bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of tumour initiation, spatial and temporal progression under multiple lines of treatment
Authors: Leshchiner Ignaty , Livitz Dimitri , Gainor Justin F. , Rosebrock Daniel , Spiro Oliver , Martinez Aina , Mroz Edmund , Lin Jessica J. , Stewart Chip , Kim Jaegil , Elagina Liudmila , Bozic Ivana , Mino-Kenudson Mari , Rooney Marguerite , Ou Sai-Hong Ignatius , Wu Catherine J. , Rocco James W. , Engelman Jeffrey A. , Shaw Alice T. , Getz Gad 
Published: January 2019

AbstractDriver mutations alter cells from normal to cancer through several evolutionary epochs: premalignancy, early malignancy, subclonal diversification, metastasis and resistance to therapy. Later stages of disease can be explored through analyzing multiple samples collected longitudinally, on or between successive treatments, and finally at time of autopsy. It is also possible to study earlier stages of cancer development through probabilistic reconstruction of developmental trajectories based on mutational information preserved in the genome. Here we present a suite of tools, called Phylogic N-Dimensional with Timing (PhylogicNDT), that statistically model phylogenetic and evolutionary trajectories based on mutation and copy-number data representing samples taken at single or multiple time points. PhylogicNDT can be used to infer: (i) the order of clonal driver events (including in pre-cancerous stages); (ii) subclonal populations of cells and their phylogenetic relationships; and (iii) cell population dynamics. We demonstrate the use of PhylogicNDT by applying it to whole-exome and whole-genome data of 498 lung adenocarcinoma samples (434 previously available and 64 of newly generated data). We identify significantly different progression trajectories across subtypes of lung adenocarcinoma (EGFR mutant, KRAS mutant, fusion-driven and EGFR/KRAS wild type cancers). In addition, we study the progression of fusion-driven lung cancer in 21 patients by analyzing samples from multiple timepoints during treatment with 1st and next generation tyrosine kinase inhibitors. We characterize their subclonal diversification, dynamics, selection, and changes in mutational signatures and neoantigen load. This methodology will enable a systematic study of tumour initiation, progression and resistance across cancer types and therapies.
Identifying complex motifs in massive omics data with a variable-convolutional layer in deep neural network
Authors: Li Jing-Yi , Jin Shen , Tu Xin-Ming , Ding Yang , Gao Ge 
Published: January 2019

ABSTRACTMotif identification is among the most common and essential computational tasks for bioinformatics and genomics. Here we proposed a novel convolutional layer for deep neural network, named Variable Convolutional (vConv) layer, for effective motif identification in high-throughput omics data by learning kernel length from data adaptively. Empirical evaluations on DNA-protein binding and DNase footprinting cases well demonstrated that vConv-based networks have superior performance to their convolutional counterparts regardless of model complexity. Meanwhile, vConv could be readily integrated into multi-layer neural networks as an “in-place replacement” of canonical convolutional layer. All source codes are freely available on GitHub for academic usage.
Characterization of Dyspnea in Lung Cancer Survivors Following Curative-Intent Therapy
Authors: Ha Duc , Ries Andrew L. 
Published: January 2019

AbstractPurposeDyspnea is highly-prevalent in lung cancer survivors following curative-intent therapy. We aimed to identify clinical determinants of dyspnea and characterize its relationship with functional exercise capacity (EC).MethodsIn an analysis of data from a cross-sectional study of lung cancer survivors who completed curative-intent therapy for stage I-IIIA disease ≥1 month previously, we tested a thorough list of comorbidities, lung function, and lung cancer characteristics. We assessed dyspnea using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (LC13) and functional EC the six-minute walk. We verified results with the University of California San Diego Shortness of Breath Questionnaire (SOBQ).ResultsIn 75 participants at a median of 12 months since completing treatment, the mean (SD) LC13-Dyspnea score was 35.3 (26.2); 60% had abnormally-high dyspnea. In multivariable linear regression analyses, significant clinical determinants of dyspnea were [β (95% confidence interval)]: psychiatric illness [−20.8 (−32.4, −9.09) forNo/Yes], heart failure with reduced ejection fraction [−15.5 (−28.0, −2.97) forNo/Yes], and forced expiratory volume in 1 second [−0.28 (−0.49, −0.06) for each% predicted]. Dyspnea was an independent predictor of functional EC [−1.54 (−2.43, −0.64) for eachpoint]. These results were similar with the SOBQ.ConclusionWe identified clinical determinants of dyspnea which have pathophysiological bases. Dyspnea was independently associated with functional EC. Behavioral interventions to promote exercise in lung cancer survivors following curative-intent therapy may need to also optimize medical therapy for cardiopulmonary and/or psychiatric disease and reduce dyspnea to be effective.
Determinants of Heart Rate Recovery and Heart Rate Variability in Lung Cancer Survivors Eligible for Long-Term Cure
Authors: Ha Duc , Malhotra Atul , Ries Andrew L. , O’Neal Wesley T. , Fuster Mark M. 
Published: January 2019

AbstractBackgroundLung cancer survivors are at increased risk for autonomic dysfunction. We aimed to identify determinants of parasympathetic nervous system (PNS) function as reflected by heart rate recovery (HRR) and heart rate variability (HRV) in lung cancer survivors eligible for long-term cure.MethodsWe performed a cross-sectional study of consecutive lung cancer survivors who completed curative-intent therapy for stage I-IIIA ≥1 month previously. We tested a comprehensive list of variables related to baseline demographics, comorbidities, lung cancer characteristics, and physiological/functional measures using univariable and multivariable (MVA) linear regression analyses. We defined HRR as the difference in heart rate (HR) at 1-minute following and the end of the six-minute walk test (6MWT), and HRV the standard deviation of normal-to-normal R-R intervals (SDNN) and root-mean-square-of-successive-differences (rMSSD) from routine single 10-s electrocardiographs (ECGs).ResultsIn 69 participants, the mean (standard deviation, SD) HRR was -10.6 (6.7) beats. In MVAs, significant independent determinants of HRR [β (95% confidence interval)] were: age [0.17 (0.04, 0,30) for each year] and HR change associated with the 6MWT [0.01 (0.007, 0.02) for each beats/min. In 41 participants who had ECGs available for HRV measurements, the mean (SD) SDNN and rMSSD were 19.1 (15.6) and rMSSD 18.2 (14.6) ms, respectively. In MVAs, significant determinants of HRV were: total lung capacity [0.01 (0.00, 0.02), p=0.047 for each % predicted] and HRR [-0.04 (-0.07, -0.003) for each beat] for natural logarithm (Ln-)SDNN; and [0.01 (0.00, 0.02)] and [-0.04 (-0.07, -0.01)] for Ln-rMSSD, respectively.ConclusionsWe measured determinants of HRR and HRV in lung cancer survivors eligible for long-term cure. HRR and/or HRV may be useful as indicators to stratify patients in interventional studies aimed at improving PNS function in lung cancer survivors, including through exercise training.
Semantic richness and density effects on language production: Electrophysiological and behavioral evidence
Authors: Rabovsky Milena , Schad Daniel , Rahman Rasha Abdel 
Published: January 2019

AbstractLanguage production ultimately aims to convey meaning. Yet, words differ widely in the richness and density of their semantic representations and these differences impact conceptual and lexical processes during speech planning. Here, we replicate the recent finding that semantic richness, measured as the number of associated semantic features according to semantic feature production norms, facilitates object naming. In contrast, intercorrelational semantic feature density, measured as the degree of intercorrelation of a concept’s features, presumably resulting in the coactivation of closely related concepts, has an inhibitory influence. We replicate the behavioral effects and investigate their relative time course and electrophysiological correlates. Both the facilitatory effect of high semantic richness and the inhibitory influence of high feature density were reflected in an increased posterior positivity starting at about 250 ms, in line with previous reports of posterior positivities in paradigms employing contextual manipulations to induce semantic interference during language production. Furthermore, amplitudes at the same posterior electrode sites were positively correlated with object naming times between about 230 and 380 ms. The observed effects follow naturally from the assumption of conceptual facilitation and simultaneous lexical competition, and are difficult to explain by language production theories dismissing lexical competition.
Loud music and the specific sound stress open the blood-brain barrier: new fundamental, biomedical, and social aspects
Authors: Semyachkina-Glushkovskaya O. , Chekhonin V. , Bragin D. , Bragina O. , Vodovozova E. , Alekseeva A. , Salmin V. , Morgun A. , Malinovskaya N. , Osipova E. , Boytsova E. , Tohidpour A. , Shirokov A. , Navolokin N. , Yang Y. , Zhang C. , Feng W. , Abdurashitov A. , Ulanova M. , Shushunova N. , Khorovodov A. , Terskov A. , Shareef A. Esmat , Pavlov A. , Luo Q. , Zhu D. , Tuchin V. , Kurths. J. 
Published: January 2019

AbstractThe blood-brain barrier (BBB) poses a significant challenge for drug brain delivery. The limitation of our knowledge about the nature of BBB explains the slow progress in the therapy of brain diseases and absence of methods for drug brain delivery in the clinical practice.Here we show that BBB opens for low/high weight molecules and nanocarriers after exposure of loud music/sound of 90 dB and 100 dB (regardless its frequency) as being easily produced by MP3/MP4 players, kitchen appliances, loudspeakers at concerts. The role of sound, sound-induced stress and molecular mechanisms behind is discussed in the framework of BBB opening as an informative platform for a novel fundamental knowledge about the nature of BBB and for the development of a non-invasive brain drug delivery technology.Social aspects of music/sound-induced opening of BBB provide completely new information about noise and healthy life conditions that will stimulate new research in this field.
Comparing Task-Relevant Information Across Different Methods of Extracting Functional Connectivity
Authors: Stulz Sophie Benitez , Insabato Andrea , Deco Gustavo , Gilson Matthieu , Senden Mario 
Published: January 2019

AbstractThe concept of brain states, functionally relevant large-scale activity patterns, has become popular in neuroimaging. Not all components of such patterns are equally characteristic for each brain state, but machine learning provides a possibility for extracting and comparing the structure of brain states from functional data. However, their characterization in terms of functional connectivity measures varies widely, from cross-correlation to phase coherence, and the idea that different measures provide similar or coherent information is a common assumption made in neuroimaging. Here, we compare the brain state signatures extracted from of phase coherence, pairwise covariance, correlation, regularized covariance and regularized precision for a dataset of subjects performing five different cognitive tasks. In addition, we compare the classification performance in identifying the tasks for each connectivity measure. The measures are evaluated in their ability to discriminate the five tasks with two types of cross-validation: within-subject cross-validation, which reflects the stability of the signature over time; and between-subject cross-validation, which aims at extracting signatures that generalize across subjects. Secondly, we compare the informative features (connections or links between brain regions/areas) across measures to test the assumption that similar information is obtained about brain state signatures from different connectivity measures. In our results, the different types of cross-validation give different classification performance and emphasize that functional connectivity measures on fMRI require observation windows of sufficient duration. Furthermore, we find that informative links for the classification, meaning changes between tasks that are consistent across subjects, are entirely uncorrelated between BOLD correlations and covariances. These results indicate that the corresponding FC signature can strongly differ across FC methods used and that interpretation is subject to caution in terms of subnetworks related to a task.
A Bistable Mechanism Mediated by Integrins Controls Mechanotaxis of Leukocytes
Authors: Hornung Alexander , Sbarrato Thomas , Garcia-Seyda Nicolas , Aoun Laurene , Luo Xuan , Biarnes-Pelicot Martine , Theodoly Olivier , Valignat Marie-Pierre 
Published: January 2019

AbstractThe recruitment of leukocytes from blood vessels to inflamed zones is guided by biochemical and mechanical stimuli, with mechanisms only partially deciphered. We studied here the guidance by flow of primary human effector T lymphocytes crawling on substrates coated with ligands of integrins LFA-1 (αLβ2) and VLA-4 (α4β1), and showed that cells segregated in two populations of opposite orientation for combined adhesion. Sharp decisions of orientation were shown to rely on a bistable mechanism between LFA-1-mediated upstream and VLA-4-dominant downstream phenotypes. At the molecular level, bistability results from a differential front-rear polarization of both integrins affinity, combined with an inhibiting crosstalk of LFA-1 toward VLA-4. At the cellular level, directivity with or against the flow is mechanically mediated by the passive orientation of detached uropod or lamellipod by flow. This complete chain of logical events provides a unique mechanistic picture of a guiding mechanism, from stimuli to cell orientation.SignificanceCellular guidance is crucial to many biological functions, but the precise mechanisms remain unclear. We have analyzed here an original phenotype of flow-guided cells mimicking leukocytes crawling into the blood vessels and showed that thecontrolling parameterof cells decision to migrate upstream or downstream was therelative numberof two specific adhesion molecules, the integrins LFA-1 and VLA-4. The spatial polarisation of integrins affinity and an intermutually feedback of their activation create a bistable system where cells adhere either by their tip or their tail and orient respectively downstream or upstream. This mechanism therefore proposes a complete chain of event from stimuli to cell orientation and differs strongly from the chemotaxis paradigm because stimuli trigger no signaling.
Synaptic vesicles transiently dock to refill release sites
Authors: Kusick Grant F , Chin Morven , Raychaudhuri Sumana , Lippmann Kristina , Adula Kadidia P , Hujber Edward J , Vu Thien , Davis M Wayne , Jorgensen Erik M , Watanabe Shigeki 
Published: January 2019

AbstractSynaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must ‘dock’ to refill vacated release sites. To capture synaptic vesicle exocytosis at cultured mouse hippocampal synapses, we induced single action potentials by electrical field stimulation then subjected neurons to high-pressure freezing to examine their morphology by electron microscopy. During synchronous release, multiple vesicles can fuse at a single active zone; this multivesicular release is augmented by increasing extracellular calcium. Fusions during synchronous release are distributed throughout the active zone, whereas fusions during asynchronous release are biased toward the center of the active zone. Immediately after stimulation, the total number of docked vesicles across all synapses decreases by ∼40%. Between 8 and 14 ms, new vesicles are recruited to the plasma membrane and fully replenish the docked pool in a calcium-dependent manner, but docking of these vesicles is transient and they either undock or fuse within 100 ms. These results demonstrate that recruitment of synaptic vesicles to release sites is rapid and reversible.
Accurate Modeling of Brain Responses to Speech
Authors: Wong Daniel D.E. , Di Liberto Giovanni M. , de Cheveigné Alain 
Published: January 2019

AbstractPerceptual processes can be probed by fitting stimulus-response models that relate measured brain signals such as electroencephalography (EEG) to the stimuli that evoke them. These models have also found application for the control of devices such as hearing aids. The quality of the fit, as measured by correlation, classification, or information rate metrics, indicates the value of the model and the usefulness of the device. Models based on Canonical Correlation Analysis (CCA) achieve a quality of fit that surpasses that of commonly-used linear forward and backward models. Here, we show that their performance can be further improved using several techniques that capture the time-varying and context-dependent relationships within the data, including adaptive beamforming, CCA weight optimization, and recurrent neural networks that capture the time-varying and context-dependent relationships within the data. We demonstrate these results using a match-vs-mismatch classification paradigm, in which the classifier must decide which of two stimulus samples produced a given EEG response and which is a randomly chosen stimulus sample. This task captures the essential features of the more complex auditory attention decoding (AAD) task explored in many other studies.
Bioluminescent Multi-Characteristic Opsin for monitoring visual cortical activity upon optical stimulation
Authors: Batabyal Subrata , Gajjeraman Sivakumar , Nagai Takeharu , Wright Weldon , Mohanty Samarendra 
Published: January 2019

ABSTRACTNon-invasive detection of neural activity is important for the diagnosis of neurological diseases, evaluation of therapeutic outcomes, and collection of real-time feedback for stimulation based therapeutic approaches. In the case of vision loss, due to retinal degeneration, optic neuropathy, or enucleation of the eye, there is a need to map changes in visual cortical activity during disease progression and subsequent vision restoration by retinal, optic nerve or cortical stimulation. Existing technologies allow interrogation of neuronal circuits by both read and write activity, albeit with inherent limitations. Here, we present the development of bioluminescent multi-characteristic opsin (bMCO-11), which is comprised of a highly photosensitive ambient light-activatable domain and a Ca2+-sensitive bioluminescence reporter. The high quantum efficiency of bMCO-11 enables light activation and recording of cellular activity upon local as well as wide area optical stimulation. Furthermore, persistent Ca2+influx was achieved by bioluminescence based cyclic activation of the opsin-domain of bMCO-11 by transporting the ions only into bMCO expressing cells. This allowed us to continuously monitor visual cortical activity in wild type and retinal degenerated mice, without requiring any additional external excitation source.
PGN_0297 is an essential component of the type IX secretion system (T9SS) in Porphyromonas gingivalis: Tn‐seq analysis for exhaustive identification of T9SS‐related genes
Authors: Naito Mariko , Tominaga Takashi , Shoji Mikio , Nakayama Koji 
Published: January 2019

AbstractThe type IX secretion system (T9SS) was originally discovered in Porphyromonas gingivalis, one of the pathogenic bacteria associated with periodontal disease and is now known to be present in many members of the phylum Bacteroidetes. The T9SS secretes a number of potent virulence factors, including the highly hydrolytic proteases called gingipains, across the outer membrane in P. gingivalis. To understand the entire machinery of T9SS, an exhaustive search for T9SS‐related genes in P. gingivalis using the mariner family transposon (Tn) and Tn‐seq analysis was performed. Seven hundred and two Tn insertion sites in Tn mutants with no colony pigmentation that is associated with Lys‐gingipain (Kgp) defectiveness were determined, and it was found that the Tn was inserted in the kgp gene and 54 T9SS‐related candidate genes. Thirty‐three out of the 54 genes were already known as T9SS‐related genes. Furthermore, deletion mutant analysis of the remaining 21 genes revealed that they were not related to the T9SS. The 33 T9SS‐related genes include a gene for PGN_0297, which was found to be associated with the T9SS components PorK and PorN. A PGN_0297 gene deletion mutant was constructed, and it was found that the mutant showed no colony pigmentation, hemagglutination or gingipain activities, indicating that PGN_0297 was an essential component of the T9SS. The 33 genes did not include the six genes (gppX, omp17, porY, rfa, sigP and wzx) that were also reported as T9SS‐related genes. gppX deletion and insertion mutants were constructed, and it was found that they did not show deficiency in the T9SS.
Manager skill and portfolio size with respect to a benchmark
Authors: Bolshakov Andrei , Chincarini Ludwig B. 
Published: January 2019

AbstractInvestment managers often manage a portfolio with respect to a benchmark. Typically, they use a mean‐variance optimization framework to maximize the information ratio of their portfolio. We develop an unconventional approach to this question. Given a set of assumptions, we ask what optimal percentage of the benchmark stocks the portfolio manager should select. This optimal portfolio depends on Fisher's and Wallenius's noncentral hypergeometric distributions. We find that the optimal selectivity of a benchmark universe varies from 50% to 80%. These results are provocative, given that many enhanced index portfolio managers select a low percentage of the benchmark universe.
Plastomes of Betulaceae and phylogenetic implications
Authors: Yang Xiao‐Yue , Wang Ze‐Fu , Luo Wen‐Chun , Guo Xin‐Yi , Zhang Cai‐Hua , Liu Jian‐Quan , Ren Guang‐Peng 
Published: January 2019

AbstractBetulaceae is a well‐defined family of Fagales, including six living genera and more than 160 modern species. Species of the family have high ecological and economic value for the abundant production of wood. However, phylogenetic relationships within Betulaceae have remained partly unresolved, likely due to the lack of a sufficient number of informative sites used in previous studies. Here, we re‐investigate the Betulaceae phylogeny with whole chloroplast genomes from 24 species (17 newly assembled), representing all genera of the family. All the 24 plastomes are relatively conserved with four regions, and each genome is ∼158–161 kb long, with 111 genes. The six genera are all monophyletic in the plastome tree, whereas Ostrya Scop. is nested in the Carpinus clade in the internal transcribed spacer tree. Further incongruencies are also detected within some genera between species. Incomplete lineage sorting and/or hybrid introgression during the diversification of the family could account for such incongruencies. Our dating analysis, based on four fossils, suggests that the most recent common ancestors of the extant genera date back to the mid‐ to late Miocene, and confirms that Betulaceae started to diversify in the upper Cretaceous/early Paleocene. Our results highlight the significance of using more informative sites in resolving phylogenetic relationships. Plastome data and increased taxon sampling will help to better understand the evolutionary history of Betulaceae in the future.
The consequences of an introgression event
Authors: Barton Nicholas H. 
Published: January 2019

AbstractHanemaaijer et al. (Molecular Ecology, 27, 2018) describe the genetic consequences of the introgression of an insecticide resistance allele into a mosquito population. Linked alleles initially increased, but many of these later declined. It is hard to determine whether this decline was due to counter‐selection, rather than simply to chance.