bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+ Tissue-resident Memory T Cells Expand and Are a Major Source of Mucosal Tumour Necrosis Factor α in Active Crohn’s Disease
Authors: Bishu Shrinivas , El Zaatari Mohammed , Hayashi Atsushi , Hou Guoqing , Bowers Nicole , Kinnucan Jami , Manoogian Beth , Muza-Moons Michelle , Zhang Min , Grasberger Helmut , Bourque Charlie , Zou Weiping , Higgins Peter D R , Spence Jason R , Stidham Ryan W , Kamada Nobuhiko , Kao John Y 
Published: January 2019

Abstract

Background and Aims
Tumour necrosis factor [TNF]α- and IL-17A-producing T cells are implicated in Crohn’s disease [CD]. Tissue-resident memory T [TRM] cells are tissue-restricted T cells that are regulated by PR zinc finger domain 1 [PRDM1], which has been implicated in pathogenic Th17 cell responses. TRM cells provide host defence but their role in CD is unknown. We thus examined CD4+ TRM cells in CD.

Methods
Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterise CD4+ TRM cells.

Results
CD4+ TRM cells are the most abundant memory T cell population and are the major T cell source of mucosal TNFα in CD. CD4+ TRM cells are expanded in CD and more avidly produce IL-17A and TNFα relative to control cells. There was a unique population of TNFα+IL-17A+ CD4+ TRM cells in CD which are largely absent in controls. PRDM1 was highly expressed by CD4+ TRM cells but not by other effector T cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4+ TRM cells

Conclusions
CD4+ TRM cells are expanded in CD and are a major source of TNFα, suggesting that they are important in CD. PRDM1 is expressed by TRM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4+ TRM cells over the disease course.
Grandparents’ Financial Contributions to Grandchildren in Rural China: The Role of Remittances, Household Structure, and Patrilineal Culture
Authors: Silverstein Merril , Zhang Wencheng 
Published: January 2019

AbstractObjectivesThis investigation examined predictors of monetary transfers made by grandparents for the benefit of their grandchildren in rural China. Predictors included family factors related to financial supply (remittances received from the parents of grandchildren), household demand (living in a skipped-generation household), and patrilineal culture (targeting sons and grandsons).MethodThe 2015 wave of the Longitudinal Study of Older Adults in Anhui Province was used to study financial transfers made by 831 grandparents to grandchildren in the families of 1,633 parents. Two-part random-effects regression was used to predict whether a transfer was made and the value of transfers, given that one occurred.ResultsGrandparents provided higher value transfers to grandchildren whose parents provided greater remittances and with whom they coresided in skipped-generation households. The likelihood of making a transfer fully followed the male lineage, and was greatest to grandson-only families in which parents were first-born sons.DiscussionResults show that economic, household, and cultural factors are independently associated with the largesse of grandparents. We conclude that grandparents’ economic contributions to grandchildren in rural China are shaped by family demands in a highly mobile society, intergenerational interdependence, and a persistent patrilineal gender system that reaches to the level of grandchildren.
A federated EHR network data completeness tracking system
Authors: Estiri Hossein , Klann Jeffrey G , Weiler Sarah R , Alema-Mensah Ernest , Joseph Applegate R , Lozinski Galina , Patibandla Nandan , Wei Kun , Adams William G , Natter Marc D , Ofili Elizabeth O , Ostasiewski Brian , Quarshie Alexander , Rosenthal Gary E , Bernstam Elmer V , Mandl Kenneth D , Murphy Shawn N 
Published: January 2019

Abstract

Objective
The study sought to design, pilot, and evaluate a federated data completeness tracking system (CTX) for assessing completeness in research data extracted from electronic health record data across the Accessible Research Commons for Health (ARCH) Clinical Data Research Network.

Materials and Methods
The CTX applies a systems-based approach to design workflow and technology for assessing completeness across distributed electronic health record data repositories participating in a queryable, federated network. The CTX invokes 2 positive feedback loops that utilize open source tools (DQe-c and Vue) to integrate technology and human actors in a system geared for increasing capacity and taking action. A pilot implementation of the system involved 6 ARCH partner sites between January 2017 and May 2018.

Results
The ARCH CTX has enabled the network to monitor and, if needed, adjust its data management processes to maintain complete datasets for secondary use. The system allows the network and its partner sites to profile data completeness both at the network and partner site levels. Interactive visualizations presenting the current state of completeness in the context of the entire network as well as changes in completeness across time were valued among the CTX user base.

Discussion
Distributed clinical data networks are complex systems. Top-down approaches that solely rely on technology to report data completeness may be necessary but not sufficient for improving completeness (and quality) of data in large-scale clinical data networks. Improving and maintaining complete (high-quality) data in such complex environments entails sociotechnical systems that exploit technology and empower human actors to engage in the process of high-quality data curating.

Conclusions
The CTX has increased the network’s capacity to rapidly identify data completeness issues and empowered ARCH partner sites to get involved in improving the completeness of respective data in their repositories.
Misidentification of Burkholderia pseudomallei and Other Burkholderia Species From Pediatric Infections in Mexico
Authors: Meza-Radilla Georgina , Mendez-Canarios Ausel , Xicohtencatl-Cortes Juan , Escobedo-Guerra Marcos R , Torres Alfredo G , Ibarra J Antonio , Estrada-de los Santos Paulina 
Published: January 2019

Abstract
Burkholderia pseudomallei and Burkholderia cepacia complex are poorly studied in Mexico. The genotypic analysis of 38 strains isolated from children with pneumonia were identified and showed that both Burkholderia groups were present in patients. From our results, it is plausible to suggest that new species are among the analyzed strains.
Net charge of antibody complementarity-determining regions is a key predictor of specificity
Authors: Rabia Lilia A , Zhang Yulei , Ludwig Seth D , Julian Mark C , Tessier Peter M 
Published: January 2019

Abstract
Specificity is one of the most important and complex properties that is central to both natural antibody function and therapeutic antibody efficacy. However, it has proven extremely challenging to define robust guidelines for predicting antibody specificity. Here we evaluated the physicochemical determinants of antibody specificity for multiple panels of antibodies, including &gt;100 clinical-stage antibodies. Surprisingly, we find that the theoretical net charge of the complementarity-determining regions (CDRs) is a strong predictor of antibody specificity. Antibodies with positively charged CDRs have a much higher risk of low specificity than antibodies with negatively charged CDRs. Moreover, the charge of the entire set of six CDRs is a much better predictor of antibody specificity than the charge of individual CDRs, variable domains (VH or VL) or the entire variable fragment (Fv). The best indicators of antibody specificity in terms of CDR amino acid composition are reduced levels of arginine and lysine and increased levels of aspartic and glutamic acid. Interestingly, clinical-stage antibodies with negatively charged CDRs also have a lower risk for poor biophysical properties in general, including a reduced risk for high levels of self-association. These findings provide powerful guidelines for predicting antibody specificity and for identifying safe and potent antibody therapeutics.
Effect of ceftiofur cessation and substitution with lincomycin-spectinomycin on extended-spectrum-beta-lactamase/AmpC genes and multidrug resistance in E. coli from a Canadian broiler production pyramid
Authors: Verrette L. , Fairbrother J. M. , Boulianne M. 
Published: January 2019

AbstractCeftiofur, a cephalosporin antimicrobial, was used systematically in Canadian hatcheries for many years to prevent early mortality in chicks leading to a high prevalence of cephalosporin resistance in Escherichia coli in chickens. Preventive use of ceftiofur in hatcheries ceased in 2014. We examined the effect of ceftiofur cessation and replacement with lincomycin-spectinomycin at the hatchery on the proportion of E. coli positive for extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase related genes, and on the multidrug resistance profiles of ESBL/AmpC positive E. coli in broilers and their associated breeders, at one year post-cessation. For indicator E. coli from non-enriched media, a significant decrease post-cessation in the proportion of samples harboring E. coli isolates positive for blaCMY-2 and/or blaCTX-M was observed. In contrast, following enrichment in medium containing ceftriaxone (1mg/L) to facilitate recovery of ESBL/AmpC β-lactamase producing E. coli colonies, both pre- and post-cessation, 99% of the samples harbored E. coli positive for blaCMY-2 or blaCTX-M. Flocks receiving lincomycin-spectinomycin after cessation of ceftiofur showed a significantly greater non-susceptibility to aminoglycoside, folate inhibitor, phenicol, tetracycline and possible extensively drug resistant E. coli compared to those receiving ceftiofur or no antimicrobial at hatchery. This study clearly demonstrates an initial decrease in ESBL/AmpC positive E. coli following the cessation of ceftiofur in hatchery but an increase in multidrug resistant E. coli following replacement with lincomycin-spectinomycin.ImportanceAntimicrobial resistance is a global problem. The antimicrobial ceftiofur has been used worldwide for disease prevention in poultry production resulting in a greatly increased resistance to this antimicrobial important in poultry and human medicine. Our study examines the impact of ceftiofur cessation and its replacement with the antimicrobial combination lincomycin-spectinomycin, a common practice in the industry. Our study demonstrated a decrease in ceftiofur resistance after the cessation of its use, although the resistance genes remain ubiquitous in all phases of poultry production, showing that poultry remains a reservoir for ceftiofur resistance and requiring continued vigilance. We also observed a decrease in multidrug resistance after cessation of ceftiofur although the contrary finding following use of lincomycin-spectinomycin indicates that the use of these antimicrobials should be questioned. Reduced resistance to ceftiofur in poultry may translate to better treatment efficacy, decreased morbidity, mortality, duration and cost of hospitalization in humans.
Fear contagion in zebrafish: a behaviour affected by familiarity
Authors: Silva Priscila Fernandes , de Leaniz Carlos Garcia , Luchiari Ana Carolina 
Published: January 2019

AbstractEmotional contagion has recently been described in fish but whether it is affected by familiarity is not known. We tested whether the sight of a distressed conspecific elicited fear in zebrafish, and whether this was modulated by familiarity. Groups of six zebrafish were housed together in the same tanks for 7 days to create familiar conditions. The behaviour of individual fish was then recorded in paired tanks within sight of either a familiar or an unfamiliar individual, before and after distilled water or an alarm substance was added to the demonstrator, but not to the observer. As expected, addition of distilled water did not elicit any behavioural change in either the demonstrator or the observer. However, addition of an alarm cue triggered anti-predatory behaviours in the demonstrator which caused the expression of anti-predatory behaviours in the observer, suggesting the existence of fear contagion. Furthermore, the extent of fear contagion was affected by familiarity, and observers were more active, swam closer to the bottom and further away from the demonstrator when they watched a distressed familiar neighbour than when they watched an unfamiliar fish. Our results have implications for fish welfare because they show that fish can become stressed by simply watching others become stressed. They also have implications for experimental design because fish housed in separate tanks cannot be assumed to be statistically independent if they can eavesdrop on their neighbours.
Progressive domain segregation in early embryonic development and underlying correlation to genetic and epigenetic changes
Authors: Quan Hui , Tian Hao , Liu Sirui , Xue Yue , Zhang Yu , Xie Wei , Gao Yi Qin 
Published: January 2019

ABSTRACTChromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming and the corresponding sequence dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests and prairies, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which notable domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. Chromatin of ectoderm shows the weakest and endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges in further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest DNA sequence as a possible driving force for the establishment of chromatin 3D structures which affect profoundly the expression profile. Other possible factors correlated with/influencing chromatin structures, including temperature, germ layers, and cell cycle, were discussed for an understanding of concerted chromatin structure and epigenetic changes in development.
The effects of aging on neural signatures of temporal regularity processing in sounds
Authors: Herrmann Björn , Buckland Chad , Johnsrude Ingrid S. 
Published: January 2019

AbstractSensitivity to temporal regularity (e.g., amplitude modulation) is crucial for speech perception. Degradation of the auditory periphery due to aging and hearing loss may lead to an increased response gain in auditory cortex, with potential consequences for the processing of temporal regularities. We used electroencephalography recorded from younger (18–33 years) and older (55–80 years) adults to investigate how aging affects neural gain and the neural sensitivity to amplitude modulation in sounds. Aging was associated with reduced adaptation in auditory cortex, suggesting an age-related gain increase. Consistently, neural synchronization in auditory cortex to a 4-Hz amplitude modulation of a narrow-band noise was enhanced in ~30% of older individuals. Despite enhanced responsivity in auditory cortex, sustained neural activity (likely involving auditory and higher-order brain regions) in response to amplitude modulation was absent in older people. Hence, aging may lead to an over-responsivity to amplitude modulation in auditory cortex, but to a diminished regularity representation in higher-order areas.
Induction of an alternative 5’ leader enhances translation of Inpp5e and resistance to oncolytic virus infection
Authors: Hoang Huy-Dung , Graber Tyson E. , Jia Jian-Jun , Vaidya Nasana , Gilchrist Victoria , Li Wencheng , Gkogkas Christos G. , Jaramillo Maritza , Jafarnejad Seyed Mehdi , Alain Tommy 
Published: January 2019

ABSTRACTResidual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. mRNA translation is an important component of innate immunity, yet the targeted cellular mRNAs remain ill-defined. We characterized the translatome of resistant murine “4T1” breast cancer cells infected with three of the most clinically advanced oncolytic viruses: Herpes Simplex virus 1, Reovirus and Vaccinia virus. Common among all three infections were translationally de-repressed mRNAs involved in ciliary homeostasis including Inpp5e, encoding an inositol 5-phosphatase that modifies lipid second messenger signalling. Translationally repressed in the uninfected condition, viral infection induced expression of an Inpp5e mRNA variant that lacks repressive upstream open reading frames (uORFs) within its 5’ leader and is consequently efficiently translated. Furthermore, we show that INPP5E contributes to antiviral immunity by altering virus attachment. These findings uncover a role for translational control through alternative 5’ leader expression and assign ciliary proteins such as INPP5E to the cellular antiviral response.
Mosquito and primate ecology predict human risk of yellow fever virus spillover in Brazil
Authors: Childs Marissa L. , Nova Nicole , Colvin Justine , Mordecai Erin A. 
Published: January 2019

AbstractMany (re)emerging infectious diseases in humans arise from pathogen spillover from wildlife or livestock, and accurately predicting pathogen spillover is an important public health goal. In the Americas, yellow fever in humans primarily occurs following spillover from non-human primates via mosquitoes. Predicting yellow fever spillover can improve public health responses through vector control and mass vaccination. Here, we develop and test a mechanistic model of pathogen spillover to predict human risk for yellow fever in Brazil. This environmental risk model, based on the ecology of mosquito vectors and non-human primate hosts, distinguished municipality-months with yellow fever spillover from 2001 to 2016 with high accuracy (AUC = 0.72). Incorporating hypothesized cyclical dynamics of infected primates improved accuracy (AUC = 0.79). Using boosted regression trees to identify gaps in the mechanistic model, we found that important predictors include current and one-month lagged environmental risk, vaccine coverage, population density, temperature, and precipitation. More broadly, we show that for a widespread human viral pathogen, the ecological interactions between environment, vectors, reservoir hosts, and humans can predict spillover with surprising accuracy, suggesting the potential to improve preventative action to reduce yellow fever spillover and prevent onward epidemics in humans.
How macroecology affects macroevolution: the interplay between extinction intensity and trait-dependent extinction in brachiopods
Authors: Smits Peter D. 
Published: January 2019

AbstractSelection is the force behind differences in fitness, with extinction being the most extreme example of selection. Modern experiments and observations have shown that average fitness and selection strength can vary over time and space. This begs the question: as average fitness increases, does selection strength increase or decrease? The fossil record illustrates how extinction rates have varied through time, with periods of both rapid and slow species turnover. Using Paleozoic brachiopods as a study system, I developed a model to understand how the average taxon duration (i.e. fitness) varies over time, to estimate trait-based differences in taxon durations (i.e. selection), and to measure the amount of correlation between taxon fitness and selection. I find evidence for when extinction intensity increases, selection strength on geographic range also increases. I also find strong evidence for a non-linear relationship between environmental preference for epicontinental versus open-ocean environments and expected taxon duration, where taxa with intermediate preferences are expected to have greater durations than environmental specialists. Finally, I find that taxa which appear more frequently in epicontinental environments will have a greater expected duration than those taxa which prefer open-ocean environments. My analysis supports the conclusions that as extinction intensity increases and average fitness decreases, as happens during a mass extinction, the trait-associated differences in fitness would increase. In contrast, during periods of low extinction intensity when fitness is greater than average, my model predicts that selection associated with geographic range and environmental preference would decrease and be less than average.
Usiigaci: Instance-aware cell tracking in stain-free phase contrast microscopy enabled by machine learning
Authors: Tsai Hsieh-Fu , Gajda Joanna , Sloan Tyler F.W. , Rares Andrei , Shen Amy Q. 
Published: January 2019

AbstractStain-free, single-cell segmentation and tracking is tantamount to the holy grail of microscopic cell migration analysis. Phase contrast microscopy (PCM) images with cells at high density are notoriously difficult to segment accurately; thus, manual segmentation remains the de facto standard practice. In this work, we introduce Usiigaci, an all-in-one, semi-automated pipeline to segment, track, and visualize cell movement and morphological changes in PCM. Stain-free, instance-aware segmentation is accomplished using a mask regional convolutional neural network (Mask R-CNN). A Trackpy-based cell tracker with a graphical user interface is developed for cell tracking and data verification. The performance of Usiigaci is validated with electrotaxis of NIH/3T3 fibroblasts. Usiigaci provides highly accurate cell movement and morphological information for quantitative cell migration analysis.
The Prrx1 limb enhancer marks an adult population of injury-responsive dermal fibroblasts
Authors: Currie Joshua D. , Grosser Lidia , Murawala Prayag , Schuez Maritta , Michel Martin , Tanaka Elly M. , Sandoval-Guzmán Tatiana 
Published: January 2019

SummaryThe heterogeneous properties of dermal cell populations have been posited to contribute toward fibrotic, imperfect wound healing in mammals. Here we characterize an adult population of dermal fibroblasts that maintain an active Prrx1 enhancer which originally marked mesenchymal limb progenitors. In contrast to their abundance in limb development, postnatal Prrx1 enhancer-positive cells (Prrx1enh+) make up a small subset of adult dermal cells (∼0.2%) and reside mainly within dermal perivascular and hair follicle niches. Lineage tracing of adult Prrx1enh+ cells shows that they remain in their niches and in small number over a long period of time. Upon injury however, Prrx1enh+ cells readily migrate into the wound bed and amplify on average 16-fold beyond their uninjured numbers. Additionally, following wounding dermal Prrx1enh+ cells are found out of their dermal niches and contribute to subcutaneous tissue. Postnatal Prrx1enh+ cells are uniquely injury-responsive despite being a meager minority in the adult skin.