bluuebunny/crossref_metadata_2025_split huggingface dataset:
A transferrable and interpretable multiple instance learning model for microsatellite instability prediction based on histopathology images
Authors: Cao Rui , Yang Fan , Ma Si-Cong , Liu Li , Li Yan , Wu De-Hua , Zhao Yu , Wang Tong-Xin , Lu Wei-Jia , Cai Wei-Jing , Zhu Hong-Bo , Guo Xue-Jun , Lu Yu-Wen , Kuang Jun-Jie , Huan Wen-Jing , Tang Wei-Min , Huang Junzhou , Yao Jianhua , Dong Zhong-Yi 
Published: March 2020

ABSTRACTBackgroundMicrosatellite instability (MSI) is a negative prognostic factor for colorectal cancer (CRC) and can be used as a predictor of success for immunotherapy in pan-cancer. However, current MSI identification methods are not available for all patients. We propose an ensemble multiple instance learning (MIL)-based deep learning model to predict MSI status directly from histopathology images.DesignTwo cohorts of patients were collected, including 429 from The Cancer Genome Atlas (TCGA-COAD) and 785 from a self-collected Asian data set (Asian-CRC). The initial model was developed and validated in TCGA-COAD, and then generalized in Asian-CRC through transfer learning. The pathological signatures extracted from the model are associated with genotypes for model interpretation.ResultsA model called Ensembled Patch Likelihood Aggregation (EPLA) was developed in the TCGA-COAD training set based on two consecutive stages: patch-level prediction and WSI-level prediction. The EPLA model achieved an area-under-the -curve (AUC) of 0.8848 in the TCGA-COAD test set, which outperformed the state-of-the-art approach, and an AUC of 0.8504 in the Asian-CRC after transfer learning. Furthermore, the five pathological imaging signatures identified using the model are associated with genomic and transcriptomic profiles, which makes the MIL model interpretable. Results show that our model recognizes pathological signatures related to mutation burden, DNA repair pathways, and immunity.ConclusionOur MIL-based deep learning model can effectively predict MSI from histopathology images and are transferable to a new patient cohort. The interpretability of our model by association with genomic and transcriptomic biomarkers lays the foundation for prospective clinical research.
Parasitism of trees by marmosets (Primates: Callitrichidae) enhance tree turnover
Authors: Souza-Alves João Pedro , Barbosa Guilherme V. , Hilário Renato Richard 
Published: March 2020

AbstractWe tested if gouging byCallithrix jacchusaffects tree survival. The proportion of dead gouged trees in forest fragments was higher than the proportion of dead non-gouged trees, with larger effect on smaller trees. The number of holes did not affect tree survival. Parasitism of trees by marmosets may enhance forest turnover.
Intracranial recordings demonstrate medial temporal lobe engagement in visual search in humans
Authors: Slama S. J. Katarina , Jimenez Richard , Saha Sujayam , King-Stephens David , Laxer Kenneth D. , Weber Peter B. , Endestad Tor , Larsson Pål G. , Solbakk Anne-Kristin , Lin Jack J. , Knight Robert T. 
Published: March 2020

AbstractVisual search is a fundamental human behavior, which has been proposed to include two component processes: inefficient search (Search) and efficient search (Pop-out). According to extant research, these two processes map onto two separable neural systems located in the frontal and parietal association cortices. In the present study, we use intracranial recordings from 23 participants to delineate the neural correlates of Search and Pop-out with an unprecedented combination of spatiotemporal resolution and coverage across cortical and subcortical structures. First, we demonstrate a role for the medial temporal lobe in visual search, on par with engagement in frontal and parietal association cortex. Second, we show a gradient of increasing engagement over anatomical space from dorsal to ventral lateral frontal cortex. Third, we confirm previous work demonstrating nearly complete overlap in neural engagement across cortical regions in Search and Pop-out. We further demonstrate Pop-out selectivity manifesting as activity increase in Pop-out as compared to Search in a distributed set of sites including frontal cortex. This result is at odds with the view that Pop-out is implemented in low-level visual cortex or parietal cortex alone. Finally, we affirm a central role for the right lateral frontal cortex in Search.
COVID-19 Epidemic Outside China: 34 Founders and Exponential Growth
Authors: Li Yi , Liang Meng , Yin Xianhong , Liu Xiaoyu , Hao Meng , Hu Zixin , Wang Yi , Jin Li 
Published: March 2020

SummaryBackgroundIn December 2019, pneumonia infected with a novel coronavirus burst in Wuhan, China. Now the situation is almost controlled in China but is worse outside China. We aimed to build a mathematical model to capture the global trend of epidemics outside China.MethodsIn this retrospective, outside-China diagnosis number reported from Jan 21 to Feb 28, 2020 was downloaded from WHO website. We develop a simple regression model on these numbers:where Ntis the total diagnosed patient till theith day, t=1 at Feb 1.FindingsBased on this model, we estimate that there have been about 34 unobserved founder patients at the beginning of spread outside China. The global trend is approximately exponential, with the rate of 10 folds every 19 days.Research in contextEvidence before this studyIn December 2019, pneumonia infected with a novel coronavirus burst in Wuhan, China. Now the situation is almost controlled in China but is worse outside China. Now there are 4,691 patients across 51 countries and territories outside China. We searched PubMed and the China National Knowledge Infrastructure database for articles published up to Feb 28, 2020, using the keywords “COVID”, “novel coronavirus”, “2019-nCoV” or “2019 novel coronavirus”. No published work about the global trend of epidemics outside China could be identified.Added value of this studyWe built a simple “log-plus” linear model to capture the global trend of epidemics outside China. We estimate that there have been about 34 unobserved founder patients at the beginning of spread outside China. The global trend is approximately exponential, with the rate of 10 folds every 19 days.Implications of all the available evidenceWith the limited number of data points and the complexity of the real situation, a straightforward model is expected to work better. Our model suggests that the COVID-19 disease follows an approximate exponential growth model stably at the very beginning. We predict that the number of confirmed patients outside China will increase ten folds in every 19 days without strong intervention by applying our model. Powerful actions on public health should be taken to combat this epidemic all over the world.
Interspecific Hybrids Show a Reduced Adaptive Potential Under DNA Damaging Conditions
Authors: Bautista Carla , Marsit Souhir , Landry Christian R 
Published: March 2020

AbstractHybridization may increase the probability of adaptation to extreme stresses. This advantage could be caused by an increased genome plasticity in hybrids, which could accelerate the search for adaptive mutations. High ultraviolet (UV) radiation is a particular challenge in terms of adaptation because it affects the viability of organisms by directly damaging DNA, while also challenging future generations by increasing mutation rate. Here we test if hybridization accelerates adaptive evolution in response to DNA damage, using yeast as a model. We exposed 180 populations of hybrids between species (Saccharomyces cerevisiaeandSaccharomyces paradoxus) and their parental strains to UV mimetic and control conditions for approximately 100 generations. Although we found that adaptation occurs in both hybrids and parents, hybrids achieved a lower rate of adaptation, contrary to our expectations. Adaptation to DNA damage conditions comes with a large and similar cost for parents and hybrids, suggesting that this cost is not responsible for the lower adaptability of hybrids. We suggest that the lower adaptive potential of hybrids in this condition may result from the interaction between DNA damage and the inherent genetic instability of hybrids.
Automatic encoding of a view-centered background image in the macaque temporal lobe
Authors: Chen He , Naya Yuji 
Published: March 2020

AbstractPerceptual processing along the ventral visual pathway to the hippocampus is hypothesized to be substantiated by signal transformation from retinotopic space to relational space, which represents interrelations among constituent visual elements. However, our visual perception necessarily reflects the first person’s perspective based on the retinotopic space. To investigate this two-facedness of visual perception, we compared neural activities in the temporal lobe (anterior inferotemporal cortex, perirhinal and parahippocampal cortices, and hippocampus) between when monkeys gazed on an object and when they fixated on the screen center with an object in their peripheral vision. We found that in addition to the spatially invariant object signal, the temporal lobe areas automatically represent a large-scale background image, which specify the subject’s viewing location. These results suggest that a combination of two distinct visual signals on relational space and retinotopic space may provide the first person’s perspective serving for perception and presumably subsequent episodic memory.
Spatial organization of the kelp microbiome at micron scales
Authors: Ramirez-Puebla S. Tabita , Weigel Brooke L. , Jack Loretha , Schlundt Cathleen , Pfister Catherine A. , Mark Welch Jessica L. 
Published: March 2020

AbstractMacroalgae are colonized by complex and diverse microbial communities that are distinct from those on inert substrates, suggesting intimate symbioses that likely play key roles in both macroalgal and bacterial biology. Canopy-forming kelp fix teragrams of carbon per year in coastal kelp forest ecosystems, yet little is known about the structure and development of their associated microbial communities. We characterized the spatial organization of bacterial communities on blades of the canopy-forming kelpNereocystis luetkeanausing fluorescencein situhybridization and spectral imaging with a probe set combining phylum, class and genus-level probes to target >90% of the microbial community. We show that kelp blades host a dense microbial biofilm, generally less than 20 μm thick, in which disparate microbial taxa live in close contact with one another. The biofilm is spatially differentiated, with tightly clustered cells of the dominant symbiontGranulosicoccus sp. (Gammaproteobacteria) close to the kelp surface and filamentousBacteroidetesand Alphaproteobacteria relatively more abundant near the biofilm-seawater interface. Further, a community rich inBacteroidetescolonized the interior of kelp tissues. Microbial community structure and cell density increased along the length of the kelp blade, from sparse microbial colonization of newly produced tissues at the meristematic base of the blade to an abundant microbial biofilm on older tissues at the blade tip. Finally, kelp from a declining population hosted fewer microbial cells compared to kelp from a stable population, indicating that biofilms are characteristic of health and that biofilm loss may be related to the condition of the host.ImportanceThe microbial community coating the surfaces of macroalgae may play a key but underexplored role both in the biology of the macroalgal host and in the biogeochemistry of the coastal ocean. We show that photosynthetic blades of the canopy-forming kelpNereocystis luetkeanahost a complex microbial biofilm that is both dense and spatially differentiated. Microbes of different taxa are in intimate cell-to-cell contact with one another; microbial cells invade the interior of kelp cells as well as cover their external surfaces; and a subset of the surface microbiota projects into the water column. These results highlight the potential for metabolic interactions between key members of the kelp microbiome as well as between microbes and their host. The dense layer of microbes coating the surface of the kelp blade is well-positioned to mediate interactions between the host and surrounding organisms and to modulate the chemistry of the surrounding water column.
Development of locomotion in low water exposure using sturgeon
Authors: Asano-Hoshino Anshin. , Tanaka Hideyuki. , Nakakura Takashi. , Tsuji Toshiaki. , Mizukami Takuo. 
Published: March 2020

AbstractThe evolution of early land vertebrates from aquatic forms of life was a biological milestone. The transition to land was accompanied with expectedly challenging physiological and morphological evolutionary hurdles. So far, fossil records have provided substantial information on the origin of quadrupedal locomotion. However, fossil evidence alone is insufficient to understand how the soft-tissue-dependent motor functions and locomotion were acquired and developed. In the present study, we focus on locomotion of the sturgeon, an extant primitive fish, as a new experimental model, to investigate behavioural plasticity. Their locomotion in low-water-level conditions was similar to an escape response in water, the C-start escape response, which is used by most fish and amphibian juveniles to avoid predation. Sturgeons were also found to have mastered rolling-over in response to low water levels, resulting in the improvement of their trunk-twisting action. Sturgeons acquired an efficient shift in their centroid, thereby improving their mobility. We hypothesise that the escape response triggered by environmental hazards drove the development of locomotion, which was accompanied by a variety of behaviours.
Revised annotation and characterization of novelAedes albopictusmiRNAs and their potential functions in dengue virus infection
Authors: Azlan Azali , Yunus Muhammad Amir , Azzam Ghows 
Published: March 2020

AbstractThe Asian tiger mosquito,Aedes albopictus(Ae. albopictus), is a highly invasive species that transmit several arboviruses including dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV). Although several studies have identified microRNAs (miRNAs) inAe. albopictus, it is crucial to extend and improve current annotations with the newly improved genome assembly, and the increase number of small RNA-sequencing data. We combined our high-depth sequence data and 26 public datasets to re-annotateAe. albopictusmiRNAs, and found a total of 110 novel mature miRNAs. We discovered that the expression of novel miRNAs was lower than known miRNAs. Furthermore, compared to known miRNAs, novel miRNAs are prone to be expressed in stage-specific manner. Upon DENV infection, a total of 59 novel miRNAs were differentially expressed, and target prediction analysis revealed that miRNA-target genes were involved in lipid metabolism and protein processing in endoplasmic reticulum. Taken together, miRNA annotation profile provided here is the most comprehensive to date, and we believed that this will facilitate future research in understanding virus-host interactions particularly on the role of miRNAs.
Drug-induced resistance in micrometastases: analysis of spatio-temporal cell lineages
Authors: Pérez-Velázquez Judith , Rejniak Katarzyna A. 
Published: March 2020

AbstractResistance to anti-cancer drugs is a major cause of treatment failure. While several intracellular mechanisms of resistance have been postulated, the role of extrinsic factors in the development of resistance in individual tumor cells is still not fully understood. Here we used a hybrid agent-based model to investigate how sensitive tumor cells develop drug resistance in the heterogeneous tumor microenvironment. We characterized the spatio-temporal evolution of lineages of the resistant cells and examined how resistance at the single-cell level contributes to the overall tumor resistance. We also developed new methods to track tumor cell adaptation, to trace cell viability trajectories and to examine the three-dimensional spatio-temporal lineage trees. Our findings indicate that drug-induced resistance can result from cells adaptation to the changes in drug distribution. Two modes of cell adaptation were identified that coincide with microenvironmental niches—areas sheltered by cell micro-communities (protectorates) or regions with limited drug penetration (refuga or sanctuaries). We also recognized that certain cells gave rise to lineages of resistant cells (precursors of resistance) and pinpointed three temporal periods and spatial locations at which such cells emerged. This supports the hypothesis that tumor micrometastases do not need to harbor cell populations with pre-existing resistance, but that individual tumor cells can adapt and develop resistance induced by the drug during the treatment.
Meta-analysis of the effects of sleep deprivation on depression in patients and animals
Authors: Hu Baiqi , Ye Mengfei , Feng Dan , Ying Jianghua , Mou Tingting , Luo Fangyi , Lv Tingting , Jiang Liya , Qian Chao , Ding Zhinan , Yu Chaoyang , Gao Hui , Zhang Jian , Liu Zheng 
Published: March 2020

ObjectiveResearch on the antidepressant effects of sleep deprivation (SD) is lagging and has not produced completely uniform results in humans and animals. The present study aimed to reassess the effect of SD on patients and animals by meta-analysis based on updated research.MethodsWe searched PubMed, Embase and Cochrane Library for articles since the first relevant literature published up to June 10th, 2019. Data on sample characteristics, features of SD, and tests for depression were extracted.ResultsFourteen articles were included, eight on humans and six on animals. We found that when the duration of SD in patients was 7–14 days, it reflected antidepression [-1.52 (−2.07, −0.97); I2=19.6%]. In animals, the results of sucrose consumption experiments showed that SD has depressogenic effects [-1.06 (−1.63, −0.49); I2=81.1%], while the results of forced swimming experiments showed that SD treated depression [-1.17 (−2.19, −0.16); I2=80.1%], regardless of the duration of sleep deprivation.ConclusionSD can be an effective antidepressant measure when the duration is 7–14 days in patients. In animal studies, SD has shown more antidepressant effects when measured by forced swimming experiments, whereas using sucrose consumption tests had the effect of worsening depression.
Enrichment of disease-associated genes in cortical areas defined by transcriptome-based parcellation
Authors: Gregor Gryglewski , Matej Murgaš , Paul Michenthaler , Manfred Klöbl , Bruce Reed Murray , Jakob Unterholzner , Rupert Lanzenberger 
Published: March 2020

AbstractThe parcellation of the cerebral cortex serves the investigation of the emergence of uniquely human brain functions and disorders. We employed hierarchical clustering based on comprehensive transcriptomic data of the human cortex in order to delineate areas with distinct gene expression profiles. These profiles were analyzed for the enrichment of gene sets associated with brain disorders by genome-wide studies (GWAS) and expert curation. This suggested new roles of specific cortical areas in psychiatric, neurodegenerative, congenital and other neurological disorders while reproducing some well-established links for movement disorders and dementias. GWAS-derived gene sets for psychiatric disorders exhibited similar enrichment patterns in the posterior fusiform gyrus and inferior parietal lobule driven by pleiotropic genes. This implies that the effects of risk variants shared between neuropsychiatric disorders might converge in these areas. For several diseases, specific genes were highlighted, which may aid the discovery of novel disease mechanisms and urgently needed treatments.
Streptococcus pyogenesM1T1 variants activate caspase-1 and induce an inflammatory neutrophil phenotype
Authors: Williams Jonathan G. , Ly Diane , Geraghty Nicholas J. , McArthur Jason D. , Vyas Heema K. N. , Gorman Jody , Tsatsaronis James A. , Sluyter Ronald , Sanderson-Smith Martina L. 
Published: March 2020

SummaryInvasive infections due to Group AStreptococcus(GAS) advance rapidly causing tissue degradation and unregulated inflammation. Neutrophils are the primary immune cells that respond to GAS. The neutrophil response to GAS was characterised in response to two M1T1 isolates; 5448 and animal passaged variant 5448AP. Neutrophil co-incubation with 5448AP allowed proliferation of GAS while it also lowered the production of reactive oxygen species by neutrophils when compared with 5448. Infection with both strains invoked neutrophil death, however apoptosis was reduced in response to 5448AP. Both strains induced neutrophil caspase-1 activation and caspase-4 expressionin vitro, with caspase-1 activation detectedin vivo. Thus, GAS infection of neutrophils corresponds to increased caspase-1 activity and caspase-4 expression, consistent with inflammasome activation and pyroptosis. GAS infections that promote an inflammatory neutrophil phenotype may contribute to increased inflammation yet ineffective bacterial eradication, contributing to the speed and severity of invasive GAS infections.
Transferrin-dependent crosstalk between the intestinal tract and commensal microbes contributes for immune tolerance
Authors: Tang Xiaopeng , Fang Mingqian , Xu Kuanhong , Cheng Ruomei , Wang Gan , Liao Zhiyi , Zhang Zhiye , Mwangi James , Lu Qiumin , Lai Ren 
Published: March 2020

SummaryCrosstalks between gastrointestinal tract and commensal microbes regulate immune tolerance and maintain host intestinal homeostasis. However, molecular events that regulate the crosstalks remain poorly understood. Here, we show that microbial products (lipopolysaccharide, lipoteichoic acid and DNA) up-regulate host transferrin, an iron supplier of commensal bacteria, to induce host’s immune tolerance by negatively regulating toll-like receptor (TLR) signaling. Transferrin level in germ-free and broad-spectrum antibiotics-treated mice is much less than that in normal mice. Transferrin is found to silence TLR signaling complex by directly interacting with CD14, a co-receptor of many TLRs. Transferrin knock-down impaired host tolerogenic responses as well as broad-spectrum antibiotics treatment. Our findings reveal that commensal bacteria up-regulate and beneficially use host transferrin as a negative regulator of TLR signaling to shape host immunity and contribute for intestinal tolerance.