bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymph Nodes Inhibit T-cell Effector Functions Locally by Establishing Acidic Niches
Authors: Wu Hao , Estrella Veronica , Enriquez-Navas Pedro , El-Kenawi Asmaa , Russell Shonagh , Abrahams Dominique , Ibrahim-Hashim Arig , Longo Dario , Reshetnyak Yana , Luddy Kimberly , Damaghi Mehdi , Pillai Smitha Ravindranadhan , Beatty Matthew , Pilon-Thomas Shari , Swietach Pawel , Gillies Robert J. 
Published: July 2019

AbstractLymph nodes are an essential component of the adaptive immune response where antigen-presenting cells are closely housed with their cognate effector cells. Protection of lymph node resident cells from activated immune cells in such close quarters would need to be robust and reversible. Effector functions of T-cells are profoundly and reversibly inhibited by an acidic microenvironment. The underlying mechanisms of this inhibition are unknown, but may relate to glycolysis, which is obligatory for expression of effector functions. Here, we demonstrate that acidification rapidly and potently inhibits monocarboxylate transporter-dependent lactic acid efflux, which dually inhibits glycolysis by end-product accumulation and by reducing cytoplasmic pH. Based on the robustness of these responses, we propose that acid-evoked T-cell inhibition is physiologically important, and that lymph nodes are a natural site for such modulation. Using multiple imaging techniques, we show that paracortical T-zones of lymph nodes are highly acidic. We further show that T-cells can be activated by dendritic cells at low pH, and their effector functions are restored rapidly upon increasing pH. Thus, we describe a novel physiological mechanism whereby activated T-cells are kept in stasis by acidosis whilst resident in lymph nodes.
A database for ITS2 sequences from nematodes
Authors: Workentine Matthew L. , Chen Rebecca , Zhu Shawna , Gavriliuc Stefan , Shaw Nicolette , de Rijke Jill , Redman Elizabeth M. , Avarmenko Russell W. , Wit Janneke , Poissant Jocelyn , Gilleard John S. 
Published: July 2019

SummaryMarker gene surveys have a wide variety of applications in species identification, population genetics, and molecular epidemiology. As these methods expand to new types of organisms and additional markers beyond 16S and 18S rRNA genes, comprehensive databases are a critical requirement for proper analysis of these data. Here we present an ITS2 rDNA database for maker gene surveys of both free-living and parasitic nematode populations and the software used to build the database. This is an important resource for researchers working on nematodes and also provides a tool to create ITS2 databases for any given taxonomy.Availability and ImplementationThe database is available as an interactive web app at https://cooperia.chgi.ucalgary.ca/Nematode_ITS2/. The full database can also be downloaded from zenodo https://doi.org/10.5281/zenodo.3235802, and the open source software used to create the database, markerDB is available at https://github.com/ucvm/markerDB/releases/latest.
Predicting Primary Site of Secondary Liver Cancer with a Neural Estimator of Metastatic Origin (NEMO)
Authors: Schau Geoffrey F. , Burlingame Erik A. , Thibault Guillaume , Anekpuritanang Tauangtham , Wang Ying , Gray Joe W. , Corless Christopher , Chang Young Hwan 
Published: July 2019

AbstractPathologists rely on clinical information, tissue morphology, and sophisticated molecular diagnostics to accurately infer the metastatic origin of secondary liver cancer. In this paper, we introduce a deep learning approach to identify spatially localized regions of cancerous tumor within hematoxylin and eosin stained tissue sections of liver cancer and to generate predictions of the cancer’s metastatic origin. Our approach achieves an accuracy of 90.2% when classifying metastatic origin of whole slide images into three distinct classes, which compares favorably to an established clinical benchmark by three board-certified pathologists whose accuracies ranged from 90.2% to 94.1% on the same prediction task. This approach illustrates the potential impact of deep learning systems to leverage morphological and structural features of H&E stained tissue sections to guide pathological and clinical determination of the metastatic origin of secondary liver cancers.
Critical slowing as a biomarker for seizure susceptibility
Authors: Maturana Matias I. , Meisel Christian , Dell Katrina , Karoly Philippa J. , D’Souza Wendyl , Grayden David B. , Burkitt Anthony N. , Jiruska Premysl , Kudlacek Jan , Hlinka Jaroslav , Cook Mark J. , Kuhlmann Levin , Freestone Dean R. 
Published: July 2019

AbstractThe human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system would suggest that prior to a seizure recorded brain signals may exhibit critical slowing, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we found key signatures of critical slowing prior to seizures. Signals related to a critically slowing process fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing is a reliable indicator that could be used in seizure forecasting algorithms.
Transient uterine hypercontractility causes fetal cerebral oxidative stress and enduring mitochondrial and behavioral abnormalities in adolescent male rat offspring
Authors: Palanisamy Arvind , Giri Tusar , Jiang Jia , Bice Annie , Quirk James D. , Conyers Sara B. , Maloney Susan E. , Raghuraman Nandini , Bauer Adam Q. , Garbow Joel R. , Wozniak David F. 
Published: July 2019

AbstractThe impact of transient ischemic-hypoxemic insults on the developing fetal brain is poorly understood despite evidence suggesting an association with neurodevelopmental disorders such as schizophrenia and autism. To address this, we designed an aberrant uterine hypercontractility paradigm with oxytocin to better assess the consequences of acute, but transient, placental ischemia-hypoxemia in term pregnant rats. Using MRI imaging, we confirmed that oxytocin-induced aberrant uterine hypercontractility significantly compromised uteroplacental perfusion. This was supported by the observation of oxidative stress and increased lactate concentration in the fetal brain. Genes related to oxidative stress pathways were significantly upregulated in male, but not female, offspring 1 h after oxytocin-induced placental ischemia-hypoxemia. Persistent upregulation of select mitochondrial electron transport chain complex proteins in the anterior cingulate cortex of adolescent male offspring suggested that this sex-specific effect was enduring. Functionally, offspring exposed to oxytocin-induced uterine hypercontractility showed male-specific abnormalities in social behavior with associated region-specific changes in gene expression and functional cortical connectivity. Our findings, therefore, indicate that even transient but severe placental ischemia-hypoxemia could be detrimental to the developing brain and point to a possible mitochondrial link between intrauterine asphyxia and neurodevelopmental disorders.
Depression, GABA and age correlate with the plasma levels of inflammatory markers
Authors: Bhandage Amol K. , Cunningham Janet L. , Jin Zhe , Shen Qiujin , Bongiovanni Santiago , Korol Sergiy V. , Syk Mikaela , Kamali-Moghaddam Masood , Ekselius Lisa , Birnir Bryndis 
Published: July 2019

AbstractImmunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined if levels of immunological protein markers altered with depression, age or by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Analysis of plasma samples from patients with major depressive episode and control blood donors (CBD) revealed expression of 67 inflammatory markers. Thirteen of these markers had augmented levels in patients as compared to CBD. and 21 markers correlated with age of the patients, whereas 10 markers correlated with the age of CBD. Interestingly, CST5 and CDCP1 showed the strongest correlation with age in the patients and in the CBD, respectively. IL-18 was the only marker that correlated with the MADRS-S scores of the patients. Neuronal growth factors (NGFs) were significantly enhanced in plasma from the patients and so was the average plasma GABA concentration. GABA modulated release of seven cytokines in CD3+ stimulated peripheral blood mononuclear cells (PBMC) from the patients. The study reveals significant changes in plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.
Detection and identification of bacterialspp.from culture negative surgical site infection patients using molecular tool
Authors: Behera Himanshu Sekhar , Chayani Nirupama , Bal Madhusmita , Pati Sanghamitra , Das Sashibhusan , Khuntia Hemant Kumar , Ranjit Manoranjan 
Published: July 2019

AbstractSurgical site infection (SSI) is the most common post operative infections, that sometimes cause postoperative morbidity, mortality and increase in hospital costs. Managing surgical site infections, with negative culture report in routine diagnosis is a common dilemma in microbiology. The present study was carried out to know the presence and frequencies of various bacteria in wound aspirates/ swabs of some culture negative surgical site infection patients attending a tertiary care hospital of eastern India with molecular methods. Ninety seven (97) patients with post-operative SSI whose wound swabs/ aspirate were negative in the conventional aerobic culture after 48 hrs of incubation were taken for finding the presence and identification of any bacteria in sample with 16S rRNA gene specific broad PCR and submitted to NCBI. Of the 97 patients, 16S rRNA based broad range PCR assay could able to identify the presence of bacterial pathogen in 53(54.63%) cases, out of which 29 isolates were of viable but non-culturable bacteria(VBNC), 07 were of obligatory anaerobes and 13 were of unculturable bacteria, 04 were with polybacterial infections. Some measures should be taken in the microbiology laboratory along with conventional culture, for better patient care such as, culture plates should be allowed to incubate for an additional 3 – 4 days that will allow the growth any fastidious bacteria, anaerobic culture system should be developed along with aerobic system, and molecular diagnosis by 16S broad range PCR should be performed routinely.
Hierarchical non-negative matrix factorization using clinical information for microbial communities
Authors: Abe Ko , Hirayama Masaaki , Ohno Kinji , Shimamura Teppei 
Published: July 2019

AbstractBackgroundThe human microbiome forms very complex communities that consist of hundreds to thousands of different microorganisms that not only affect the host, but also participate in disease processes. Several state-of-the-art methods have been proposed for learning the structure of microbial communities and to investigate the relationship between microorganisms and host environmental factors. However, these methods were mainly designed to model and analyze single microbial communities that do not interact with or depend on other communities. Such methods therefore cannot comprehend the properties between interdependent systems in communities that affect host behavior and disease processes.ResultsWe introduce a novel hierarchical Bayesian framework, called BALSAMICO (BAyesian Latent Semantic Analysis of MIcrobial COmmunities), which uses microbial metagenome data to discover the underlying microbial community structures and the associations between microbiota and their environmental factors. BALSAMICO models mixtures of communities in the framework of nonnegative matrix factorization, taking into account environmental factors. This method first proposes an efficient procedure for estimating parameters. A simulation then evaluates the accuracy of the estimated parameters. Finally, the method is used to analyze clinical data. In this analysis, we successfully detected bacteria related to colorectal cancer. These results show that the method not only accurately estimates the parameters needed to analyze the connections between communities of microbiota and their environments, but also allows for the effective detection of these communities in real-world circumstances.
Neural network and random forest models in protein function prediction
Authors: Hakala Kai , Kaewphan Suwisa , Björne Jari , Mehryary Farrokh , Moen Hans , Tolvanen Martti , Salakoski Tapio , Ginter Filip 
Published: July 2019

AbstractOver the past decade, the demand for automated protein function prediction has increased due to the volume of newly sequenced proteins. In this paper, we address the function prediction task by developing an ensemble system automatically assigning Gene Ontology (GO) terms to the given input protein sequence.We develop an ensemble system which combines the GO predictions made by random forest (RF) and neural network (NN) classifiers. Both RF and NN models rely on features derived from BLAST sequence alignments, taxonomy and protein signature analysis tools. In addition, we report on experiments with a NN model that directly analyzes the amino acid sequence as its sole input, using a convolutional layer. The Swiss-Prot database is used as the training and evaluation data.In the CAFA3 evaluation, which relies on experimental verification of the functional predictions, our submitted ensemble model demonstrates competitive performance ranking among top-10 best-performing systems out of over 100 submitted systems. In this paper, we evaluate and further improve the CAFA3-submitted system. Our machine learning models together with the data pre-processing and feature generation tools are publicly available as an open source software athttps://github.com/TurkuNLP/CAFA3Author summaryUnderstanding the role and function of proteins in biological processes is fundamental for new biological discoveries. Whereas modern sequencing methods have led to a rapid growth of protein databases, the function of these sequences is often unknown and expensive to determine experimentally. This has spurred a lot of interest in predictive modelling of protein functions.We develop a machine learning system for annotating protein sequences with functional definitions selected from a vast set of predefined functions. The approach is based on a combination of neural network and random forest classifiers with features covering structural and taxonomic properties and sequence similarity. The system is thoroughly evaluated on a large set of manually curated functional annotations and shows competitive performance in comparison to other suggested approaches. We also analyze the predictions for different functional annotation and taxonomy categories and measure the importance of different features for the task. This analysis reveals that the system is particularly efficient for bacterial protein sequences.
Sex-dependent and -independent transcriptional changes during haploid phase gametogenesis in the sugar kelpSaccharina latissima
Authors: Pearson Gareth A , Martins Neusa , Madeira Pedro , Serrão Ester A , Bartsch Inka 
Published: July 2019

AbstractIn haplodiplontic lineages, sexual reproduction occurs in haploid parents without meiosis. Although widespread in multicellular lineages such as brown algae (Phaeophyceae), haplodiplontic gametogenesis has been little studied at the molecular level. We addressed this by generating an annotated reference transcriptome for the gametophytic phase of the sugar kelp,Saccharina latissima. Transcriptional profiles of microscopic male and female gametophytes were analysed at four time points during the transition from vegetative growth to gametogenesis. Gametogenic signals resulting from a switch in culture irradiance from red to white light activated a core set of genes in a sex-independent manner, involving rapid activation of ribosome biogenesis, transcription and translation related pathways, with several acting at the post-transcriptional or post-translational level. Additional genes regulating nutrient acquisition and key carbohydrate-energy pathways were also identified. Candidate sex-biased genes under gametogenic conditions had potentially key roles in controlling female- and male-specific gametogenesis. Among these were several sex-biased or - specific E3 ubiquitin-protein ligases that may have important regulatory roles. Females specifically expressed several genes that coordinate gene expression and/or protein degradation, and the synthesis of inositol-containing compounds. Other female-biased genes supported parallels with oogenesis in divergent multicellular lineages, in particular reactive oxygen signalling via an NADPH-oxidase. Males specifically expressed the hypothesised brown algal sex-determining factor. Male-biased expression mainly involved upregulation of genes that control mitotic cell proliferation and spermatogenesis in other systems, as well as multiple flagella-related genes. Our data and results enhance genome-level understanding of gametogenesis in this ecologically and economically important multicellular lineage.
Prevalence of pelagic dependence among coral reef predators across an atoll seascape
Authors: Skinner Christina , Newman Steven P. , Mill Aileen C. , Newton Jason , Polunin Nicholas V. C. 
Published: July 2019

Abstract

Coral reef food webs are complex, vary spatially and remain poorly understood. Certain large predators, notably sharks, are subsidized by pelagic production on outer reef slopes, but how widespread this dependence is across all teleost fishery target species and within atolls is unclear.

North Malé Atoll (Maldives) includes oceanic barrier as well as lagoonal reefs. Nine fishery target predators constituting ca. 55% of the local fishery target species biomass at assumed trophic levels 3–5 were selected for analysis. Data were derived from carbon (δ13C), nitrogen (δ15N) and sulphur (δ34S) stable isotopes from predator white dorsal muscle samples, and primary consumer species representing production source end‐members.

Three‐source Bayesian stable isotope mixing models showed that uptake of pelagic production extends throughout the atoll, with predatory fishes showing equal planktonic reliance between inner and outer edge reefs. Median plankton contribution was 65%–80% for all groupers and 68%–88% for an emperor, a jack and snappers.

Lagoonal and atoll edge predators are equally at risk from anthropogenic and climate‐induced changes, which may impact the linkages they construct, highlighting the need for management plans that transcend the boundaries of this threatened ecosystem.
Associations between gamebird releases and generalist predators
Authors: Pringle Henrietta , Wilson Mark , Calladine John , Siriwardena Gavin 
Published: July 2019

Abstract

The release of more than 40 million captive‐bred pheasants and red‐legged partridges in Britain annually represents a significant addition to the potential food resource base for predators and scavengers. If this extra food availability subsidizes predator populations, gamebird releases could increase predation pressure on other wild birds, affecting their populations.

Using three extensive datasets, we examined the spatial relationships between reared and free‐roaming gamebirds (pheasant Phasianus colchicus and red‐legged partridge Alectoris rufa), and explored spatial and temporal associations between these gamebirds and five species of avian predator (buzzard Buteo buteo, jay Garrulus glandarius, raven Corvus corax, magpie Pica pica and hooded Corvus cornix and carrion Corvus corone crows combined) in lowland rural Britain.

Patterns of spatial variation in the abundance of free‐roaming gamebirds across Britain appear to be largely determined by gamebird releases, over and above any effects of land use or habitat. Predominantly positive associations between gamebird abundance (both reared and free‐roaming) and the abundance and inter‐annual population growth rates of predators tested suggest that large‐scale variation in avian predator populations may be positively affected by gamebird releases.

Synthesis and applications. The positive associations between large‐scale gamebird release and predator populations shown here may have implications for prey populations if the releases cause increased predation pressure. If this occurs, game management could have an indirect negative impact on some prey species partially counteracting previously reported positive or benign effects of game management on wider biodiversity. Overall impacts of gamebird releases are likely to be determined by complex interactions between multiple factors, including induced predation pressure, better understanding of which would be possible with compulsory recording of releases and numbers of predators killed. Restriction of releases warrants further investigation and consideration as a potential conservation tool for wild bird populations.
Sustaining the HIV care provider workforce: Medical Monitoring Project HIV Provider Survey, 2013‐2014
Authors: Weiser John , Chen Guangnan , Beer Linda , Boccher‐Lattimore Daria , Armstrong Wendy , Kurth Ann , Shouse R. Luke 
Published: July 2019

AbstractObjectiveTo describe delivery of recommended HIV care and work satisfaction among infectious disease (ID) physicians, non‐ID physicians, nurse practitioners (NPs), and physician assistants (PAs).Data SourcesMedical Monitoring Project 2013‐2014 HIV Provider Survey.Study DesignPopulation‐based complex sample survey.Data Collection/Analysis MethodsWe surveyed 2208 HIV care providers at 505 US HIV care facilities and computed weighted percentages of provider characteristics, stratified by provider type. Rao‐Scott chi‐square tests and logistic regression used to compare characteristics of ID physicians with each other provider type.Principal FindingsThe adjusted provider response rate was 64 percent. Among US HIV care providers, 45 percent were ID physicians, 35 percent non‐ID physicians, 15 percent NPs, and 5 percent PAs. Satisfaction with administrative burden was lowest among non‐ID physicians (27 percent). Compared with ID physicians, satisfaction with remuneration was lower among non‐ID physicians and higher among NPs (37, 28, and 51 percent, respectively). NPs were more likely than ID physicians to report performing four of six services that are key to providing comprehensive HIV care, but more NPs planned to leave clinical practice within 5 years (19 vs 7 percent).ConclusionAddressing physician dissatisfaction with remuneration and administrative burden could help prevent a provider shortage. Strengthening the role of NPs may help sustain a high‐quality workforce.