bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic, condition-independent activity in primary motor cortex predicts corrective movement behavior
Authors: Rouse Adam G. , Schieber Marc H. , Sarma Sridevi V. 
Published: October 2018

AbstractReaching movements are known to have large condition-independent neural activity and cyclic neural dynamics. A new precision center-out task was performed by rhesus macaques to test the hypothesis that cyclic, condition-independent neural activity in the primary motor cortex (M1) occurs not only during initial reaching movements but also during subsequent corrective movements. Corrective movements were observed to be discrete with time courses and bell-shaped speed profiles similar to the initial movements. Condition-independent cyclic neural trajectories were similar and repeated for initial and each additional corrective submovement. The phase of the cyclic condition-independent neural activity predicted the time of peak movement speed more accurately than regression of instantaneous firing rate, even when the subject made multiple corrective movements. Rather than being controlled as continuations of the initial reach, a discrete cycle of motor cortex activity encodes each corrective submovement.Significance StatementDuring a precision center-out task, initial and subsequent corrective movements occur as discrete submovements with bell-shaped speed profiles. A cycle of condition-independent activity in primary motor cortex neuron populations corresponds to each submovement, such that the phase of this cyclic activity predicts the time of peak speeds—both initial and corrective. These submovements accompanied by cyclic neural activity offer important clues into how we successfully execute precise, corrective reaching movements and may have implications for optimizing control of brain-computer interfaces.
Visual cue-related activity of cells in the medial entorhinal cortex during navigation in virtual reality
Authors: Kinkhabwala Amina A. , Gu Yi , Aronov Dmitriy , Tank David W. 
Published: October 2018

AbstractDuring spatial navigation, animals use self-motion to estimate positions through path integration. However, estimation errors accumulate over time and it is unclear how they are corrected. Here we report a new cell class (“cue cell”) in mouse medial entorhinal cortex (MEC) that encoded visual cue information that could be used to correct errors in path integration. Cue cells accounted for a large fraction of unidentified MEC cells. They exhibited firing fields only near visual cues during virtual navigation and spatially stable activity during navigation in a real arena. Cue cells’ responses occurred in sequences repeated at each cue and were likely driven by visual inputs. In layers 2/3 of the MEC, cue cells formed clusters. Anatomically adjacent cue cells responded similarly to cues. These cue cell properties demonstrate that the MEC circuits contain a code representing spatial landmarks that could play a significant role in error correction during path integration.
Effective Degrees of Freedom of the Pearson’s Correlation Coefficient under Autocorrelation
Authors: Afyouni Soroosh , Smith Stephen M. , Nichols Thomas E. 
Published: October 2018

AbstractThe dependence between pairs of time series is commonly quantified by Pearson’s correlation. However, if the time series are themselves dependent (i.e. exhibit temporal autocorrelation), the effective degrees of freedom (EDF) are reduced, the standard error of the sample correlation coefficient is biased, and Fisher’s transformation fails to stabilise the variance. Since fMRI time series are notoriously autocorrelated, the issue of biased standard errors – before or after Fisher’s transformation – becomes vital in individual-level analysis of resting-state functional connectivity (rsFC) and must be addressed anytime a standardized Z-score is computed. We find that the severity of autocorrelation is highly dependent on spatial characteristics of brain regions, such as the size of regions of interest and the spatial location of those regions. We further show that the available EDF estimators make restrictive assumptions that are not supported by the data, resulting in biased rsFC inferences that lead to distorted topological descriptions of the connectome on the individual level. We propose a practical “xDF” method that accounts not only for distinct autocorrelation in each time series, but instantaneous and lagged cross-correlation. We find the xDF correction varies substantially over node pairs, indicating the limitations of global EDF corrections used previously. In addition to extensive synthetic and real data validations, we investigate the impact of this correction on rsFC measures in data from the Young Adult Human Connectome Project, showing that accounting for autocorrelation dramatically changes fundamental graph theoretical measures relative to no correction.
Multi-Center Study of Resectable Lung Lesions by Ultra-Deep Sequencing of Targeted Genes in Plasma Cell-Free DNA to Assess Nodule Malignancy and Detect Lung Cancers
Authors: Peng Muyun , Xie Yuancai , Li Xiaohua , Qian Youhui , Tu Xiaonian , Yao Xumei , Cheng Fangsheng , Xu Feiyue , Kong Deju , He Bing , Liu Chaoyu , Cao Fengjun , Yang Haoxian , He Jiankui , Yu Fenglei , Xu Chuanbo , Tian Geng 
Published: October 2018

AbstractBACKGROUNDEarly detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumor DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery.METHODSThe multi-center clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white blood cell genomic DNA (gDNA) and tumor tissue gDNA of each patient were analyzed by ultra-deep sequencing to an average of 35,000X of the coding regions of 65 lung cancer-related genes.RESULTSThe cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients is at Stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%. When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for Stage I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harbored mutations in the lung cancer patients with the largest number found in TP53 (30% plasma and 62% tumor tissue samples) and EGFR (20% and 40%, respectively).CONCLUSIONPlasma ctDNA was analyzed in lung nodule assessment and early cancer detection while an algorithm combining clinical information enhanced the test performance.
Stromal fibroblast activation and inflammation in frozen shoulder
Authors: Akbar Moeed , McLean Michael , Garcia-Melchor Emma , Crowe Lindsay AN , McMillan Paul , Fazzi Umberto G , Martin David , Arthur Angus , Reilly James H , McInnes Iain B , Millar Neal L 
Published: October 2018

AbstractIntroductionFrozen shoulder is a common, fibro-proliferative disease characterised by the insidious onset of pain and progressively restricted range of shoulder movement. Despite the prevalence of this disease, there is limited understanding of the molecular mechanisms underpinning the pathogenesis of this debilitating disease. Previous studies have identified increased myofibroblast differentiation and proliferation, immune cell influx and dysregulated cytokine production. We hypothesised that subpopulations within the stromal compartment may take on an activated phenotype, thus initiating the inflammatory processes observed in frozen shoulder. Therefore, we sought to evaluate the presence and possible pathogenic role of known stromal activation proteins in Frozen shoulder,MethodsShoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients undergoing shoulder stabilisation surgery. Stromal activation marker expression (CD248, CD146, VCAM and PDPN, FAP) was quantified using immunohistochemistry. Control and diseased fibroblasts were cultured for in vitro studies from capsule biopsies from instability and frozen shoulder surgeries, respectively. The inflammatory profile and effects of IL-1β upon diseased and control fibroblasts was assessed using ELISA, immunohistochemistry and qPCR.ResultsImmunohistochemistry demonstrated increased expression of stromal activation markers CD248, CD146, VCAM and PDPN in the frozen shoulder group compared with control (p < 0.05). Fibroblasts cultured from diseased capsule produced elevated levels of inflammatory protein (IL-6, IL-8 & CCL-20) in comparison to control fibroblasts. Exposing control fibroblasts to an inflammatory stimuli, (IL-1ß) significantly increased stromal activation marker transcript and protein expression (CD248, PDPN and VCAM).ConclusionsThese results show that stromal fibroblasts have an activated phenotype in frozen shoulder and this is associated with inflammatory cytokine dysregulation. Furthermore, it supports the hypothesis that activated stromal fibroblasts may be involved in regulating the inflammatory and fibrotic processes involved in this disease.
The Maudsley Environmental Risk Score for Psychosis
Authors: Vassos Evangelos , Sham Pak , Kempton Matthew , Trotta Antonella , Stilo Simona A. , Gayer-Anderson Charlotte , Forti Marta Di , Lewis Cathryn M , Murray Robin M , Morgan Craig 
Published: October 2018

AbstractRisk prediction algorithms have long been used in health research and practice (e.g., in prediction of cardiovascular disease, diabetes, etc.) However, similar tools have not been developed for mental health problems, despite extensive research on risk factors. For example, for psychotic disorders, attempts to sum environmental risk are rare, usually unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the total environmental risk for psychotic disorders, which can be used in research and clinical practice.We first reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis and, then, used the largest available meta-analyses to derive current best estimates of risk. We devised a method of scoring individuals based on the level of exposure to each risk factor, using odds ratios from the meta-analyses, to produce an Environmental Risk Score (ERS).Six risk factors (ethnic minority status, urbanicity, high paternal age, obstetric complications, cannabis use, and childhood adversity) were used to generate the ERS. A distribution for different levels of risk based on permuted data showed that most of population would be at low/moderate risk with a small minority at increased environmental risk for psychosis.This is the first systematic approach to develop an aggregate measure of environmental risk for psychoses. This can be used as a continuous measure of liability to disease or transformed to a relative risk. Its predictive ability will improve with the collection of additional, population specific data.
Structural basis for prodrug recognition by the SLC15 family of proton coupled peptide transporters
Authors: Minhas Gurdeep S. , Newstead Simon 
Published: October 2018

AbstractA major challenge in drug development is the optimisation of intestinal absorption and cellular uptake. A successful strategy has been to develop prodrug molecules, which hijack solute carrier (SLC) transporters for active transport into the body. The proton coupled oligopeptide transporters, PepT1 and PepT2, have been successfully targeted using this approach. Peptide transporters display a remarkable capacity to recognise a diverse library of di‐ and tri-peptides, making them extremely promiscuous and major contributors to the pharmacokinetic profile of several important drug classes, including beta-lactam antibiotics, anti-viral and antineoplastic agents. Of particular interest has been their ability to recognise amino acid and peptide-based prodrug molecules, thereby providing a rational approach to improving drug transport into the body. However, the structural basis for prodrug recognition has remained elusive. Here we present crystal structures of a prokaryotic homologue of the mammalian transporters in complex with the antiviral prodrug valacyclovir and the peptide based photodynamic therapy agent, 5-aminolevulinic acid. The valacyclovir structure reveals that prodrug recognition is mediated through both the amino acid scaffold and the ester bond, which is commonly used to link drug molecules to the carrier’s physiological ligand, whereas 5-aminolevulinic acid makes far fewer interactions compared to physiological peptides. These structures provide a unique insight into how peptide transporters interact with xenobiotic molecules and provide a template for further prodrug development.
Stochastic models of the growth dynamics of some dendritic cells
Authors: El-Said El-Nadi Khairia Khairia 
Published: October 2018

AbstractDifferent models of tumor growth are considered. Some mathematical methods are developed to analyze the dynamics of mutations enabling cells in cancer patients to metas-tize. The mathematical models consist of some stochastic dynamical systems describing tumor cells and immune effectors. It is also considered a method to find the ideal outcome of some treatments. Some different types of dendritic cells are considered. The obtained results will help to find some suitable treatments,which can be successful in returning an aggressive tumor to its passive,non-immune evading state. The principle goal of this paper is to find ways to treat the cancer tumors before they can reach an advanced stage devel-opmen.AMS Subject Classifications92B05, 37C45.
Neural dynamics at rest associated with patterns of ongoing thought
Authors: Karapanagiotidis Theodoros , Vidaurre Diego , Quinn Andrew J. , Vatansever Deniz , Poerio Giulia L. , Jefferies Elizabeth , Margulies Daniel S. , Nichols Thomas E. , Woolrich Mark W. , Smallwood Jonathan 
Published: October 2018

AbstractConscious experience is dynamic, and its fluidity is particularly marked when attention is not occupied by events in the external world and our minds are free to wander. Our study used measures of neural function, and advanced analyses techniques to examine how unconstrained neural state transitions relate to patterns of ongoing experience. Neural activity was recorded during wakeful rest using functional magnetic resonance imaging and Hidden Markov modelling identified recurrent patterns of brain activity constituting functional dynamic brain states. Individuals making more frequent transitions between states subsequently described experiences highlighting problem solving and lacking unpleasant intrusive features. Frequent switching between states also predicted better health and well-being as assessed by questionnaire. These data provide evidence that the fluidity with which individuals shift through dynamic neural states has an impact on the nature of ongoing thought, and suggest that greater flexibility at rest is an important indicator of a healthy mind.
Validation of a low-cost, carbon dioxide-based cryoablation system for percutaneous tumor ablation
Authors: Surtees Bailey , Young Sean , Hu Yixin , Wang Guannan , McChesney Evelyn , Kuroki Grace , Acree Pascal , Thomas Serena , Blair Tara , Rastogi Shivam , Kraitchman Dara L. , Weiss Clifford , Sukumar Saraswati , Harvey Susan C. , Durr Nicholas J 
Published: October 2018

AbstractBreast cancer rates are rising in low- and middle-income countries (LMICs), yet there is a lack of accessible and cost-effective treatment. As a result, the cancer burden and death rates are highest in LMICs. In an effort to meet this need, our work presents the design and feasibility of a low-cost cryoablation system using widely-available carbon dioxide as the only consumable. This system uses an 8-gauge outer-diameter needle and Joule-Thomson expansion to percutaneously necrose tissue with cryoablation. Bench top experiments characterized temperature dynamics in ultrasound gel demonstrated that isotherms greater than 2 cm were formed. Further, this system was applied to mammary tumors in anin vivorat model and necrosis was verified by histopathology. Finally, freezing capacity under a large heat load was assessed with anin vivoporcine study, where volumes of necrosis greater than 1.5 cm in diameter confirmed by histopathology were induced in a highly perfused liver after two 7-minute freeze cycles. These results demonstrate the feasibility of a carbon-dioxide based cryoablation system for improving solid tumor treatment options in resource-constrained environments.
Genome-wide association analysis of excessive daytime sleepiness identifies 42 loci that suggest phenotypic subgroups
Authors: Wang Heming , Lane Jacqueline M , Jones Samuel E , Dashti Hassan S , Ollila Hanna , Wood Andrew R , van Hees Vincent T. , Brumpton Ben , Winsvold Bendik S , Kantojärvi Katri , Cade Brian E , Sofer Tamar , Song Yanwei , Patel Krunal , Anderson Simon G , Bechtold David A , Bowden Jack , Emsley Richard , Kyle Simon D , Little Max A , Loudon Andrew S , Scheer Frank AJL , Purcell Shaun M , Richmond Rebecca C , Spiegelhalder Kai , Tyrrell Jessica , Zhu Xiaofeng , Kristiansson Kati , Sulkava Sonja , Paunio Tiina , Hveem Kristian , Nielsen Jonas B , Willer Cristen J , Zwart John-Anker , Strand Linn B , Frayling Timothy M , Ray David , Lawlor Deborah A , Rutter Martin K , Weedon Michael N , Redline Susan , Saxena Richa 
Published: October 2018

AbstractExcessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. We identified 42 loci for self-reported EDS in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirmed the aggregate effect of a genetic risk score of 42 SNPs on EDS in independent Scandinavian cohorts and on other sleep disorders (restless leg syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). Strong genetic correlations were also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing. EDS variants clustered into two predominant composite phenotypes - sleep propensity and sleep fragmentation - with the former showing stronger evidence for enriched expression in central nervous system tissues, suggesting two unique mechanistic pathways. Mendelian randomization analysis indicated that higher BMI is causally associated with EDS risk, but EDS does not appear to causally influence BMI.
scBFA: modeling detection patterns to mitigate technical noise in large-scale single cell genomics data
Authors: Li Ruoxin , Quon Gerald 
Published: October 2018

AbstractTechnical variation in feature measurements such as gene expression and locus accessibility is a key challenge of large-scale single cell genomic datasets. We show that this technical variation in both scRNA-seq and scATAC-seq datasets can be mitigated by performing analysis on feature detection patterns alone and ignoring feature quantification measurements. This result holds when datasets have low detection noise relative to quantification noise. We demonstrate state-of-the-art performance of detection pattern models using our new framework, scBFA, for both cell type identification and trajectory inference. Performance gains can also be realized in one line of R code in existing pipelines.
In situ observation of phase changes of a silica-supported cobalt catalyst for the Fischer–Tropsch process by the development of a synchrotron-compatible in situ/operando powder X-ray diffraction cell
Authors: Hoffman Adam S. , Singh Joseph A. , Bent Stacey F. , Bare Simon R. 
Published: October 2018

In situ characterization of catalysts gives direct insight into the working state of the material. Here, the design and performance characteristics of a universal in situ synchrotron-compatible X-ray diffraction cell capable of operation at high temperature and high pressure, 1373 K, and 35 bar, respectively, are reported. Its performance is demonstrated by characterizing a cobalt-based catalyst used in a prototypical high-pressure catalytic reaction, the Fischer–Tropsch synthesis, using X-ray diffraction. Cobalt nanoparticles supported on silica were studied in situ during Fischer–Tropsch catalysis using syngas, H2 and CO, at 723 K and 20 bar. Post reaction, the Co nanoparticles were carburized at elevated pressure, demonstrating an increased rate of carburization compared with atmospheric studies.
Constrained control of helicopter vibration to reduce motion blur
Authors: Oktay Tugrul , Celik Harun , Turkmen Ilke 
Published: October 2018

Purpose
The purpose of this paper is to examine the success of constrained control on reducing motion blur which occurs as a result of helicopter vibration.

Design/methodology/approach
Constrained controllers are designed to reduce the motion blur on images taken by helicopter. Helicopter vibrations under tight and soft constrained controllers are modeled and added to images to show the performance of controllers on reducing blur.

Findings
The blur caused by vibration can be reduced via constrained control of helicopter.

Research limitations/implications
The motion of camera is modeled and assumed same as the motion of helicopter. In model of exposing image, image noise is neglected, and blur is considered as the only distorting effect on image.

Practical implications
Tighter constrained controllers can be implemented to take higher quality images by helicopters.

Social implications
Recently, aerial vehicles are widely used for aerial photography. Images taken by helicopters mostly suffer from motion blur. Reducing motion blur can provide users to take higher quality images by helicopters.

Originality/value
Helicopter control is performed to reduce motion blur on image for the first time. A control-oriented and physic-based model of helicopter is benefited. Helicopter vibration which causes motion blur is modeled as blur kernel to see the effect of helicopter vibration on taken images. Tight and soft constrained controllers are designed and compared to denote their performance in reducing motion blur. It is proved that images taken by helicopter can be prevented from motion blur by controlling helicopter tightly.