Biology subjects

Song, M.

Publications and source records attributed to Song, M..

5 recordsLinked to original sources

bioRxiv2018

Adopting Literature-based Discovery on Rehabilitation Therapy Repositioning for Stroke

Stroke is a common disabling disease severely affecting the daily life of the patients. There is evidence that rehabilitation therapy can improve the movement function. However, there are no clear guidelines that identify specific, effective rehabilitation therapy schemes, and the development of new rehabilitation techniques has been fairly slow. One informatics translational approach, called ABC model in Literature-based Discovery, was used to mine an existing rehabilitation candidate which is most likely to be repositioned for stroke. As in the classic ABC model originated from Don Swanson, we built the internal links of stroke (A), assessment scales (B), rehabilitation therapies (C) in PubMed relating to upper limb function measurements for stroke patients. In the first step, with E-utility we retrieved both stroke related assessment scales and rehabilitation therapies records, and complied two datasets called Stroke_Scales and Stroke_Therapies, respectively. In the next step, we crawled all rehabilitation therapies co-occurred with the Stroke_Theapies, named as All_Therapies. Therapies that were already included in Stroke_Therapies were deleted from All_Therapies, so that the remaining therapies were the potential rehabilitation therapies, which could be repositioned for stroke after subsequent filtration by manual check. We identified the top ranked repositioning rehabilitation therapy following by subsequent clinical validation. Hand-arm bimanual intensive training (HABIT) ranked the first in our repositioning rehabilitation therapies list, with the most interaction links with Stroke_Scales. HABIT showed a significant improvement in clinical scores on assessment scales of Fugl-Meyer Assessment and Action Research Arm Test in the clinical validation on upper limb function for acute stroke patients. Based on the ABC model and clinical validation of the results, we put forward that HABIT as a promising rehabilitation therapy for stroke, which shows that the ABC model is an effective text mining approach for rehabilitation therapy repositioning. The results seem to be promoted in clinical knowledge discovery.\n\nAuthor SummaryIn the present study, we proposed a text mining approach to mining terms related to disease, rehabilitation therapy, and assessment scale from literature, with a subsequent ABC inference analysis to identify relationships of these terms across publications. The clinical validation demonstrated that our approach can be used to identify potential repositioning rehabilitation therapy strategies for stroke. Specifically, we identified a promising rehabilitation method called HABIT previously used in pediatric congenital hemiplegia. A subsequent clinical trial confirmed this as a highly promising rehabilitation therapy for stroke.

bioinformatics↗

bioRxiv2018

Fibroblast growth factor is predicted to dominate MAPK activation by pro-angiogenic factors

Angiogenesis is important in physiological and pathological conditions, as blood vessels provide nutrients and oxygen needed for tissue growth and survival. Therefore, targeting angiogenesis is a prominent strategy in both tissue engineering and cancer treatment. However, not all of the approaches to promote or inhibit angiogenesis lead to successful outcomes. Angiogenesis-based therapies primarily target pro-angiogenic factors such as vascular endothelial growth factor-A (VEGF) or fibroblast growth factor (FGF) in isolation, and there is a limited understanding of how these promoters combine together to stimulate angiogenesis. Thus, more quantitative insight is needed to understand their interactions. In this study, we have trained and validated a detailed mathematical model to quantitatively characterize the crosstalk of FGF and VEGF intracellular signaling. The model focuses on FGF- and VEGF-induced mitogen-activated protein kinase (MAPK) signaling and phosphorylation of extracellular regulated kinase (ERK), which promote cell proliferation. We apply the model to predict the dynamics of phosphorylated ERK (pERK) in response to the stimulation by FGF and VEGF individually and in combination. The model predicts that FGF plays a dominant role in promoting ERK phosphorylation, compared to VEGF. The modeling predictions show that VEGFR2 density and trafficking parameters significantly influence the level of VEGF-induced pERK. The model matches experimental data and is a framework to synthesize and quantitatively explain experimental studies. Ultimately, the model provides mechanistic insight into FGF and VEGF interactions needed to identify potential targets for pro-or anti-angiogenic therapies.

systems biology↗

bioRxiv2018

Universality of the developmental origins of diverse functional maps in the visual cortex

The primary visual cortex of higher mammals is organized into diverse functional maps of correlated topography, implying an efficient tiling of functional domains. However, no fundamental principle is available on how systematic organization of the maps could develop initially in various species. Here, we propose that diverse functional maps are seeded from a common framework of retinal afferents, and that this universality of development explains the observed topographical correlations among the maps. From the simulation of retinal ganglion cell mosaics, we successfully developed all four cortical maps observed so far. We validated our model prediction of inter-map relationships from analysis of map data in evolutionarily divergent mammalian species. Our key prediction, the hexagonal periodicity of every functional map, was validated from analysis of the map data in diverse mammalian species. Our results provide new insight into a universal mechanism for the development and evolution of the visual cortex.

neuroscience↗

bioRxiv2018

Sources of suboptimality in a minimalistic explore-exploit task

Balancing exploration and exploitation is a fundamental aspect of decision-making. It remains unknown whether people are close to optimal in striking this balance, and if not, how exactly their behavior deviates from optimality. Many existing paradigms are not ideally suited to answer this question, as they contain complexities such as non-stationary environments, stochasticity under exploitation, and reward distributions that are unknown to participants. Here, we introduce a task without such complexities, in which the optimal policy is to start off exploring and to switch to exploitation at most once in each sequence of decisions. The behavior of 49 laboratory and 143 online participants deviated both qualitatively and quantitatively from the optimal policy, even when allowing for bias and decision noise. Instead, people seem to follow a suboptimal rule in which they switch from exploration to exploitation when the highest reward so far exceeds a certain threshold. Moreover, we show that this threshold decreases approximately linearly with the proportion of the sequence that remains, suggesting a novel temporal ratio law. Finally, we find evidence for \"sequence-level\" variability which is shared across all decisions in the same sequence. Our results provide a new perspective on the explore-exploit dilemma, and emphasize the importance of examining sequence-level strategies and their variability when studying sequential decision-making.

neuroscience↗

bioRxiv2018

Heart enhancers with deeply conserved regulatory activity are established early in development

During the phylotypic period embryos from different genera show similar gene expression patterns, implying common regulatory mechanisms. To identify enhancers involved in the initial events of cardiogenesis, which occurs during the phylotypic period, we isolated early cardiac progenitor cells from zebrafish embryos and characterized 3838 open chromatin regions specific to this cell population. Of these regions, 162 overlapped with conserved non-coding elements (CNEs) that also mapped to open chromatin regions in human. Most of the zebrafish conserved open chromatin elements tested drove gene expression in the developing heart. Despite modest sequence identity, human orthologous open chromatin regions could recapitulate the spatial temporal expression patterns of the zebrafish sequence, potentially providing a basis for phylotypic gene expression patterns. Genome-wide, we discovered 5598 zebrafish-human conserved open chromatin regions, suggesting that a diverse repertoire of ancient enhancers is established prior to organogenesis and the phylotypic period.

genomics↗