bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Healthy Nevada Project: rapid recruitment for population health study
Authors: Grzymski Joseph J , Coppes Max J , Metcalf Jim , Galanopoulos Christos , Rowan Chris , Henderson Michele , Read Robert , Reed Harry , Lipp Bruce , Miceli Dave , Rybarski Susan , Slonim Anthony 
Published: January 2018

AbstractBackgroundNevada ranks in the bottom half of overall health rankings in the United States. The majority of residents of Northern Nevada live in Washoe County, which is confounded with high age-adjusted death rates for heart disease, cancer and chronic lower respiratory disease.MethodsSaliva as a source of DNA was collected from adults in Northern Nevada as the first phase of a much larger (100,000 participants) effort to contribute to comprehensive population health studies in Nevada. The personal genetics company 23andMe was used to genotype the first 10,250 participants and deliver their custom ancestry, traits, wellness, and carrier status reports.ResultsThe study was announced by Governor Brian Sandoval on September 15, 2016 and within two days the registration of 9,700 volunteers for an appointment was complete. Processing of 9,344 participants was achieved in 3 months, with a no-show rate of just over 11%. The participant population was skewed to female and was less racially diverse than the population.ConclusionDNA genotyping was administered free-of-charge and the patient population was representative of the socio-economic diversity in northern Nevada – indicating that free genetic testing is of interest to a broad swath of the population and a powerful motivator for comprehensive population health study research.
Near Perfect Neural Critic from Motor Cortical Activity Toward an Autonomously Updating Brain Machine Interface
Authors: An Junmo , Yadav Taruna , Ahmadi Mohammad Badri , Tarigoppula Venkata S Aditya , Francis Joseph Thachil 
Published: January 2018

AbstractWe are developing an autonomously updating brain machine interface (BMI) utilizing reinforcement learning principles. One aspect of this system is a neural critic that determines reward expectations from neural activity. This critic is then used to update a BMI decoder towards an improved performance from the user’s perspective. Here we demonstrate the ability of a neural critic to classify trial reward value given activity from the primary motor cortex (M1), using neural features from single/multi units (SU/MU), and local field potentials (LFPs) with prediction accuracies up to 97% correct. A nonhuman primate subject conducted a cued center out reaching task, either manually, or observationally. The cue indicated the reward value of a trial. Features such as power spectral density (PSD) of the LFPs and spike-field coherence (SFC) between SU/MU and corresponding LFPs were calculated and used as inputs to several classifiers. We conclude that hybrid features of PSD and SFC show higher classification performance than PSD or SFC alone (accuracy was 92% for manual tasks, and 97% for observational). In the future, we will employ these hybrid features towards our autonomously updating BMI.
Discovery and optimization of piperazine-1-thiourea-based human phosphoglycerate dehydrogenase inhibitors
Authors: Rohde Jason M. , Brimacombe Kyle R. , Liu Li , Pacold Michael E. , Yasgar Adam , Cheff Dorian M. , Lee Tobie D. , Rai Ganesha , Baljinnyam Bolormaa , Li Zhuyin , Simeonov Anton , Hall Matthew D. , Shen Min , Sabatini David M. , Boxer Matthew B. 
Published: January 2018

AbstractProliferating cells, including cancer cells, obtain serine both exogenously and via the metabolism of glucose. By catalyzing the first, rate-limiting step in the synthesis of serine from glucose, phosphoglycerate dehydrogenase (PHGDH) controls flux through the biosynthetic pathway for this important amino acid and represents a putative target in oncology. To discover inhibitors of PHGDH, a coupled biochemical assay was developed and optimized to enable high-throughput screening for inhibitors of human PHGDH. Feedback inhibition was minimized by coupling PHGDH activity to two downstream enzymes (PSAT1 and PSPH), providing a significant improvement in enzymatic turnover. Further coupling of NADH to a diaphorase/resazurin system enabled a red-shifted detection readout, minimizing interference due to compound autofluorescence. With this protocol, over 400,000 small molecules were screened for PHGDH inhibition, and following hit validation and triage work, a piperazine-1-thiourea was identified. Following rounds of medicinal chemistry and SAR exploration, two probes (NCT-502 and NCT-503) were identified. These molecules demonstrated improved target activity and encouraging ADME properties, enabling both in vitro and in vivo assessment of the biological importance of PHGDH, and its role in the fate of serine in PHGDH-dependent cancer cells.
Size-dependent segregation controls macrophage phagocytosis of antibody-opsonized targets
Authors: Bakalar Matthew H. , Joffe Aaron M. , Schmid Eva M. , Son Sungmin , Podolski Marija , Fletcher Daniel A. 
Published: January 2018

AbstractMacrophages protect the body from damage and disease by targeting antibody-opsonized cells for phagocytosis. Though antibodies can be raised against antigens with diverse structures, shapes, and sizes, it is unclear why some are more effective at triggering antibody-dependent phagocytosis than others. Here we quantitatively define an antigen height threshold that regulates phagocytosis of both engineered and cancer-specific antigens by macrophages. Using a reconstituted model of antibody-opsonized target cells, we find that phagocytosis is dramatically impaired for antigens that position antibodies >10 nm from the target surface. Increasing antigen height allows for co-localization of Fc receptors and the inhibitory phosphatase CD45 at the cell-cell interface, which reduces Fc receptor phosphorylation, and inhibits phagocytosis. Our work shows that close contact between macrophage and target cell is a requirement for efficient phagocytosis, suggesting that therapeutic antibodies should target short antigens in order to trigger Fc receptor activation through size-dependent physical segregation.
Assessment of the CTCF Binding Sites and Repeat-Positions Upstream the Human H19 Gene
Authors: Bina Minou 
Published: January 2018

AbstractThe human H19 and IGF2 genes share an Imprinting Control Region (ICR) that regulates gene expression in a parent-of-origin dependent manner. Understanding of the ICR sequence organization is critical to accurate localization of disease-associated abnormalities including Beckwith-Wiedemann and Silver-Russell syndromes. Previous studies established that the ICR of the H19 - IGF2 imprinted domain included several repeated DNA segments. Using BLAST, BLAT, and Clustal Omega, I conducted detailed sequence comparisons to evaluate the annotation of the unique-repeats upstream of the H19 transcription start site (TSS) and to investigate the extent of similarities among the various repeats. Initial analyses confirmed the existence of two DNA segments consisting of two types of repeats (A and B). However, I find that one of the repeats (B7) is unlikely to be a partial repeat. I provide the genomic positions of the various repeats in the build hg19 of the human genome. I also evaluated the previously predicted CTCF sites (1 to 7) in the context of the ENCODE data: including the positions of DNase I HS clusters and results of ChIP assays. My evaluations did not support the existence of CTCF site 5. Furthermore, the ENCODE data revealed a previously unknown chromatin boundary (consisting of CTCF, RAD21, and SMC3), in a CpG island (CpG27) between the A1 repeat and the H19 TSS. Furthermore, a sequence within this boundary corresponds to a newly discovered CTCF site (I named it CTCF site 8). My discovery of this chromatin boundary in CpG27 entails mechanistic implications.
CSF biomarkers are differentially related to structural and functional changes in dementia of the Alzheimer’s type
Authors: Malpas Charles B , Saling Michael M , Velakoulis Dennis , Desmond Patricia , Hicks Rodney J , Zetterberg Henrik , Blennow Kaj , O’Brien Terence J. 
Published: January 2018

AbstractThe two cardinal pathologies of Alzheimer’s disease (AD) develop according to distinct anatomical trajectories. Cerebral tau-related pathology first accumulates in the mesial temporal region, while amyloid-related pathology first appears in neocortex. The eventual distributions of these pathologies reflect their anatomical origins. An implication is that the cardinal pathologies might exert preferential effects on the structurofunctional brain changes observed in AD. We investigated this hypothesis in 39 patients with dementia of the Alzheimer’s type. Interrelationships were analysed between cerebrospinal fluid (CSF) biomarkers of the cardinal pathologies, volumetric brain changes using magnetic resonance imaging, and brain metabolism using [18F]-FDG-PET. Amyloid-related pathology was preferentially associated with structurofunctional changes in the precuneus and lateral temporal regions. Tau-related pathology was not associated with changes in these regions. These findings support the hypothesis that tau- and amyloid-pathology exert differential effects on structurofunctional changes in the AD brain. These findings have implications for future therapeutic trials and hint at a more complex relationship between the cardinal pathologies and disruption of brain networks.
Improved prediction of fungal effector proteins from secretomes with EffectorP 2.0
Authors: Sperschneider Jana , Dodds Peter N. , Gardiner Donald M. , Singh Karam B. , Taylor Jennifer M. 
Published: January 2018

AbstractPlant-pathogenic fungi secrete effector proteins to facilitate infection. We describe extensive improvements to EffectorP, the first machine learning classifier for fungal effector prediction. EffectorP 2.0 is now trained on a larger set of effectors and utilizes a different approach based on an ensemble of classifiers trained on different subsets of negative data, offering different views on classification. EffectorP 2.0 achieves accuracy of 89%, compared to 82% for EffectorP 1.0 and 59.8% for a small size classifier. Important features for effector prediction appear to be protein size, protein net charge as well as the amino acids serine and cysteine. EffectorP 2.0 decreases the number of predicted effectors in secretomes of fungal plant symbionts and saprophytes by 40% when compared to EffectorP 1.0. However, EffectorP 1.0 retains value and combining EffectorP 1.0 and 2.0 results in a stringent classifier with low false positive rate of 9%. EffectorP 2.0 predicts significant enrichments of effectors in 12 out of 13 sets of infection-induced proteins from diverse fungal pathogens, whereas a small cysteine-rich classifier detects enrichment only in 7 out of 13. EffectorP 2.0 will fast-track prioritization of high-confidence effector candidates for functional validation and aid in improving our understanding of effector biology. EffectorP 2.0 is available at http://effectorp.csiro.au.
FoodEstNet: Estimating True Food Consumption with Machine Learning
Authors: Akogo Darlington A. , Danquah Joseph B 
Published: January 2018

AbstractWe developed a Machine Learning/Artificial Intelligence model that estimates how much of a food type a person truly consumes. People tend to underestimate how much they consume which makes the work of nutritionists and dietitians difficult since they rely on food estimates for food portion size control and nutritional management of diseases. We trained an XGBoost model to estimate how much a patient truly consumes based on Age, Sex, BMI, socioeconomic status and perceived consumption.
Fatigue influences the recruitment, but not structure, of muscle synergies
Authors: Ortega-Auriol P.A. , Besier T.F. , Byblow W.D. , McMorland A.J.C. 
Published: January 2018

AbstractThe development of fatigue elicits multiple adaptations from the neuromuscular system. Muscle synergies are common patterns of neuromuscular activation that have been proposed as the building blocks of human movement. We wanted to identify possible adaptations of muscle synergies to the development of fatigue in the upper limb. Recent studies have reported that synergy structure remains invariant during the development of fatigue, but these studies did not examine isolated synergies. We propose a novel approach to characterize synergy adaptations to fatigue by taking advantage of the spatial tuning of synergies. This approach allows improved identification of changes to individual synergies that might otherwise be confounded by changing contributions of overlapping synergies. To analyse upper limb synergies we applied non-negative matrix factorization to 14 EMG signals from muscles of 11 participants performing isometric contractions. A preliminary multidirectional task was used to identify synergy directional tuning. A subsequent fatiguing task was designed to fatigue the participants in their synergies’ preferred directions. Both tasks provided virtual reality feedback of the applied force direction and magnitude, and were performed at 40% of each participant’s maximal voluntary force. Five epochs were analysed throughout the fatiguing task to identify progressive changes of EMG amplitude, median frequency, synergy structure, and activation coefficients. Three to four synergies were sufficient to account for the variability contained in the original data. Synergy structure was conserved with fatigue, but interestingly synergy activation coefficients decreased on average by 24.5% with fatigue development. EMG amplitude did not change systematically with fatigue, whereas EMG median frequency consistently decreased across all muscles. These results support the notion of a neuromuscular modular organization as the building blocks of human movement, with adaptations to synergy recruitment occurring with fatigue. When synergy tuning properties are considered, the reduction of activation of muscle synergies may be a reliable marker to identify fatigue.
Analysis of mycobacterial infection-induced changes to host lipid metabolism in a zebrafish infection model reveals a conserved role for LDLR in infection susceptibility
Authors: Johansen Matt D. , Hortle Elinor , Kasparian Joshua A. , Romero Alejandro , Novoa Beatriz , Figueras Antonio , Britton Warwick J. , de Silva Kumudika , Purdie Auriol C. , Oehlers Stefan H. 
Published: January 2018

AbstractChanges to lipid metabolism are well-characterised consequences of human tuberculosis infection but their functional relevance are not clearly elucidated in these or other host-mycobacterial systems. The zebrafish-Mycobacterium marinum infection model is used extensively to model many aspects of human-M. tuberculosis pathogenesis but has not been widely used to study the role of infection-induced lipid metabolism. We find mammalian mycobacterial infection-induced alterations in host Low Density Lipoprotein metabolism are conserved in the zebrafish model of mycobacterial pathogenesis. Depletion of LDLR, a key lipid metabolism node, decreased M. marinum burden, and corrected infection-induced altered lipid metabolism resulting in decreased LDL and reduced the rate of macrophage transformation into foam cells. Our results demonstrate a conserved role for infection-induced alterations to host lipid metabolism, and specifically the LDL-LDLR axis, across host-mycobacterial species pairings.FundingThis work was supported by the Australian National Health and Medical Research Council (APP1099912 and APP1053407 to S.H.O.); Meat and Livestock Australia (P.PSH. 0813 to A.C.P. and K. dS); the Marie Bashir Institute for Infectious Diseases and Biosecurity (grant to S.H.O., A.C.P. and K. dS); the Kenyon Family Foundation Inflammation Award (grant to S.H.O.); the University of Sydney (fellowship to S.H.O.); Consellería de Economía, Emprego e Industria (GAIN), Xunta de Galicia (grant IN607B 2016/12 to Institute of Marine Research (IIM-CSIC)).
Genetic Signatures of Lipid Metabolism Evolution in Cetacea
Authors: Endo Yoshinori , Kamei Ken-ichiro , Inoue-Murayama Miho 
Published: January 2018

AbstractIn mammalian evolutionary history, Cetacea (whales, dolphins, and porpoises) achieved astonishing success by adapting to an aquatic environment. One unique characteristic of cetaceans, contributing to this adaptive success, is efficient lipid utilization. Here we report comparative genetic analysis of aquatic and terrestrial Cetartiodactyla using 144 genes associated with lipid metabolism. We analyzed mutation rate, amino acid substitution, and metabolic pathways using genetic data publicly available. Our test detected 18 positively selected genes in Cetacea compared to 13 in Bovidae with little overlap between the lineages. We identified lineage-specific patterns of amino acid substitutions and functional domain that were mutually exclusive between cetaceans and bovids, supporting divergent evolution of lipid metabolism since the divergence of these taxa from a common ancestor. Moreover, a pathway analysis showed that the identified genes in cetaceans were associated with lipid digestion, lipid storage, and energy producing pathways. This study emphasizes the evolutionary context of lipid metabolism modification of cetaceans and provides a foundation for future studies of elucidating the adapted biological mechanisms of cetacean lipid metabolism and a framework for incorporating ecological context into studies aimed at investigating adaptive evolution.
5-hydroxy-4′-nitro-7-propionyloxy-genistein inhibited invasion and metastasis via inactivating wnt/β-catenin signal pathway in human endometrial carcinoma JEC cells
Authors: Bai Jun , Yang Binjian , Luo Xin 
Published: January 2018

ABSTRACTChemotherapy has been demonstrating more important roles in the treatment of carcinoma, but drug resistance and side effects restrict its usage in clinic, so developing new type of drug with low side effects and low-drug resistance has become a hot researching spot. The present study aimed to investigate the anticancer effects of 5-hydroxy-4’-nitro-7-propionyloxy-genistein (HNPG) and elucidate its underlying molecular mechanism. The inhibitory effects of cell viability of HNPG were detected using MTT assay, flat plate clone formation method and Transwell assay. The distribution of cell cycle was analyzed using FCM method. The morphological alteration, root-mean-squared roughness (Rq), average roughness (Ra), Young's modulus and adhesive force were measured by AFM. qRT-PCR and western blotting analysis were used to explore the possible molecular mechanism. It was found that HNPG presented with dramatic activity against JEC cellsin vitro, inhibited the proliferation and colony formation, attenuated invasion and migration ability, arrested cell cycle in G1 phase in dose-dependent manner. Simultaneously, cell body shrunk and pseudopod structure retracted, Rq and Ra reduced, Young's modulus and adhesive force increased, accompanied by β-catenin, C-myc, Cyclin D1, MMP-2, MMP-7 and MMP-9 down-regulated. In summary, HNPG may be a novel candidate for chemotherapeutic drug.
Differential antiviral activities of RSV inhibitors in human airway epithelium
Authors: Mirabelli Carmen , Jaspers Martine , Boon Mieke , Jorissen Mark , Koukni Mohamed , Bardiot Dorothee , Chaltin Patrick , Marchand Arnaud , Neyts Johan , Jochmans Dirk 
Published: January 2018

ABSTRACTWe report the use of reconstituted 3D-human airway epithelium cells of bronchial origin (HuAEC) in an air-liquid interface to study respiratory syncytial virus (RSV) infection and to assess the efficacy of RSV inhibitors in (pre-)clinical development. RSV-A replicates efficiently in HuAEC and viral RNA is shed for weeks after infection. RSV infection reduces the ciliary beat frequency of the ciliated cells as of 4 days post infection, with complete ciliary dyskinesia observed by day 10. Treatment with RSV fusion inhibitors resulted in an antiviral effect only when added at the time of infection. In contrast, the use of replication inhibitors (both nucleoside and non-nucleosides) elicited a marked antiviral effect even when start of treatment was delayed until one or even three days after infection. Levels of the inflammation marker RANTES (mRNA) increased ∼200-fold in infected-untreated cultures (at three weeks post infection), but levels were comparable to those of uninfected cultures in the presence of PC-876, a RSV-replication inhibitor, demonstrating that an efficient antiviral treatment inhibits virus induced inflammation in this model. Overall, HuAEC offer a robust and physiologically relevant model to study RSV replication and to assess the efficacy of antiviral compounds.
TNscope: Accurate Detection of Somatic Mutations with Haplotype-based Variant Candidate Detection and Machine Learning Filtering
Authors: Freed Donald , Pan Renke , Aldana Rafael 
Published: January 2018

AbstractDetection of somatic mutations in tumor samples is important in the clinic, where treatment decisions are increasingly based upon molecular diagnostics. However, accurate detection of these mutations is difficult, due in part to intra-tumor heterogeneity, contamination of the tumor sample with normal tissue and pervasive structural variation. Here, we describe Sentieon TNscope, a haplotype-based somatic variant caller with increased accuracy relative to existing methods. An early engineering version of TNscope was used in our submission to the most recent ICGC-DREAM Somatic Mutation calling challenge. In that challenge, TNscope is the leader in accuracy for SNVs, indels and SVs. To further improve variant calling accuracy, we combined the improvements in the variant caller with machine learning. We benchmarked TNscope using in-silico mixtures of well-characterized Genome in a Bottle (GIAB) samples. TNscope displays higher accuracy than the other benchmarked tools and the accuracy is substantially improved by the machine learning model.