bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐Time Monitoring of Ionosphere VTEC Using Multi‐GNSS Carrier‐Phase Observations and B‐Splines
Authors: Erdogan Eren , Schmidt Michael , Goss Andreas , Görres Barbara , Seitz Florian
Published: September 2021

Monitoring the Vertical Total Electron Content (VTEC) of the ionosphere is important for applications ranging from navigation to detection of space weather events. Therefore, emerging efforts have been made by several analysis centers to estimate the VTEC using different approaches in real‐time. Global Navigation Satellite Systems (GNSS) is a crucial technology for ionosphere modeling due to its worldwide distributed receivers, high temporal resolution, and low latency data dissemination capability. The selection of a convenient approach to extract ionosphere information from GNSS and the representation of VTEC by an appropriate mathematical model are essential factors for providing fast and accurate ionosphere products. Contrarily to the widespread phase‐leveling method, which uses noisy and erroneous code measurements, the modeling concept in this paper utilizes pure carrier‐phase measurements. Measurements acquired through the International GNSS Service (IGS) real‐time service in Radio Technical Commission for Maritime Services format are from GPS, GLONASS, and GALILEO. The measurement biases, including the ambiguity of carrier‐phase measurements, are simultaneously estimated along with VTEC model parameters. In our approach, VTEC is represented by B‐spline expansions embedded into a Kalman filter. Due to their localizing feature, B‐splines form a highly sparse structure in the filter measurement model. Thus, matrix operations for large‐scale problems can be performed fast using sparse matrix operations, as is done in this study. The differential slant total electron content (dSTEC) analysis and the comparison with Jason‐3 altimetry VTEC were performed for validation within selected periods in 2019. The dSTEC analysis shows that the quality of the generated real‐time VTEC maps slightly outperforms those provided by the other IGS analysis centers.
Distributional Regression Forests Approach to Regional Frequency Analysis With Partial Duration Series
Authors: Kiran K. G. , Srinivas V. V.
Published: September 2021

Regional flood frequency analysis (RFFA) is widely used to quantify flood risk at ungauged and sparsely gauged locations. There are minimal attempts to use partial duration series (PDS) for RFFA, though the use of PDS instead of widely used annual maximum series (AMS) can offer some advantages. This article contributes two novel random/regression forests (RFs)‐based methodologies, namely generalized pareto distribution (GPD)‐based distributional RFs (DRFs) and multivariate RFs (MVRFs), for RFFA with PDS. The RFs facilitate modeling interactions between predictors and their complex relationships with the predictands without explicitly specifying them. The DRFs and MVRFs comprise an ensemble of corresponding regression trees, each constructed by recursive binary partitioning of the feature space into meaningful segments. The proposed DRFs account for the sampling uncertainty of PDS in the partitioning and parameter estimation. In DRFs (MVRFs), quantile estimates for an ungauged site are obtained using maximum likelihood estimates (expected values) of GPD parameters corresponding to the segments to which the site belongs. The potential of DRFs and MVRFs relative to two recently proposed techniques (univariate RFs‐based quantile regression, generalized additive model based on GPD) is demonstrated through Monte‐Carlo simulation experiments and a study on 1,031 watersheds in the United States. The key features influencing scale and shape parameters of GPD fitted to PDS of the watersheds are identified as drainage area and 24‐hr rainfall intensity corresponding to 2‐year return period, respectively. Those identified for shape parameter differ from key features known based on analysis with AMS and generalized extreme value distribution.
Do shapes have feelings? Social attribution in children with autism spectrum disorder and attention-deficit/hyperactivity disorder
Authors: Vandewouw Marlee M. , Safar Kristina , Mossad Sarah I. , Lu Julie , Lerch Jason P. , Anagnostou Evdokia , Taylor Margot J.
Published: September 2021

Theory of mind (ToM) deficits are common in children with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which contribute to their social and cognitive difficulties. The social attribution task (SAT) involves geometrical shapes moving in patterns that depict social interactions and is known to recruit brain regions from the classic ToM network. To better understand ToM in ASD and ADHD children, we examined the neural correlates using the SAT and functional magnetic resonance imaging (fMRI) in a cohort of 200 children: ASD (N = 76), ADHD (N = 74) and typically developing (TD; N = 50) (4–19 years). In the scanner, participants were presented with SAT videos corresponding to social help, social threat, and random conditions. Contrasting social vs. random, the ASD compared with TD children showed atypical activation in ToM brain areas—the middle temporal and anterior cingulate gyri. In the social help vs. social threat condition, atypical activation of the bilateral middle cingulate and right supramarginal and superior temporal gyri was shared across the NDD children, with between-diagnosis differences only being observed in the right fusiform. Data-driven subgrouping identified two distinct subgroups spanning all groups that differed in both their clinical characteristics and brain–behaviour relations with ToM ability.
Lenalidomide in combination with R-CHOP produces high response rates and progression-free survival in new, untreated diffuse large B-cell lymphoma transformed from follicular lymphoma: results from the Phase 2 MC078E study
Authors: Desai Sanjal H. , LaPlant Betsy , Macon William R. , King Rebecca L. , Wang Yucai , Inwards David J. , Micallef Ivana , Johnston Patrick B. , Porrata Luis F. , Ansell Stephen M. , Habermann Thomas M. , Witzig Thomas E. , Nowakowski Grzegorz S.
Published: September 2021

Diffuse large B-cell lymphoma (DLBCL), either concurrent with or transformed from follicular lymphoma (FL) is often excluded from clinical trials. Lenalidomide has response rates of 45% in relapsed transformed DLBCL. Herein we present an analysis of MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with untreated transformed/concurrent DLBCL (NCT00670358). Adult patients with transformed or concurrent DLBCL were included. Patients received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with lenalidomide 25 mg days 1–10 of each cycle. The primary outcome was progression-free survival (PFS) at 24 months. Secondary outcomes were response rates, event-free survival (EFS), and overall survival (OS). Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. The median age was 64 (24–80) years, 18 (54%) were male, 25 (76%) were concurrent and 8 (24%) were transformed DLBCL. The PFS, EFS, and OS rates at 24 months were 84.4% (CI95: 67.2–94.7%), 84.5% (CI95: 72.9–98%), and 97.0% (CI95: 91.3–100%), respectively. R2CHOP is effective in concurrent and transformed DLBCL. The study supports the inclusion of anthracycline-naive transformed and concurrent DLBCL in future clinical trials of novel immunomodulatory analogues.
Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition
Authors: Junk David , Krämer Sebastian , Broschewitz Johannes , Laura Hennig , Massa Chiara , Moulla Yousef , Hoang Ngoc Anh , Monecke Astrid , Eichfeld Uwe , Bechmann Ingo , Lordick Florian , Seliger Barbara , Kallendrusch Sonja
Published: September 2021

Despite novel immunotherapies being approved and established for the treatment of non-small cell lung cancer (NSCLC), ex vivo models predicting individual patients’ responses to immunotherapies are missing. Especially immune modulating therapies with moderate response rates urge for biomarkers and/or assays to determine individual prediction of treatment response and investigate resistance mechanisms. Here, we describe a standardized ex vivo tissue culture model to investigate individual tumor responses. NSCLC tissue cultures preserve morphological characteristics of the baseline tumor specimen for up to 12 days ex vivo and also maintain T-cell function for up to 10 days ex vivo. A semi-automated analysis of proliferating and apoptotic tumor cells was used to evaluate tissue responses to the PD-1 inhibitor nivolumab (n = 12), from which two cases could be successfully correlated to the clinical outcome. T-cell responses upon nivolumab treatment were investigated by flow cytometry and multispectral imaging. Alterations in the frequency of the Treg population and reorganization of tumor tissues could be correlated to nivolumab responsiveness ex vivo. Thus, our findings not only demonstrate the functionality of T cells in NSCLC slice cultures up to 10 days ex vivo, but also suggests this model for stratifying patients for treatment selection and to investigate in depth the tumor-associated T-cell regulation.
Multi-generation genomic prediction of maize yield using parametric and non-parametric sparse selection indices
Authors: Lopez-Cruz Marco , Beyene Yoseph , Gowda Manje , Crossa Jose , Pérez-Rodríguez Paulino , de los Campos Gustavo
Published: September 2021

Genomic prediction models are often calibrated using multi-generation data. Over time, as data accumulates, training data sets become increasingly heterogeneous. Differences in allele frequency and linkage disequilibrium patterns between the training and prediction genotypes may limit prediction accuracy. This leads to the question of whether all available data or a subset of it should be used to calibrate genomic prediction models. Previous research on training set optimization has focused on identifying a subset of the available data that is optimal for a given prediction set. However, this approach does not contemplate the possibility that different training sets may be optimal for different prediction genotypes. To address this problem, we recently introduced a sparse selection index (SSI) that identifies an optimal training set for each individual in a prediction set. Using additive genomic relationships, the SSI can provide increased accuracy relative to genomic-BLUP (GBLUP). Non-parametric genomic models using Gaussian kernels (KBLUP) have, in some cases, yielded higher prediction accuracies than standard additive models. Therefore, here we studied whether combining SSIs and kernel methods could further improve prediction accuracy when training genomic models using multi-generation data. Using four years of doubled haploid maize data from the International Maize and Wheat Improvement Center (CIMMYT), we found that when predicting grain yield the KBLUP outperformed the GBLUP, and that using SSI with additive relationships (GSSI) lead to 5–17% increases in accuracy, relative to the GBLUP. However, differences in prediction accuracy between the KBLUP and the kernel-based SSI were smaller and not always significant.
Dynamic carbon flux network of a diverse marine microbial community
Authors: Mayerhofer Marvin M , Eigemann Falk , Lackner Carsten , Hoffmann Jutta , Hellweger Ferdi L
Published: September 2021

The functioning of microbial ecosystems has important consequences from global climate to human health, but quantitative mechanistic understanding remains elusive. The components of microbial ecosystems can now be observed at high resolution, but interactions still have to be inferred e.g., a time-series may show a bloom of bacteria X followed by virus Y suggesting they interact. Existing inference approaches are mostly empirical, like correlation networks, which are not mechanistically constrained and do not provide quantitative mass fluxes, and thus have limited utility. We developed an inference method, where a mechanistic model with hundreds of species and thousands of parameters is calibrated to time series data. The large scale, nonlinearity and feedbacks pose a challenging optimization problem, which is overcome using a novel procedure that mimics natural speciation or diversification e.g., stepwise increase of bacteria species. The method allows for curation using species-level information from e.g., physiological experiments or genome sequences. The product is a mass-balancing, mechanistically-constrained, quantitative representation of the ecosystem. We apply the method to characterize phytoplankton—heterotrophic bacteria interactions via dissolved organic matter in a marine system. The resulting model predicts quantitative fluxes for each interaction and time point (e.g., 0.16 µmolC/L/d of chrysolaminarin to Polaribacter on April 16, 2009). At the system level, the flux network shows a strong correlation between the abundance of bacteria species and their carbon flux during blooms, with copiotrophs being relatively more important than oligotrophs. However, oligotrophs, like SAR11, are unexpectedly high carbon processors for weeks into blooms, due to their higher biomass. The fraction of exudates (vs. grazing/death products) in the DOM pool decreases during blooms, and they are preferentially consumed by oligotrophs. In addition, functional similarity of phytoplankton i.e., what they produce, decouples their association with heterotrophs. The methodology is applicable to other microbial ecosystems, like human microbiome or wastewater treatment plants.
Framework nucleic acid programmed combinatorial delivery nanocarriers for parallel and multiplexed analysis
Authors: Feng Yinghui , Liu Qi , Chen Miao , Zhao Xinyi , Wang Lumin , Liu Longfei , Chen Xiaoqing
Published: September 2021

An FNA-programmed strategy was proposed to develop nanocarriers to precisely and independently package multiple cargos in vitro and in vivo, thereby enabling multiplexed analysis, as well as favorable imaging and discrimination of different cells.
Excited-state engineering of oligothiophenes via phosphorus chemistry towards strong fluorescent materials
Authors: Yang Zi , Zhang Zhikai , Xue Cece , Yang Kai , Gao Rong , Yu Na , Ren Yi
Published: September 2021

Applying simple, rich and effective P-chemistry to regulate the symmetry breaking charge transfer of P-bridged oligothiophenes provides a powerful strategy for designing strong light-emitting molecules.
Bifunctional application of La3BWO9:Bi3+,Sm3+ phosphors with strong orange-red emission and sensitive temperature sensing properties
Authors: Ran Weiguang , Sun Guangshi , Ma Xiaoli , Zhang Liyun , Yu Jae Su , Noh Hyeon Mi , Choi Byung Chun , Jeong Jung Hyun , Yan Tingjiang
Published: September 2021

Through a solid-phase reaction technique, Sm3+ and Bi3+ co-doped La3BWO9 phosphors with high emission intensity and sensitive temperature sensing properties have been successfully synthesized.
Discovery of a naturally occurring broad-spectrum inhibitor against gut bacterial β-glucuronidases fromGinkgo biloba
Authors: Bai Yue , Chen Lu , Wang Pan-Pan , Tang Yu-Qiang , Wu Da-Chang , Zhang Cui-Li , Zhou Qi , Yan Ru , Hou Jie
Published: September 2021

Gut bacterial β-glucuronidases (GUS) play an important role in deconjugation of variousO-glucuronides, which are tightly linked to the drug-induced intestinal toxicity.
Probing the conjugation of epigallocatechin gallate with β-lactoglobulin and its in vivo desensitization efficiency
Authors: Zhang Xiaoning , Li Sining , Shao Xiaoqing , Li Meifeng , Hemar Yacine
Published: September 2021

The conjugation of EGCG on βLg decreased βLg's IgE combining capacity, which in turn can be probed as a possible approach for desensitization to allergens.
Visible-light-mediated three-component Minisci reaction for heteroarylethyl alcohols synthesis
Authors: Dong Jianyang , Yue Fuyang , Liu Jianhua , Song Hongjian , Liu Yuxiu , Wang Qingmin
Published: September 2021

A mild, modular, practical Minisci reaction for catalytic synthesis of heteroarylethyl alcohols via sequential addition of H2O and N-heteroarenes across olefinic double bonds is reported.
Conformational isomerism involving the carboxylate groups of a linker in metal organic frameworks and its distinctive influence on the detection of ketones
Authors: Kumar Sandeep , Bhambri Himanshi , Mandal Sanjay K.
Published: September 2021

Selective sensing of various ketones by Zn(ii) based conformational MOF isomers.
A mini-review of carbon-resistant anode materials for solid oxide fuel cells
Authors: Tao Zetian , Fu Min , Liu Yong
Published: September 2021

A comprehensive overview is presented of recent developments as well as trends of carbon-resistant anode materials using hydrocarbon as fuel.
A synergistic photothermal and photocatalytic membrane for efficient solar-driven contaminated water treatment
Authors: Ding Yang , Feng Kai , He Panpan , Liu Ning , Hao Liang , Gong Jiang , Niu Ran , Qu Jinping
Published: September 2021

A synergistic photothermal and photocatalytic membrane is constructed by facilely dip-coating an MXene and graphitic carbon nitride on cotton cloth for solar evaporation and degradation of organic pollutants in source water at the same time.
Copper confined in vesicle-like BCN cavities promotes electrochemical reduction of nitrate to ammonia in water
Authors: Zhao Xue , Hu Guangzhi , Tan Fang , Zhang Shusheng , Wang Xinzhong , Hu Xun , Kuklin Artem V. , Baryshnikov Glib V. , Ågren Hans , Zhou Xiaohai , Zhang Haibo
Published: September 2021

Cu confined in vesicle-like BCN cavities promotes electrochemical reduction of nitrate to ammonia in water.
Revisiting the MIL-101 metal–organic framework: design, synthesis, modifications, advances, and recent applications
Authors: Zorainy Mahmoud Y. , Gar Alalm Mohamed , Kaliaguine Serge , Boffito Daria C.
Published: September 2021

Synthesis of the MIL-101 framework has been attempted from different trivalent metal ions, rather than Cr, like: Fe, Al, V, Ti, Sc, and Mn. In addition, the amino-functionalized form has been successfully reported for some of them.
Development of the accurate localization of partial discharges in medium‐voltage XLPE cables based on pulse reconstruction
Authors: Yang Saike , Zhao Kun , Wang Li , Li Hongjie , Zhang Lin , Lv Qishen
Published: September 2021

A method of reconstructing the original partial discharge (PD) signal to improve the accuracy of PD localization in cross‐linked polyethylene (XLPE) cables is presented here. XLPE cables, extremely sensitive to PDs, are the most popular underground cables in urban grids. The conventional PD localization methods, based on evaluation of the arrival times of PD pulses in the time domain, are negatively affected by the dispersion and attenuation of PD signals propagating in the power cable. A method for the accurate localization of PDs realized through inverse frequency domain modelling (IFDM) is presented here. The method, eliminating the systematic localization error caused by the dispersion and attenuation, significantly improves the localization accuracy. The locations of the PD are identified by comparing peak values of the initial PD signals reconstructed from different extracted pulses. A method for evaluating the propagation constant of the cable is also presented. The efficiency of the accurate localization method was verified by laboratory experiments. Besides, the inherent limitations of the conventional PD localization method for longer cable tests are discussed. The inevitable location error in the conventional methods does not exist in the new method.
Multi‐stage stochastic wind‐thermal generation expansion planning with probabilistic reliability criteria
Authors: Wang Qi , Luo Xianjue , Ma Honglian , Gong Naiwei
Published: September 2021

Due to the growing proportion of uncertain and fluctuating renewable energy sources in the power system, reasonable generation expansion considering the uncertainties is desperately needed. This paper proposes a novel three‐stage wind‐thermal generation expansion planning model based on representative day unit commitment that incorporates the uncertainty of wind power and load and the probabilistic reliability criteria. The probabilistic reliability criteria are considered by simulating random outage events of thermal units using a robust approach. The consequent robust reliability model is reformulated as mixed‐integer linear programming models and integrated into the multi‐stage generation expansion planning model. A decomposed strategy based on the Benders decomposition is adopted to tackle with the large‐scale original model. Case studies are performed on both the revised IEEE 14‐bus and IEEE 118‐bus test systems to validate the effectiveness of proposed model and method. Numerical results show that the proposed generation planning method balances the economy and reliability of the system.
Experimental and molecular level analysis of natural ester delaying degradation of cellulose insulation polymer
Authors: Hao Jian , Ye Wenyu , Gao Chenyu , Zhu Mengzhao , Yang Lijun , Liao Ruijin
Published: September 2021

Developing green insulation materials has become an important direction for future research. As a new environmental insulation liquid, natural ester can effectively delay cellulose insulation polymer ageing. Mastering the mechanism of natural ester delaying the cellulose ageing could promote its application in power transformers. In this study, based on the accelerated thermal ageing of pressboard immersed in natural ester and 25# mineral oil at 120°C for 221 days, the thermal ageing rate and the levelling off degree of polymerisation (LODP) for two kinds of oil‐impregnated pressboards were compared. The molecular level mechanism of natural ester delaying cellulose degradation and keeping higher LODP value was proposed using molecular dynamics simulation. At the early stage of thermal ageing, cellulose with a higher degree of polymerisation (DP) can form many hydrogen bonds with hydronium ions, and their binding energy is stronger, which can accelerate the acid hydrolysis of cellulose, causing the DP of pressboard immersed in natural ester and mineral oil to decrease rapidly. With the breaking of the cellulose molecular chain, the number of hydrogen bonds and binding energy between cellulose and hydronium ions becomes smaller and the thermal ageing rate decreases gradually. At the end stage of ageing, it is difficult for the hydronium ions to enter the crystalline cellulose, acid hydrolysis of crystalline cellulose is hard to conduct, leading to the occurrence of the LODP phenomenon. The degradation rate of cellulose in natural ester is only 50% of that in mineral oil. The cellulose LODP value in natural ester is over 200 larger than that in mineral oil. Compared with the mineral oil‐cellulose system, natural ester can form hydrogen bonds with hydronium ions and lead to fewer hydronium ions in cellulose, fewer hydrogen bonds and smaller binding energy between cellulose and hydronium ions, which can reduce the acid hydrolysis reaction of cellulose. This study provides a theoretical explanation for natural esters to delay the ageing of insulation paper.
A novel characterization method for water trees based on the transmission characteristics of complementary split ring resonators
Authors: Xiao Mi , Wang Xuguang , Ma Haoran , Zhang Wei
Published: September 2021

In order to achieve rapid and simple non‐destructive testing of water trees in materials, a novel water tree characterisation method based on the complementary split ring resonators (CSRR) was proposed. The characteristics of circular CSRR and rectangular CSRR were analysed in high‐frequency electromagnetic simulation software. The resonant frequency of CSRR was found to be correlated to the dielectric constant of the materials. In addition, the lumped equivalent circuit parameters of CSRRs were also calculated and simulated. The results of electromagnetic simulations and circuit simulations achieved good consistency. In the experimental part, sensors based on the two kinds of CSRRs were fabricated and were used to detect the water tree defects in low‐density polyethylene samples. The experiment results showed that the method of using CSRR sensors to detect water tree is feasible.
Inductive power transfer system with constant current and constant voltage outputs for battery charging based on double‐channel T‐circuit
Authors: Wu Yong , Yang Bin , Chen Yonghong , Chen Yang , Mai Ruikun
Published: September 2021

To ensure the safety and effectiveness of charging a battery, constant current and constant voltage (CC‐CV) charging is widely used in inductive power transfer (IPT) systems. A double‐channel T‐circuit (DT) is proposed to obtain CC output or CV output by selecting different work modes with a simple feedback control for various power demands. With the merit of the proposed circuit, fewer components are employed compared to previous work with zero phase angle (ZPA) of inverter in the whole charging process. Besides, an IPT system using DT cascaded with LCC‐S (DTLS) is proposed to improve design freedom of the charge current and charge voltage with the constraints of the magnetic coupler (MC) parameters for CC‐CV charging. Finally, a prototype with 60 V/2 A output was built to verify the theoretical analysis. The experimental results show that the fluctuation of the charging current is less than 2% in CC mode, and that of charging voltage in CV mode is within 4% with the maximum efficiency up to 93.36% during the whole charging process.
Channel state information acquisition method of internet of things based on deep learning
Authors: Zhang Chen
Published: September 2021

As one of the key technologies of Internet of things (IoT), the accurate and efficient acquisition of CSI is an important part to support the high quality communication of IOT system. However, the current IOT system is massive and complex, and the traditional CSI acquisition method is difficult to meet its efficient information communication. To solve this problem, this paper proposes an improved CSI acquisition method based on bidirectional convolutional long and short‐term memory networks (Bidirectional Convolutional Long Short‐Term Memory, Bi‐ConvLSTM) and attention mechanism. This method unifies the Bi‐ConvLSTM‐Attention network module to improve the encoder and decoder of the CSI‐Net network model. Among them, the Bi‐ConvLSTM module is mainly used to learn the time correlation between channel matrices. The attention mechanism module is used to calculate the soft probability distribution, so that the Bi‐ConvLSTM network has the function of automatic weighting, thereby further improving the characterization ability of characteristic information. In the last part of the thesis, the proposed method is simulated and verified. Experimental results show that the proposed method exhibits excellent network performance in both single‐user and multi‐user massive MIMO system scenarios. Compared with the comparison method, the bit error rate performance and system capacity are improved by about 0.3–6 dB and 1.3–3.7 bps/Hz in the multi‐user complex scene.
A structured coagulation-fragmentation equation in the space of radon measures: Unifying discrete and continuous models
Authors: Ackleh Azmy S. , Lyons Rainey , Saintier Nicolas
Published: September 2021

We present a structured coagulation-fragmentation model which describes the population dynamics of oceanic phytoplankton. This model is formulated on the space of Radon measures equipped with the bounded Lipschitz norm and unifies the study of the discrete and continuous coagulation-fragmentation models. We prove that the model is well-posed and show it can reduce down to the classic discrete and continuous coagulation-fragmentation models. To understand the interplay between the physical processes of coagulation and fragmentation and the biological processes of growth, reproduction, and death, we establish a regularity result for the solutions and use it to show that stationary solutions are absolutely continuous under some conditions on model parameters. We develop a semi-discrete approximation scheme which conserves mass and prove its convergence to the unique weak solution. We then use the scheme to perform numerical simulations for the model.
Increased corn oil intake during an allergy sensitization period aggravates food allergy severity after oral allergen exposure
Authors: Maeta Akihiro , Katahira Risako , Takahashi Kyoko
Published: September 2021

Egg white (EW) allergy model mice underwent 15-day oral immunotherapy (OIT) using diets with different corn-oil content and 1% EW. After OIT, mortality following an oral food challenge in OIT groups was approximately 90%. However, in previous studies, mortality was 0%. This phenomenon is to be associated with increased corn-oil intake during allergy sensitization and allergen exposure for 2 weeks.
Enterococcus faecaliscolonizes and forms persistent biofilm microcolonies on undamaged endothelial surfaces in a rabbit endovascular infection model
Authors: Barnes Aaron M T , Frank Kristi L , Dale Jennifer L , Manias Dawn A , Powers Jennifer L , Dunny Gary M
Published: September 2021

Infectious endocarditis (IE) is an uncommon disease with significant morbidity and mortality. The pathogenesis of IE has historically been described as a cascade of host-specific events beginning with endothelial damage and thrombus formation and followed by bacterial colonization of the nascent thrombus. Enterococcus faecalis is a Gram-positive commensal bacterial member of the gastrointestinal tract microbiota in most terrestrial animals and a leading cause of opportunistic biofilm-associated infections, including endocarditis. Here, we provide evidence that E. faecalis can colonize the endocardial surface without pre-existing damage and in the absence of thrombus formation in a rabbit endovascular infection model. Using previously described light and scanning electron microscopy techniques, we show that inoculation of a well-characterized E. faecalis lab strain in the marginal ear vein of New Zealand White rabbits resulted in rapid colonization of the endocardium throughout the heart within 4 days of administration. Unexpectedly, ultrastructural imaging revealed that the microcolonies were firmly attached directly to the endocardium in areas without morphological evidence of gross tissue damage. Further, the attached bacterial aggregates were not associated with significant cellular components of coagulation or host extracellular matrix damage repair (i.e. platelets). These results suggest that the canonical model of mechanical surface damage as a prerequisite for bacterial attachment to host sub-endothelial components is not required. Furthermore, these findings are consistent with a model of initial establishment of stable, endocarditis-associated E. faecalis biofilm microcolonies that may provide a reservoir for the eventual valvular infection characteristic of clinical endocarditis. The similarities between the E. faecalis colonization and biofilm morphologies seen in this rabbit endovascular infection model and our previously published murine gastrointestinal colonization model indicate that biofilm production and common host cell attachment factors are conserved in disparate mammalian hosts under both commensal and pathogenic contexts.
Intermittent fasting and caloric restriction interact with genetics to shape physiological health in mice
Authors: Zhang Guozhu , Deighan Andrew , Raj Anil , Robinson Laura , Donato Hannah J , Garland Gaven , Leland Mackenzie , Martin-McNulty Baby , Kolumam Ganesh A , Riegler Johannes , Freund Adam , Wright Kevin M , Churchill Gary A
Published: September 2021

Dietary interventions can dramatically affect physiological health and organismal lifespan. The degree to which organismal health is improved depends upon genotype and the severity of dietary intervention, but neither the effects of these factors, nor their interaction, have been quantified in an outbred population. Moreover, it is not well understood what physiological changes occur shortly after dietary change and how these may affect the health of an adult population. In this article, we investigated the effect of 6-month exposure of either caloric restriction (CR) or intermittent fasting (IF) on a broad range of physiological traits in 960 1-year old Diversity Outbred mice. We found CR and IF affected distinct aspects of physiology and neither the magnitude nor the direction (beneficial or detrimental) of effects were concordant with the severity of the intervention. In addition to the effects of diet, genetic variation significantly affected 31 of 36 traits (heritabilities ranged from 0.04 to 0.65). We observed significant covariation between many traits that was due to both diet and genetics and quantified these effects with phenotypic and genetic correlations. We genetically mapped 16 diet-independent and 2 diet-dependent significant quantitative trait loci, both of which were associated with cardiac physiology. Collectively, these results demonstrate the degree to which diet and genetics interact to shape the physiological health of adult mice following 6 months of dietary intervention.
Pleiotropy or linkage? Their relative contributions to the genetic correlation of quantitative traits and detection by multitrait GWA studies
Authors: Chebib Jobran , Guillaume Frédéric
Published: September 2021

Genetic correlations between traits may cause correlated responses to selection. Previous models described the conditions under which genetic correlations are expected to be maintained. Selection, mutation, and migration are all proposed to affect genetic correlations, regardless of whether the underlying genetic architecture consists of pleiotropic or tightly linked loci affecting the traits. Here, we investigate the conditions under which pleiotropy and linkage have different effects on the genetic correlations between traits by explicitly modeling multiple genetic architectures to look at the effects of selection strength, degree of correlational selection, mutation rate, mutational variance, recombination rate, and migration rate. We show that at mutation-selection(-migration) balance, mutation rates differentially affect the equilibrium levels of genetic correlation when architectures are composed of pairs of physically linked loci compared to architectures of pleiotropic loci. Even when there is perfect linkage (no recombination within pairs of linked loci), a lower genetic correlation is maintained than with pleiotropy, with a lower mutation rate leading to a larger decrease. These results imply that the detection of causal loci in multitrait association studies will be affected by the type of underlying architectures, whereby pleiotropic variants are more likely to be underlying multiple detected associations. We also confirm that tighter linkage between nonpleiotropic causal loci maintains higher genetic correlations at the traits and leads to a greater proportion of false positives in association analyses.
The Effects of Aging on Male Mouse Pancreatic β-Cell Function Involve Multiple Events in the Regulation of Secretion: Influence of Insulin Sensitivity
Authors: Tudurí Eva , Soriano Sergi , Almagro Lucía , García-Heredia Anabel , Rafacho Alex , Alonso-Magdalena Paloma , Nadal Ángel , Quesada Ivan
Published: September 2021

Aging is associated with a decline in peripheral insulin sensitivity and an increased risk of impaired glucose tolerance and type 2 diabetes. During conditions of reduced insulin sensitivity, pancreatic β cells undergo adaptive responses to increase insulin secretion and maintain euglycemia. However, the existence and nature of β-cell adaptations and/or alterations during aging are still a matter of debate. In this study, we investigated the effects of aging on β-cell function from control (3-month-old) and aged (20-month-old) mice. Aged animals were further categorized into 2 groups: high insulin sensitive (aged-HIS) and low insulin sensitive (aged-LIS). Aged-LIS mice were hyperinsulinemic, glucose intolerant, and displayed impaired glucose-stimulated insulin and C-peptide secretion, whereas aged-HIS animals showed characteristics in glucose homeostasis similar to controls. In isolated β cells, we observed that glucose-induced inhibition of KATP channel activity was reduced with aging, particularly in the aged-LIS group. Glucose-induced islet NAD(P)H production was decreased in aged mice, suggesting impaired mitochondrial function. In contrast, voltage-gated Ca2+ currents were higher in aged-LIS β cells, and pancreatic islets of both aged groups displayed increased glucose-induced Ca2+ signaling and augmented insulin secretion compared with controls. Morphological analysis of pancreas sections also revealed augmented β-cell mass with aging, especially in the aged-LIS group, as well as ultrastructural β-cell changes. Altogether, these findings indicate that aged mouse β cells compensate for the aging-induced alterations in the stimulus-secretion coupling, particularly by adjusting their Ca2+ influx to ensure insulin secretion. These results also suggest that decreased peripheral insulin sensitivity exacerbates the effects of aging on β cells.
Vulcan: Improved long-read mapping and structural variant calling via dual-mode alignment
Authors: Fu Yilei , Mahmoud Medhat , Muraliraman Viginesh Vaibhav , Sedlazeck Fritz J , Treangen Todd J
Published: September 2021

Background

Long-read sequencing has enabled unprecedented surveys of structural variation across the entire human genome. To maximize the potential of long-read sequencing in this context, novel mapping methods have emerged that have primarily focused on either speed or accuracy. Various heuristics and scoring schemas have been implemented in widely used read mappers (minimap2 and NGMLR) to optimize for speed or accuracy, which have variable performance across different genomic regions and for specific structural variants. Our hypothesis is that constraining read mapping to the use of a single gap penalty across distinct mutational hot spots reduces read alignment accuracy and impedes structural variant detection.

Findings

We tested our hypothesis by implementing a read-mapping pipeline called Vulcan that uses two distinct gap penalty modes, which we refer to as dual-mode alignment. The high-level idea is that Vulcan leverages the computed normalized edit distance of the mapped reads via minimap2 to identify poorly aligned reads and realigns them using the more accurate yet computationally more expensive long-read mapper (NGMLR). In support of our hypothesis, we show that Vulcan improves the alignments for Oxford Nanopore Technology long reads for both simulated and real datasets. These improvements, in turn, lead to improved accuracy for structural variant calling performance on human genome datasets compared to either of the read-mapping methods alone.

Conclusions

Vulcan is the first long-read mapping framework that combines two distinct gap penalty modes for improved structural variant recall and precision. Vulcan is open-source and available under the MIT License at https://gitlab.com/treangenlab/vulcan.
The Pediatric Inflammatory Bowel Disease Medical Home: A Proposed Model
Authors: Michel Hilary K , Boyle Brendan , David Jennie , Donegan Amy , Drobnic Barb , Kren Courtney , Maltz Ross M , McKillop Hannah N , McNicol Megan , Oates Melanie , Dotson Jennifer L
Published: September 2021

Care for patients with inflammatory bowel disease (IBD) can be complex and costly. Care delivery models to address these challenges and improve care quality are essential. The patient-centered medical home (PCMH), which was developed in the primary care setting, has recently been applied successfully to the adult IBD population. Following the tenets of the PCMH, this specialty medical home (SMH) emphasizes team-based care that is accessible, comprehensive, patient/family-centered, coordinated, compassionate, and continuous and has demonstrated improved patient outcomes. Children and young adults with IBD have equally complex care needs, with additional challenges not faced by the adult population such as growth, physical and psychosocial development, and transition of care from pediatric to adult providers. Thus, we advocate that the components of the PCMH are equally—if not more—important in caring for the pediatric patient population. In this article, we review what is known about the application of the PCMH model in adult IBD care, describe care delivery within the Center for Pediatric and Adolescent IBD at Nationwide Children’s Hospital as an example of a pediatric IBD medical home, and propose a research agenda to further the development and dissemination of comprehensive care delivery for children and adolescents with IBD.
A Dynamic Dyadic Systems Approach to Interpersonal Communication
Authors: Solomon Denise Haunani , Brinberg Miriam , Bodie Graham D , Jones Susanne , Ram Nilam
Published: September 2021

This article articulates conceptual and methodological strategies for studying the dynamic structure of dyadic interaction revealed by the turn-to-turn exchange of messages between partners. Using dyadic time series data that capture partners’ back-and-forth contributions to conversations, dynamic dyadic systems analysis illuminates how individuals act and react to each other as they jointly construct conversations. Five layers of inquiry are offered, each of which yields theoretically relevant information: (a) identifying the individual moves and dyadic spaces that set the stage for dyadic interaction; (b) summarizing conversational units and sequences; (c) examining between-dyad differences in overall conversational structure; (d) describing the temporal evolution of conversational units and sequences; and (e) mapping within-dyad dynamics of conversations and between-dyad differences in those dynamics. Each layer of analysis is illustrated using examples from research on supportive conversations, and the application of dynamic dyadic systems analysis to a range of interpersonal communication phenomena is discussed.
Temporal Trends of Infective Endocarditis in North America From 2000 to 2017—A Systematic Review
Authors: Talha Khawaja M , Dayer Mark J , Thornhill Martin H , Tariq Wajeeha , Arshad Verda , Tleyjeh Imad M , Bailey Kent R , Palraj Raj , Anavekar Nandan S , Rizwan Sohail M , DeSimone Daniel C , Baddour Larry M
Published: September 2021

Background

The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America.

Methods

A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included.

Results

Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%.

Conclusions

The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.
Harnessing the Potential of Multiomics Studies for Precision Medicine in Infectious Disease
Authors: Ward Rebecca A , Aghaeepour Nima , Bhattacharyya Roby P , Clish Clary B , Gaudillière Brice , Hacohen Nir , Mansour Michael K , Mudd Philip A , Pasupneti Shravani , Presti Rachel M , Rhee Eugene P , Sen Pritha , Spec Andrej , Tam Jenny M , Villani Alexandra-Chloé , Woolley Ann E , Hsu Joe L , Vyas Jatin M
Published: September 2021

The field of infectious diseases currently takes a reactive approach and treats infections as they present in patients. Although certain populations are known to be at greater risk of developing infection (eg, immunocompromised), we lack a systems approach to define the true risk of future infection for a patient. Guided by impressive gains in “omics” technologies, future strategies to infectious diseases should take a precision approach to infection through identification of patients at intermediate and high-risk of infection and deploy targeted preventative measures (ie, prophylaxis). The advances of high-throughput immune profiling by multiomics approaches (ie, transcriptomics, epigenomics, metabolomics, proteomics) hold the promise to identify patients at increased risk of infection and enable risk-stratifying approaches to be applied in the clinic. Integration of patient-specific data using machine learning improves the effectiveness of prediction, providing the necessary technologies needed to propel the field of infectious diseases medicine into the era of personalized medicine.
Performance of Self-Collected Anterior Nasal Swabs and Saliva Specimens for Detection of SARS-CoV-2 During Symptomatic and Asymptomatic Periods
Authors: Grijalva Carlos G , Rolfes Melissa , Zhu Yuwei , Chappell James , Halasa Natasha , Kim Ahra , Reed Carrie , Fry Alicia , Talbot H Keipp
Published: September 2021

Background

Anterior nasal swabs (ANS) are established specimen collection methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detection. While saliva (SA) specimens provide an alternative, few studies have comprehensively characterized the performance of SA specimens in longitudinal studies.

Methods

We compared SARS-CoV-2 detections between paired self-collected ANS and SA specimens from a household transmission study. Participants recorded symptoms and paired ANS and SA specimens daily for 14 days. Specimens were tested using RT-PCR. We calculated the proportion of detections identified by each specimen type among the detections from both types combined. We computed percent agreement and Kappa statistics to assess concordance in detections. We also computed estimates stratified by presence of symptoms and examined the influence of traditional and inactivating transport media on the performance of ANS.

Results

We examined 2535 self-collected paired specimens from 216 participants. Among 1238 (49%) paired specimens with detections by either specimen type, ANS identified 77.1% (954; 95% CI, 74.6% to 79.3%) and SA 81.9% (1014; 95% CI, 79.7% to 84.0%), with a difference of 4.9% (95% CI, 1.4% to 8.5%). Overall agreement was 80.0%, and Kappa was 0.6 (95% CI, 0.5 to 0.6). Nevertheless, the difference in the proportion of detections identified by ANS and SA using traditional and inactivating transport media was 32.5% (95% CI, 26.8% to 38.0%) and –9.5% (95% CI, −13.7% to –5.2%), respectively. Among participants who remained asymptomatic, the difference in detections between SA and ANS was 51.2% (95% CI, 31.8% to 66.0%) and 26.1% (95% CI, 0% to 48.5%) using traditional and inactivating media, respectively.

Conclusions

Self-collected saliva specimens provide a noninvasive alternative to nasal swabs, especially to those collected in traditional transport media, for longitudinal field studies that aim to detect both symptomatic and asymptomatic SARS-CoV-2 infections.