bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Cycle Corrections in Discrete Time Markov Models: A Gaussian Quadrature Approach
Authors: Srivastava Tushar , Strong Mark , Stevenson Matthew D , Dodd Peter J 
Published: July 2020

AbstractIntroductionDiscrete-time Markov models are widely used within health economic modelling. Analyses usually associate costs and health outcomes with health states and calculate totals for each decision option over some timeframe. Frequently, a correction method (e.g. half-cycle correction) is applied to unadjusted model outputs to yield an approximation to an assumed underlying continuous-time Markov model. In this study, we introduce a novel approximation method based on Gaussian Quadrature (GQ).MethodsWe exploited analytical results for time-homogeneous Markov chains to derive a new GQ-based approximation, which is applied to an unadjusted discrete-time model output. The GQ method approximates a continuous-time Markov model result by approximating a correction matrix, formulated as an integral, using a weighted sum of integrand values at specified points. GQ approximations can be made arbitrarily accurate by increasing ‘order’ of the approximation. We compared the first five orders of GQ approximation with four existing cycle correction methods (half-cycle correction, trapezoidal and Simpson’s 1/3 and 3/8 rules) across 100,000 randomly generated input parameter-sets.ResultsWe show that first-order GQ method is identical to half-cycle correction method, which is itself equivalent to trapezoidal method. The second-order GQ is identical to Simpson’s 1/3 method. The third, fourth and fifth order GQ methods are novel in this context and provide increasingly accurate approximations to the output of the continuoustime model. In our simulation study, fifth-order GQ method outperformed other existing methods in over 99.8% of simulations. Of the existing methods, Simpson’s 1/3 rule performed the best.ConclusionOur novel GQ-based approximation outperforms other cycle correction methods for time-homogeneous models. The method is easy to implement, and R code and an Excel workbook are provided as supplementary materials.
Association of D-dimer and fibrinogen magnitude with hypercoagulability by thromboelastography in severe COVID-19
Authors: Chandel Abhimanyu , Patolia Saloni , Looby Mary , Dalton Heidi J. , Bade Najeebah , Khangoora Vikramjit , Desai Mehul , Lantry James , Osborn Erik , Djurkovic Svetolik , Tang Daniel , Nathan Steven D. , King Christopher S. 
Published: July 2020

AbstractIntroductionD-dimer concentration has been used to identify candidates for intensified anticoagulant treatment for both venous thromboembolism prevention and mitigation of the microthrombotic complications associated with COVID-19. Thromboelastography (TEG) maximum amplitude (MA) has been validated as an indicator of hypercoagulability and MA ≥ 68 mm has been utilized as a marker of hypercoagulability in other conditions. We evaluated the relationship between coagulation, inflammatory, and TEG parameters in patients with COVID-19 on extracorporeal membrane oxygenation (ECMO).MethodsWe performed a single center retrospective analysis of consecutive patients that received ECMO for the treatment of COVID-19. TEG, inflammatory, and coagulation markers were compared in patients with and without thrombotic complications. Correlation tests were performed to identify the coagulation and inflammatory markers that best predict hypercoagulability as defined by an elevated TEG MA.Results168 TEGs were available in 24 patients. C-reactive protein and fibrinogen were significantly higher in patients that developed a thrombotic event versus those that did not (p=0.038 and p=0.043 respectively). D-dimer was negatively correlated with TEG MA (p<0.001) while fibrinogen was positively correlated (p<0.001). A fibrinogen > 441 mg/dL had a sensitivity of 91.2% and specificity of 85.7% for the detection of MA ≥ 68 mm.ConclusionsIn critically ill patients with COVID-19, D-dimer concentration had an inverse relationship with hypercoagulability as measured by TEG MA. D-dimer elevation may reflect severity of COVID-19 related sepsis rather than designate patients likely to benefit from anticoagulation. Fibrinogen concentration may represent a more useful marker of hypercoagulability in this population.
Interaction-based Mendelian randomization with measured and unmeasured gene-by-covariate interactions
Authors: Spiller Wes , Hartwig Fernando Pires , Sanderson Eleanor , Smith George Davey , Bowden Jack 
Published: July 2020

AbstractStudies leveraging gene-environment (GxE) interactions within Mendelian randomization (MR) analyses have prompted the emergence of two methodologies: MR-GxE and MR-GENIUS. Such methods are attractive in allowing for pleiotropic bias to be corrected when using individual instruments. Specifically, MR-GxE requires an interaction to be explicitly identified, while MR-GENIUS does not. We critically examine the assumptions of MR-GxE and MR-GENIUS, and propose sensitivity analyses to evaluate their performance. Finally, we explore the association between body mass index (BMI) and systolic blood pressure (SBP) using data from the UK Biobank. We find both approaches share similar assumptions, though differences between the approaches lend themselves to differing research settings. Where interactions are identified, MR-GxE relies on weaker assumptions and allows for further sensitivity analyses. MR-GENIUS circumvents the need to identify interactions, but relies on the MR-GxE assumptions holding globally. Through applied analyses we find evidence of a positive effect of BMI upon SBP.
A novel predictive mathematical model for COVID-19 pandemic with quarantine, contagion dynamics, and environmentally mediated transmission
Authors: Barbastefano Rafael , Carvalho Diego , Lippi Maria Clara , Pastore Dayse Haime 
Published: July 2020

ABSTRACTThis work presents an ODE model for COVID-19 named SINDROME that incorporates quarantine, contagion dynamics, and environmentally mediated transmission based on the compartments. The SINDROME model introduces a new parameter that allows environmentally mediated transmission, moving quarantined individuals to the infected compartment. We developed a gray box model with the SINDROME, and fit over 169 regions.
Estimation and correlation of sirtuin1 with Carboxy Methyl Lysine in type 2 diabetic and its microvascular complication
Authors: Mohan Sai Deepika Ram , Nagaraj Shashidhar Kurpad , Anjanappa Raveesha , Chandrappa Muninarayana 
Published: July 2020

AbstractBackgroundIncrease in Diabetes Mellitus increases incidence of its Microvascular complications such as diabetic retinopathy, diabetic kidney disease (DKD), neuropathy, stroke and cardio vascular diseases (CVD). Advanced glycation end products promotes Type 2 Diabetes to its major Microvascular complication; diabetic kidney disease or diabetic nephropathy leading to increase in expression of sirtuin1; a regulatory protein mediating deacetylation of histone proteins. In addition to diet and nutrition, environmental changes may increase incidence of disorders, one such factor considered in this study is Fluoride.ObjectiveEstimation of Sirtuin1 in type 2 diabetes mellitus and diabetic kidney disease and interpreting the outcome by diabetic profiling of patients with controls. Participants: 150 study subjects were recruited for this cross-sectional study divided into 3groups with 50 subjects in each group.MethodsDiabetic and renal profiling was carried by fully automated analyzer available in our hospital facility, eGFR was calculated, sirtuin1 and CML were measured by ELISA, serum and urine fluoride were estimated by Ion Selective Electrode.ResultsSignificant differences observed in FBS, PPBS and CML of deceased with controls. Least median of sirt1 was observed in diabetic nephropathy (36.9). Also, urine and serum fluoride levels were proportionally balanced in group 1& 2 in contrast with group 3 [0.28 (0.2-0.54) & 0.2 (0.15-0.26)].ConclusionDecrease in Sirtuin1 in group 3 may be due to chronic hyperglycemia and oxidative stress in diabetes hence, further research on large cohort may aid considering sirtuin1 as a biomarker or therapeutic target in aging disorders.
Nucleation-dependent aggregation kinetics of YeastSup35 fragment GNNQQNY
Authors: Burra Gunasekhar , Maina Mahmoud B. , Serpell Louise C. , Thakur Ashwani K. 
Published: July 2020

AbstractAn N-terminal hepta-peptide sequence of yeast prion protein Sup35 with the sequence GNNQQNY serves as an ideal model for structural understanding of amyloid assembly and kinetics. In this study, we used a reproducible solubilisation protocol that allows the generation of homogenous monomeric solution of GNNQQNY to understand the molecular details of its self-assembly mechanism. The aggregation kinetics data show that the GNNQQNY sequences follow nucleation-dependent aggregation kinetics with a critical nucleus of size ~7 monomers and that the size and efficiency of nucleation was found to be inversely related to the reaction temperature. The generated nucleus reduces the thermodynamic energy barrier by acting as a template for further self-assembly and results in highly ordered amyloid fibrils. The fibers grown at different temperatures showed similar Thioflavin T positivity, Congo red binding and β-sheet rich structures displaying a characteristic cross-β diffraction pattern. These aggregates also share morphological and structural identity with those reported earlier. The mature GNNQQNY fibers exerted no significant oxidative stress or cytotoxicity upon incubating with differentiated SHSY5Y cells. To our knowledge, this is the first study to experimentally validate previous predictions based on theoretical and molecular dynamics simulations. These findings will provide the basis for understanding the kinetics and thermodynamics of amyloid nucleation and elongation of amyloidogenic systems associated with many systemic and neurodegenerative diseases.
COCO-Search18: A Dataset for Predicting Goal-directed Attention Control
Authors: Chen Yupei , Yang Zhibo , Ahn Seoyoung , Samaras Dimitris , Hoai Minh , Zelinsky Gregory 
Published: July 2020

ABSTRACTAttention control is a basic behavioral process that has been studied for decades. The currently best models of attention control are deep networks trained on free-viewing behavior to predict bottom-up attention control—saliency. We introduce COCO-Search18, the first dataset of laboratory-qualitygoal-directed behaviorlarge enough to train deep-network models. We collected eye-movement behavior from 10 people searching for each of 18 target-object categories in 6202 natural-scene images, yielding∼300,000 search fixations. We thoroughly characterize COCO-Search18, and benchmark it using three machine-learning methods: a ResNet50 object detector, a ResNet50 trained on fixation-density maps, and an inverse-reinforcement-learning model trained on behavioral search scanpaths. Models were also trained/tested on images transformed to approximate a foveated retina, a fundamental biological constraint. These models, each having a different reliance on behavioral training, collectively comprise the new state-of-the-art in predicting goal-directed search fixations. Our expectation is that future work using COCO-Search18 will far surpass these initial efforts, finding applications in domains ranging from human-computer interactive systems that can anticipate a person’s intent and render assistance to the potentially early identification of attention-related clinical disorders (ADHD, PTSD, phobia) based on deviation from neurotypical fixation behavior.
Underground gibberellin activity: differential gibberellin response in tomato shoots and roots
Authors: Ramon Uria , Weiss David , Illouz-Eliaz Natanella 
Published: July 2020

SummaryGibberellins (GAs) are growth-promoting hormones that regulate organ growth, mainly via cell elongation. Contradicting reports leave an open question of whether GA is as important for root elongation as it is for stem elongation.Here we have addressed this question focusing on tomato (Solanum lycopersicum) primary-root elongation. We used a combination of physiological, molecular and genetic approaches to tackle this question.Tomato has three GA receptors; GID1a, GID1b1 and GID1b2. The loss of all three receptors, strongly suppressed stem elongation and leaf expansion, but had a relatively minor effect on primary root elongation. The effect of GA on cell elongation and gene-expression was much weaker in roots, than in shoots, reaching saturation at lower hormone concentrations. Our results imply that this differential response to GA in shoots and roots is caused by the lower expression of the dominant GA receptor GID1a in roots.We show that the differential activity of GA between shoots and roots affects root-to-shoot ratio, and speculate that this evolved as an adaptive mechanism to changing environments.
Changes in salt-marsh vegetation weakly affect top consumers of aquatic food webs
Authors: Denis Lafage , Alexandre Carpentier , Duhamel Sylvain , Dupuy Christine , Feunteun Eric , Lesourd Sandric , Julien Pétillon 
Published: July 2020

AbstractSalt marshes are under high, and increasing, anthropogenic pressures that have notably been reported to affect the diet of several fish species, probably resulting in nursery function alterations. Most of the previous studies in Europe were yet based on gut content analysis of fish, which can be considered a snapshot of immediate impacts of salt-marsh changes, and hardly of long-term effects of disturbances. In this study, we investigated the impact of vegetation type (resulting from both plant invasion and sheep grazing) by assessing trophic network (and especially fish diet and position) of different salt-marsh conditions. Replicated samples of basic sources (particular organic matter and microphytobenthos), dominant vegetation, potential aquatic and terrestrial prey and fish of 3 main species were taken during summer 2010 in two bays from Western France (Mont -Saint-Michel Bay and Seine Estuary) and analysed using C and N stable isotope compositions. All response variables tested (overall trophic organization, trophic niche and trophic position) provided consistent results, i.e. a dominant site effect and a weaker effect of vegetation type. Site effect was attributed to differences in anthropogenic Nitrogen inputs and tidal regime between the two bays, with more marine signatures associated with a higher frequency of flooding events. A second hypothesis is thatE. acuta, which has recently totally replaced typical salt-marsh vegetation in Mont Saint-Michel Bay strongly impacted the nursery function. The trophic status of dominant fish species was unchanged by local salt-marsh vegetation, and considered consistent with their diet, i.e. high for predatory species (the sea bassDicentrarchus labraxand the common gobyPomatoschistus microps) and lower for biofilm grazing species (the thinlip mulletChelon ramada). This study finally highlights the relevance of stable isotopes analyses for assessing long-term and integrative effects of changes in vegetation resulting from human disturbances in salt marshes.HighlightsCross-ecosystem subsidies are of high functional importance, notably in salt marshesFish are vectors of exchanges, most European studies being based on their gut contentUsing stable isotopes we analysed the effect of surrounding vegetation on food websSurprisingly we found weak vegetation and strong site effects on all metricsNitrogen inputs, site accessibility and loss of nursery function can explain this factAbstract Figure
Agricultural land use and the sustainability of social-ecological systems
Authors: Paz Diego Bengochea , Henderson Kirsten , Loreau Michel 
Published: July 2020

AbstractAgricultural land expansion and intensification, driven by human consumption of agricultural goods, are among the major threats to environmental degradation and biodiversity conservation. Land degradation can ultimately hamper agricultural production through a decrease in ecosystem services. Thus, designing viable land use strategies is a key sustainability challenge. We develop a model describing the coupled dynamics of human demography and landscape composition, while imposing a trade-off between agricultural expansion and intensification. We model land use strategies spanning from low-intensity agriculture and high land conversion rates per person to high-intensity agriculture and low land conversion rates per person; and explore their consequences on the long-term dynamics of the coupled human-land system. We seek to characterise the strategies’ viability in the long run; and understand the mechanisms that potentially lead to large-scale land degradation and population collapse due to resource scarcity. We show that the viability of land use strategies strongly depends on the land’s intrinsic recovery rate. We also find that socio-ecological collapses occur when agricultural intensification is not accompanied by a sufficient decrease in land conversion. Based on these findings we stress the dangers of naive land use planning and the importance of precautionary behaviour for land use management.
Minimizing ion competition boosts volatile metabolome coverage by secondary electrospray ionization orbitrap mass spectrometry
Authors: Lan Jiayi , Kaeslin Jérôme , Greter Giorgia , Zenobi Renato 
Published: July 2020

AbstractSecondary electrospray ionization high-resolution mass spectrometry (SESI-HR-MS) is an emerging technique for the detection of volatile metabolites. However, sensitivity and reproducibility of SESI-HRMS have limited its applications in untargeted metabolomics profiling. Ion suppression in the SESI source has been considered to be the main cause. Here, we show that besides ion suppression, ion competition in the C-trap of Orbitrap instruments is another important factor that influences sensitivity and reproducibility of SESI-MS. Instead of acquiring the full mass-to-charge ratio (m/z) range, acquisition of consecutivem/zwindows to minimize the ion competition effect allows the detection of more features.m/zwindow ranges are optimized to fill the C-trap either with an equal number of features or an equal cumulative intensity per window. Considering a balance between maximizing scanning speed and minimizing ion competition, splitting them/z= 50-500 range into 4 windows is selected for measuring human breath and bacterial culture samples on SESI-Orbitrap MS, corresponding to a duty cycle of 2.3 s at a resolution of 140’000. In a small cohort of human subjects, the proposed splitting into 4 windows allows three times more features to be detected compared to the classical fullm/zrange method.
Genome-Wide Mapping of Cisplatin Damaged Gene Loci
Authors: Qi Luyu , Luo Qun , Xu Yan , Yu Wanchen , Liu Xingkai , Zhang Yanyan , Jia Feifei , Fang Tiantian , Wang Shijun , Li Xiangjun , Zhao Yao , Wang Fuyi 
Published: July 2020

AbstractCisplatin is a DNA targeting anticancer drug, yet its damaged gene loci have remained unclear. In the present work, combining affinity isolation and high throughput sequencing, we genome-widely mapped 17729 gene loci containing platination lesions, which mainly function as enzymes, transcription regulators, transporters and kinases, and of which 445 genes account for 71% of potential gene targets for cancer therapy reported in the literature. The most related core signaling pathway, disease and tissue toxicity of 7578 genes with an enrichment fold (EFG) of >12, where EFGrefers to the ratio of total read counts of a gene detected in cells with and without cisplatin treatment, are sperm motility, cancer and hepatotoxicity with associationPvalues of < 1×10−22. Among 616 kinase genes damaged by cisplatin, 427 are protein kinases which account for 82% of putative protein kinases, suggesting that cisplatin may act as broad-spectrum protein kinase inhibitor. Western Blot assays verified that expression of 8 important protein kinase genes was significantly reduced due to cisplatin damage.SPAG9is closely related to 147 of 361 cancer diseases which the cisplatin damaged genes are associated with and was severely damaged by cisplatin. GivenSPAG9abundantly expresses JIP-4, a upstream mediator of protein kinase signaling, in testis, it may be responsible for the high sensitivity of testicular cancer to cisplatin, thus being a potential therapeutic target for precise treatment of testicular cancer. These findings provide novel insights into better understanding in molecular mechanism of anticancer activity and toxicity of cisplatin, more importantly inspire further studies in prioritizing gene targets for precise treatment of cancers.
Feeling the beat: Temporal and spatial perception of heartbeat sensations
Authors: Betka Sophie , Łukowska Marta , Silva Marta , King Joshua , Garfinkel Sarah , Critchley Hugo 
Published: July 2020

AbstractThe majority of interoceptive tasks (i.e. measuring the sensitivity to bodily signals) are based upon the heartbeat sensations perception. However, temporal perception of heartbeats varies among individuals and confidence and spatial perception of heartbeats in relation to temporal judgements have not yet been systematically investigated. This study examined the perception of heartbeat sensations in both time and spatial domains, using a multi-interval heartbeat discrimination task. The relationship between these domains was investigated, as well as the contribution of mental health conditions and cardiovascular parameters. Heartbeat sensations occurred on average ~250ms after the ECG R-wave and were more frequently sampled from the left part of the chest. Participants’ confidence in their experience of heartbeat sensations was maximal for the 0 ms interval. Interestingly, higher confidence was related to reduced dispersion of sampling locations but we found evidence toward the absence of relationship between temporal and spatial heartbeat sensations perception, using Bayesian statistics. Finally, we found evidence toward a relationship between spatial precision of heartbeat sensations and state anxiety score, which seems independent from the cardiovascular parameters. This systematic investigation of heartbeat sensations perception provides important fresh insights, informing the mechanistic understanding of the interoceptive signaling contribution to emotion, cognition and behaviour.
Atomistic Basis of Force Generation, Translocation, and Coordination in a Viral Genome Packaging Motor
Authors: Pajak Joshua , Dill Erik , Reyes-Aldrete Emilio , White Mark A. , Kelch Brian A. , Jardine Paul , Arya Gaurav , Morais Marc C. 
Published: July 2020

SummaryDouble-stranded DNA viruses package their genomes into pre-assembled capsids using virally-encoded ASCE ATPase ring motors. We present the first atomic-resolution crystal structure of a multimeric ring form of a viral dsDNA packaging motor and characterize its atomic-level dynamicsvialong timescale molecular dynamics simulations. Based on the results, we deduce an overall packaging mechanism that is driven by helical-to-planar transitions of the ring motor. These transitions are coordinated by inter-subunit interactions that regulate catalytic and force-generating events. Stepwise ATP binding to individual subunits increase their affinity for the helical DNA phosphate backbone, resulting in distortion away from the planar ring towards a helical configuration, inducing mechanical strain. Subsequent sequential hydrolysis events alleviate the accumulated mechanical strain, allowing a stepwise return of the motor to the planar conformation, translocating DNA in the process. This type of helical-to-planar mechanism could serve as a general framework for ring ATPases that exhibit burst-dwell dynamics.