bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing Community Detection Methods in Brain Functional Connectivity Networks
Authors: Vangimalla Reddy Rani , Sreevalsan-Nair Jaya 
Published: February 2020

AbstractBrain functional networks are essential for understanding functional connectome. Computing the temporal dependencies between the regions of brain activities of functional magnetic resonance imaging (fMRI) gives us the functional connectivity between the regions. The pairwise connectivities in matrix form correspond to the functional network (fNet), also referred to as a functional connectivity network (FCN). We start with analyzing a correlation matrix, which is an adjacency matrix of the FCN. In this work, we perform a case study of comparison of different analytical approaches in finding node-communities of the brain network. We use five different methods of community detection, out of which two methods are implemented on the network after filtering out the edges with weight below a predetermined threshold. We additionally compute and observe the following characteristics of the outcomes: (i)modularityof the communities, (ii) symmetrical node-partition between the left and right hemispheres of the brain, i.e.,hemispheric symmetry, and (iii)hierarchical modular organization. Our contribution is in identifying an appropriate test-bed for comparison of outcomes of approaches using different semantics, such as network science, information theory, multivariate analysis, and data mining.
Association between ocular biometrical parameters and diabetic retinopathy in Chinese adults with type 2 diabetes mellitus
Authors: Wang Lanhua , Liu Sen , Wang Wei , He Miao , Mo Zhiyin , Gong Xia , Xiong Kun , Li Yuting , Huang Wenyong 
Published: February 2020

AbstractPurposeTo investigate the association between ocular biometrical parameters and diabetic retinopathy (DR) in ocular treatment naive patients with diabetes.MethodsThis cross-sectional study recruited type 2 diabetes mellitus patients with no history of ocular treatment in Guangzhou, China. The ocular biometrical parameters were obtained by Lenstar, including corneal diameter, central corneal thickness (CCT), corneal curvature (CC), anterior chamber depth (ACD), lens thickness (LT), and axial length (AL). The lens power and axial length-to-cornea radius ratio (AL/CR ratio) were calculated. Spherical equivalent (SE) was determined by auto-refraction after pupil dilation. Multivariate logistic regression analyses were performed to explore the associations of ocular biometry with any DR and vision threatening DR (VTDR).ResultsA total of 1838 patients were included in the final analysis, involving 145 5(79.2%) patients without DR and 383(20.8%) patients with DR. After adjusting confounding factors, any DR was independently associated with AL (OR = 0.84 per 1 mm increase, 95%CI: 0.74, 0.94), lens power (OR = 0.9951 per 1 D increase, 95%CI: 0.9904, 0.9998), and AL/CR ratio (OR = 0.26 per 1 increase, 95%CI: 0.10-0.70). Similarly, the presence of VTDR was independently related to AL (OR = 0.67 per 1 mm increase, 95%CI: 0.54-0.85), lens power (OR = 0.99 per 1 D increase, 95%CI: 0.98, 0.997), and AL/CR ratio (OR = 0.04 per 1 increase, 95%CI: 0.01, 0.25). The CC, corneal diameter, and refractive status were not significantly correlated with presence of DR or VTDR.ConclusionLonger AL, deeper ACD, higher lens power, and higher AL/CR ratio may be protective factors against DR. Considering the high prevalence of myopia in the Chinese juvenile population, it is worth paying attention to how the incidence of DR in this generation may change over time.
Low-cost and versatile electrodes for extracellular chronic recordings in rodents
Authors: Franca Arthur S C , van Hulten Josephus A , Cohen Michael X 
Published: February 2020

AbstractElectrophysiological data are used to investigate fundamental properties of brain function, its relation to cognition, and its dysfunction in diseases. The development of reliable and open-source systems for electrophysiological data acquisition is decreasing the total cost of constructing and operating an electrophysiology laboratory, and facilitates low-cost methods to extract and analyze the data (Siegle et al., 2017). Here we detail our method of building custom-designed low-cost electrodes. These electrodes can be customized and manufactured by any researcher to address a broad set of research questions, further decreasing the final cost of an implanted animal. Finally, we present data showing such an electrode has a good signal quality to record LFP.
Discriminating between sleep and exercise-induced fatigue using computer vision and behavioral genetics
Authors: Schuch Kelsey N. , Govindarajan Lakshmi Narasimhan , Guo Yuliang , Baskoylu Saba N. , Kim Sarah , Kimia Benjamin , Serre Thomas , Hart Anne C. 
Published: February 2020

AbstractFollowing prolonged swimming,Caenorhabditis eleganscycle between active swimming bouts and inactive quiescent bouts. Swimming is exercise forC. elegansand here we suggest that inactive bouts are a recovery state akin to fatigue. Previously, analysis of exercise-induced quiescent (EIQ) bouts relied on laborious manual observation, as existing automated analysis methods forC. elegansswimming either cannot analyze EIQ bouts or fail to accurately track animal posture during these bouts. It is known that cGMP-dependent kinase (PKG) activity plays a conserved role in sleep, rest, and arousal. UsingC. elegansEGL-4 PKG, we first validate a novel learning-based computer vision approach to automatically analyzeC. eleganslocomotory behavior and distinguish between activity and inactivity during swimming for long periods of time. We find thatC. elegansEGL-4 PKG function predicts EIQ first bout timing, fractional quiescence, bout number, and bout duration, suggesting that previously described pathways are engaged during EIQ bouts. However, EIQ bouts are likely not sleep as animals are feeding during the majority of EIQ bouts. We find that genetic perturbation of neurons required for otherC. eleganssleep states also does not alter EIQ dynamics. Additionally, we find that EIQ onset is sensitive to age and DAF-16 FOXO function. In summary, we have validated a new behavioral analysis software that enabled a quantitative and detailed assessment of swimming behavior, including EIQ. We found novel EIQ defects in aged animals and animals with mutations in a gene involved in stress tolerance. We anticipate that further use of this software will facilitate the analysis of genes and pathways critical for fatigue and otherC. elegansbehaviors.
Insecticide-free trapping bed-net can mitigate insecticide resistance threat in malaria vector control strategies
Authors: Mouhamadou Chouaibou S. , Luan Kun , Fodjo Behi Kouadio , West Andre , McCord Marian , Apperson Charles S. , Roe R. Michael 
Published: February 2020

AbstractMosquito-borne malaria kills 429,000 people each year with the problem acute in sub-Saharan Africa. The successes gained with long-lasting pyrethroid treated bed-nets is now in jeopardy because of wide-spread, pyrethroid-resistance in mosquitoes. Using crowd modeling theory normalized for standard bed-net architecture, we were able to design an attract-trap-kill mechanism for mosquitoes that does not require insecticides. Using three-dimensional polyester knitting and heat fixation, trap funnels were developed with high capture efficacy, no egression under worst-case laboratory conditions, and greater durability than current bed-nets sold. Field testing in Africa in WHO huts with Gen1-3 T (trap)-Nets validated our model, and as predicted, Gen3 had the highest efficacy with a 4.3-fold greater trap-kill rate with no deterrence or repellency compared to Permanet 2.0, the most common bed-net in Africa. A T-Net population model was developed based on field data to predict community level mosquito control compared to a pyrethroid bed-net. This model showed the Gen3 T-Net under field conditions in Africa against pyrethroid resistant mosquitoes was 12.7-fold more efficacious than single chemical, pyrethroid treated nets, demonstrating significantly greater mosquito control using bed-nets without insecticides.
Long-term Behavioural Rewriting of Maladaptive Drinking Memories via Reconsolidation-Update Mechanisms
Authors: Gale Grace. , Hennessy Vanessa E. , Walsh Katie. , Kamboj Sunjeev K. , Das Ravi. K. 
Published: February 2020

ABSTRACTBackgroundAlcohol use disorders can be conceptualised as a learned pattern of maladaptive alcohol-consumption behaviours. The memories encoding these behaviours centrally contribute to long-term excessive alcohol consumption and are a key therapeutic target. The transient period of memory instability sparked during memory reconsolidation offers a therapeutic window to directlyrewritethese memories using targeted behavioural interventions. However, clinically-relevant demonstrations of the efficacy of this approach are few. We examined key retrieval parameters for destabilising naturalistic drinking memories and the ability of subsequent counterconditioning to effect long-term reductions in drinking.MethodsHazardous/harmful beer-drinking volunteers (N=120) were factorially randomised to retrieve (RET) or not retrieve (No RET) alcohol reward memories with (PE) or without (No PE) alcohol reward prediction error. All participants subsequently underwent disgust-basedcounterconditioningof drinking cues. Acute responses to alcohol were assessed pre- and post-manipulation and drinking levels assessed up to 9 months.ResultsGreater long-term reductions in drinking were found when counterconditioning was conducted following retrieval (with and without PE), despite a lack of short-term group differences in motivational responding to acute alcohol. Large variability in acute levels of learning during counterconditioning were noted. ‘Responsiveness’ to counterconditioning predicted subsequent responses to acute alcohol inRET+PEonly, consistent with reconsolidation-update mechanisms.ConclusionsThe longevity of behavioural interventions designed to reduce problematic drinking levels may be enhanced by leveraging reconsolidation-update mechanisms to rewrite maladaptive memory. However, inter-individual variability in levels of corrective learning is likely to determine the efficacy of reconsolidation-updating interventions and should be considered when designing and assessing interventions.
The Druggable Genome as Seen from the Protein Data Bank
Authors: Wang Jiayan , Yazdani Setayesh , Han Ana , Schapira Matthieu 
Published: February 2020

AbstractAlmost twenty years after the human genome was sequenced, the wealth of data produced by the international human genome project has not translated into a significantly improved drug discovery enterprise. This is in part because small molecule modulators that could be used to explore the cellular function of their target proteins and to discover new therapeutic opportunities are only available for a limited portion of the human proteome. International efforts are underway to develop such chemical tools for a few, specific protein families, and a “Target 2035” call to enable, expand and federate these efforts towards a comprehensive chemical coverage of the druggable genome was recently announced. But what is the druggable genome? Here, we systematically review structures of human proteins bound to drug-like ligands available from the protein databank (PDB) and use ligand desolvation upon binding as a druggability metric to draw a landscape of the human druggable genome. We show that the vast majority of druggable protein families, including some highly populated and deeply associated with cancer according to genomic screens, are almost orphan of small molecule ligands, and propose a list of 46 druggable domains representing 3440 human proteins that could be the focus of large chemical probe discovery efforts.
Variation in recombination rate affects detection of outliers in genome scans under neutrality
Authors: Booker Tom R. , Yeaman Sam , Whitlock Michael C. 
Published: February 2020

AbstractGenome scans can potentially identify genetic loci involved in evolutionary processes such as local adaptation and gene flow. Here, we show that recombination rate variation across a neutrally evolving genome gives rise to mixed sampling distributions of meanFST, a common population genetic summary statistic. In particular, we show that in regions of low recombination the distribution ofestimates have more variance and a longer tail than in more highly recombining regions. Determining outliers from the genome-wide distribution without taking local recombination rate into consideration may therefore increase the frequency of false positives in low recombination regions and be overly conservative in more highly recombining ones. We perform genome-scans on simulated and empiricalDrosophila melanogasterdatasets and, in both cases, find patterns consistent with this neutral model. Similar patterns are observed for other summary statistics used to capture variation in the coalescent process. Linked selection, particularly background selection, is often invoked to explain heterogeneity inacross the genome, but here we point out that even under neutrality, statistical artefacts can arise due to variation in recombination rate. Our results highlight a flaw in the design of genome scan studies and suggest that without estimates of local recombination rate, interpreting the genomic landscape of any summary statistic that captures variation in the coalescent process will be very difficult.
A framework for implementing metaheuristic algorithms using intercellular communication
Authors: Gutiérrez Martín , Ortiz Yerko , Carrión Javier 
Published: February 2020

ABSTRACTMetaheuristic procedures (MH) have been a trend driving Artificial Intelligence (AI) researchers for the past 50 years. A variety of tools and applications (not only in Computer Science) stem from these techniques. Also, MH frequently rely on evolution, a trademark process involved in cell colony growth. Generally, MH are used to approximate the solution to difficult problems but require a large amount of computational resources. Cell colonies harboring synthetic distributed circuits using intercell communication offer a direction for tackling this problem, as they process information in a massively parallel fashion. In this work, we propose a framework that maps MH elements to synthetic circuits in growing cell colonies. The framework relies on cell-cell communication mechanisms such as quorum sensing (QS) and bacterial conjugation. As a proof-of-concept, we also implemented the workflow associated to the framework, and tested the execution of two specific MH (Genetic Algorithms and Simulated Annealing) encoded as synthetic circuits on thegrosimulator. Furthermore, we show an example of how our framework can be extended by implementing another kind of computational model: The Cellular Automaton. This work seeks to lay the foundations of mappings for implementing AI algorithms in a general manner using Synthetic Biology constructs in cell colonies.
ContamLD: Estimation of Ancient Nuclear DNA Contamination Using Breakdown of Linkage Disequilibrium
Authors: Nakatsuka Nathan , Harney Éadaoin , Mallick Swapan , Mah Matthew , Patterson Nick , Reich David 
Published: February 2020

AbstractWe report a method,ContamLD, for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of contaminant DNA, leveraging the idea that contaminants should have haplotypes uncorrelated to those of the studied individual. Using simulated data, we confirm thatContamLDaccurately infers contamination rates with low standard errors (e.g. less than 1.5% standard error in cases with <10% contamination and data from at least 500,000 sequences covering SNPs). This method is optimized for application to aDNA, leveraging characteristic aDNA damage patterns to provide calibrated contamination estimates. Availability:https://github.com/nathan-nakatsuka/ContamLD.
Cohorting KPC+ Klebsiella pneumoniae (KPC-Kp) positive patients – a genomic exposé of cross-colonization hazards in a long-term acute care hospital (LTACH)
Authors: Hawken Shawn E. , Hayden Mary K. , Lolans Karen , Yelin Rachel D. , Weinstein Robert A. , Lin Michael Y. , Snitkin Evan S. 
Published: February 2020

AbstractObjectiveCohorting patients who are colonized or infected with multidrug-resistant organisms (MDROs) has been demonstrated to protect uncolonized patients from acquiring MDROs in healthcare settings. A neglected aspect of cohorting is the potential for cross-transmission within the cohort and the possibility of colonized patients acquiring secondary isolates with additional antibiotic resistance traits. We searched for evidence of cross-transmission of KPC+ Klebsiella pneumoniae (KPC-Kp) colonization among cohorted patients in a long-term acute care hospital (LTACH), and evaluated the impact of secondary acquisitions on resistance potential.DesignGenomic epidemiological investigationSettingA high-prevalence LTACH during a bundled intervention that included cohorting KPC-Kp-positive patients.MethodsWhole-genome sequencing (WGS) and location data were analyzed to identify potential cases of cross-transmission between cohorted patients.ResultsSecondary KPC-Kp isolates from 19 of 28 admission-positive patients were more closely related to another patient’s isolate than to their own admission isolate. In 14 of these 19 cases there was strong genomic evidence for cross-transmission (<10 SNVs) and the majority of these patients occupied shared cohort floors (12 cases) or rooms (5 cases) at the same time. Of the 14 patients with strong genomic evidence of acquisition, 12 acquired antibiotic resistance genes not found in their primary isolates.ConclusionsAcquisition of secondary KPC-Kp isolates carrying distinct antibiotic resistance genes was detected in nearly half of cohorted patients. These results highlight the importance of healthcare provider adherence to infection prevention protocols within cohort locations, and motivate future studies to assess whether multiple-strain acquisition increases risk of adverse patient outcomes.
Clonal Evolution of Acute Myeloid Leukemia Revealed by High-Throughput Single-Cell Genomics
Authors: Morita Kiyomi , Wang Feng , Jahn Katharina , Kuipers Jack , Yan Yuanqing , Matthews Jairo , Little Latasha , Gumbs Curtis , Chen Shujuan , Zhang Jianhua , Song Xingzhi , Thompson Erika , Patel Keyur , Bueso-Ramos Carlos , DiNardo Courtney D , Ravandi Farhad , Jabbour Elias , Andreeff Michael , Cortes Jorge , Konopleva Marina , Bhalla Kapil , Garcia-Manero Guillermo , Kantarjian Hagop , Beerenwinkel Niko , Navin Nicholas , Futreal P Andrew , Takahashi Koichi 
Published: February 2020

SummaryOne of the pervasive features of cancer is the diversity of mutations found in malignant cells within the same tumor; a phenomenon called clonal diversity or intratumor heterogeneity. Clonal diversity allows tumors to adapt to the selective pressure of treatment and likely contributes to the development of treatment resistance and cancer recurrence. Thus, the ability to precisely delineate the clonal substructure of a tumor, including the evolutionary history of its development and the co-occurrence of its mutations, is necessary to understand and overcome treatment resistance. However, DNA sequencing of bulk tumor samples cannot accurately resolve complex clonal architectures. Here, we performed high-throughput single-cell DNA sequencing to quantitatively assess the clonal architecture of acute myeloid leukemia (AML). We sequenced a total of 556,951 cells from 77 patients with AML for 19 genes known to be recurrently mutated in AML. The data revealed clonal relationship among AML driver mutations and identified mutations that often co-occurred (e.g.,NPM1/FLT3-ITD, DNMT3A/NPM1, SRSF2/IDH2,andWT1/FLT3-ITD) and those that were mutually exclusive (e.g.,NRAS/KRAS, FLT3-D835/ITD, andIDH1/IDH2) at single-cell resolution. Reconstruction of the tumor phylogeny uncovered history of tumor development that is characterized by linear and branching clonal evolution patterns with latter involving functional convergence of separately evolved clones. Analysis of longitudinal samples revealed remodeling of clonal architecture in response to therapeutic pressure that is driven by clonal selection. Furthermore, in this AML cohort, higher clonal diversity (≥4 subclones) was associated with significantly worse overall survival. These data portray clonal relationship, architecture, and evolution of AML driver genes with unprecedented resolution, and illuminate the role of clonal diversity in therapeutic resistance, relapse and clinical outcome in AML.
DNA Methylation Repels Binding of HIF Transcription Factors to Maintain Tumour Immunotolerance
Authors: D’anna Flora , Dyck Laurien Van , Xiong Jieyi , Zhao Hui , Berrens Rebecca V. , Smedt Julie De , Bieniasz-Krzywiec Pawel , Chandra Vikas , Schoonjans Luc , Matthews Jason , Minnoye Liesbeth , Qian Junbin , Amorim Ricardo , Khorasanizadeh Sepideh , Borre Marie De , Savvides Savvas N. , Simon Celeste , Carmeliet Peter , Reik Wolf , Rastinejad Fraydoon , Mazzone Massimiliano , Thienpont Bernard , Lambrechts Diether 
Published: February 2020

AbstractBackgroundHypoxia is pervasive in cancer and other diseases. Cells sense and adapt to hypoxia by activating hypoxia-inducible transcription factors (HIFs), but it is still an outstanding question why cell types differ in their transcriptional response to hypoxia.ResultsHere, we report that HIFs fail to bind CpG dinucleotides that are methylated in their consensus binding sequence, both inin vitrobiochemical binding assays andin vivostudies of differentially methylated isogenic cell lines. Based on in silico structural modelling, we show that 5-methylcytosine indeed causes steric hindrance in the HIF binding pocket. A model wherein cell-type-specific methylation landscapes, as laid-down by the differential expression and binding of other transcription factors under normoxia control cell-type-specific hypoxia responses is observed. We also discover ectopic HIF binding sites in repeat regions which are normally methylated. Genetic and pharmacological DNA demethylation, but also cancer-associated DNA hypomethylation, expose these binding sites, inducing HIF-dependent expression of cryptic transcripts. In line with such cryptic transcripts being more prone to cause double-stranded RNA and viral mimicry, we observe low DNA methylation and high cryptic transcript expression in tumours with high immune checkpoint expression, but not in tumours with low immune checkpoint expression, where they would compromise tumour immunotolerance. In a low-immunogenic tumour model, DNA demethylation upregulates cryptic transcript expression in a HIF-dependent manner, causing immune activation and reducing tumour growth.ConclusionsOur data elucidate the mechanism underlying cell-type specific responses to hypoxia, and suggest DNA methylation and hypoxia to underlie tumour immunotolerance.