to the cholera toxin promoter. The results presented here provide a detailed structural mechanism for virulence gene regulation inV. choleraeby the UFA components of bile and other synthetic ToxT inhibitors.
Single-atom nickel confined nanotube superstructure as support for catalytic wet air oxidation of acetic acid
Authors: Jin Chengyu , Ma Lei , Sun Wenjing , Han Peiwei , Tan Xiangdong , Wu Huiling , Liu Mengyang , Jin Haibo , Wu Zhongshuai , Wei Huangzhao , Sun Chenglin 
Published: November 2019

AbstractSingle-atom confined materials (SACMs) have been widely researched as catalysts in many fields within recent years. However, this class of materials may not only serve as a catalyst but also as a support material for certain reactions. Here we propose a general strategy to use SACMs as supports for tuning loaded noble metal (e.g., Ru) nanoparticles with enhanced catalytic activity. As a proof of concept, a nickel single-atom confined nitrogen-doped carbon nanotube (NCNT) superstructure is prepared as a support to load noble metal Ru for catalytic wet air oxidation of acetic acid. Improved catalytic activity with a mineralization rate of ~97.5% is achieved. Further, adsorption configurations based on DFT calculations also confirm our deduction that the introduction of single-atom Ni changes the intrinsic property of NCNTs and affects the loaded active Ru nanoparticles.