bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pushing the limits of recovery in chronic stroke survivors: User perceptions of the Queen Square Upper Limb Neurorehabilitation Programme
Authors: Kelly K , Brander F , Strawson A , Ward NS , Hayward KS 
Published: January 2020

AbstractIntroductionThe Queen Square Upper Limb (QSUL) Neurorehabilitation Programme is a clinical service within the National Health Service in the United Kingdom that provides 90 hours of therapy over three weeks to stroke survivors with persistent upper limb impairment. This study aimed to explore the perceptions of participants of this programme, including clinicians, stroke survivors and carers.DesignDescriptive qualitative.SettingClinical outpatient neurorehabilitation service.ParticipantsClinicians (physiotherapists, occupational therapists, rehabilitation assistants) involved in the delivery of the QSUL Programme, as well as stroke survivors and carers who had participated in the programme were purposively sampled. Each focus group followed a series of semi-structured, open questions that were tailored to the clinical or stroke group. One independent researcher facilitated all focus groups, which were audio-recorded, transcribed verbatim and analysed by four researchers using a thematic approach to identify main themes.ResultsFour focus groups were completed: three including stroke survivors (n = 16) and carers (n =2), and one including clinicians (n = 11). The main stroke survivor themes related to psychosocial aspects of the programme (“you feel valued as an individual”), as well as the behavioural training provided (“gruelling, yet rewarding”). The main clinician themes also included psychosocial aspects of the programme (“patient driven ethos – no barriers, no rules”), and knowledge, skills and resources of clinicians (“it is more than intensity, it is complex”).ConclusionsAs an intervention, the QSUL Programme is both comprehensive and complex. The impact of participation in the programme spans psychosocial and behavioural domains from the perspectives of both the stroke survivor and clinician.Strengths and limitationsDescriptive qualitative study of the perception of users (stroke survivor, carer, clinician) engaged in the delivery of the Queen Square Upper Limb Neurorehabilitation Programme, which is run at a single centre in the United Kingdom.Focus groups were completed by a researcher independent of the programme, without the involvement of senior management to facilitate open discussion and critical reflection of the programme.This study involved a sample of users that were involved in the programme in the previous 12-months.Data coding was performed by four researchers enhancing the validity of the results.As only two carers were included in the focus groups, their experience has limited representation in the results.
Expanding cancer predisposition genes with ultra-rare cancer-exclusive human variations
Authors: Rasnic Roni , Linial Nathan , Linial Michal 
Published: January 2020

AbstractIt is estimated that up to 10% of cancer incidents are attributed to inherited genetic alterations. Despite extensive research, there are still gaps in our understanding of genetic predisposition to cancer. It was theorized that ultra-rare variants partially account for the missing heritable component. We harness the UK BioBank dataset of ∼500,000 individuals, 14% of which were diagnosed with cancer, to detect ultra-rare, possibly high-penetrance cancer predisposition variants. We report on 115 cancer-exclusive ultra-rare variations (CUVs) and nominate 26 variants with additional independent evidence as cancer predisposition variants. We conclude that population cohorts are valuable source for expanding the collection of novel cancer predisposition genes.
Dissecting the genetic overlap of education, socioeconomic status, and mental health
Authors: Wendt F. R. , Pathak G. A. , Lencz T. , Krystal J. H. , Gelernter J. , Polimanti R. 
Published: January 2020

AbstractSocioeconomic status (SES) and education (EDU) are phenotypically associated with psychiatric disorders and behavior. It remains unclear how these associations influence the genetic risk for mental health traits and EDU/SES individually. Using information from >1 million individuals, we conditioned the genetic risk for psychiatric disorders, personality traits, brain imaging phenotypes, and externalizing behaviors with genome-wide data for EDU/SES. Accounting for EDU/SES significantly affected the observed heritability of psychiatric traits ranging from 2.44% h2decrease for bipolar disorder to 29.0% h2decrease for Tourette syndrome. Neuroticism h2significantly increased by 20.23% after conditioning with SES. After EDU/SES conditioning, novel neuronal cell-types were identified for risky behavior (excitatory), major depression (inhibitory), schizophrenia (excitatory and GABAergic), and bipolar disorder (excitatory). Conditioning with EDU/SES also revealed unidirectional causality between brain morphology and mental health phenotypes. Our results indicate genetic discoveries of mental health outcomes may be limited by genetic overlap with EDU/SES.
Melanopsin Carboxy-terminus Phosphorylation Plasticity and Bulk Negative Charge, not Strict Site Specificity, Achieves Phototransduction Deactivation
Authors: Valdez-Lopez Juan C. , Gulati Sahil , Ortiz Elelbin A. , Palczewski Krzysztof , Robinson Phyllis R. 
Published: January 2020

ABSTRACTMelanopsin is a visual pigment expressed in a small subset of ganglion cells in the mammalian retina known as intrinsically photosensitive retinal ganglion cells (ipRGCs) and is implicated in regulating non-image forming functions such as circadian photoentrainment and pupil constriction and contrast sensitivity in image formation. Mouse melanopsin’s Carboxy-terminus (C-terminus) possesses 38 serine and threonine residues, which can potentially serve as phosphorylation sites for a G-protein Receptor Kinase (GRK) and be involved in the deactivation of signal transduction. Previous studies suggest that S388, T389, S391, S392, S394, S395 on the proximal region of the C-terminus of mouse melanopsin are necessary for melanopsin deactivation. We expressed a series of mouse melanopsin C-terminal mutants in HEK293 cells and using calcium imaging, and we found that the necessary cluster of six serine and threonine residues, while being critical, are insufficient for proper melanopsin deactivation. Interestingly, the additional six serine and threonine residues adjacent to the required six sites, in either proximal or distal direction, are capable of restoring wild-type deactivation of melanopsin. These findings suggest an element of plasticity in the molecular basis of melanopsin phosphorylation and deactivation. In addition, C-terminal chimeric mutants and molecular modeling studies support the idea that the initial steps of deactivation and β-arrestin binding are centered around these critical phosphorylation sites (S388-S395). This degree of functional versatility could help explain the diverse ipRGC light responses as well as non-image and image forming behaviors, even though all six sub types of ipRGCs express the same melanopsin gene OPN4.
Viral Sequence Identification in Metagenomes using Natural Language Processing Techniques
Authors: Abdelkareem Aly O. , Khalil Mahmoud I. , Elbehery Ali H. A. , Abbas Hazem M. 
Published: January 2020

ABSTRACTViral reads identification is one of the important steps in metagenomic data analysis. It shows up the diversity of the microbial communities and the functional characteristics of microorganisms. There are various tools that can identify viral reads in mixed metagenomic data using similarity and statistical tools. However, the lack of available genome diversity is a serious limitation to the existing techniques. In this work, we applied natural language processing approaches for document classification in analyzing metagenomic sequences. Text featurization is presented by treating DNA similar to natural language. These techniques reveal the importance of using the text feature extraction pipeline in sequence identification by transforming DNA base pairs into a set of characters with a term frequency and inverse document frequency techniques. Various machine learning classification algorithms are applied to viral identification tasks such as logistic regression and multi-layer perceptron. Moreover, we compared classical machine learning algorithms with VirFinder and VirNet, our deep attention model for viral reads identification on generated fragments of viruses and bacteria for benchmarking viral reads identification tools. Then, as a verification of our tool, It was applied to a simulated microbiome and virome data for tool verification and real metagenomic data of Roche 454 and Illumina for a case study.
The snowmelt niche differentiates three microbial life strategies that influence soil nitrogen availability during and after winter
Authors: Sorensen Patrick O. , Beller Harry R. , Bill Markus , Bouskill Nicholas J. , Hubbard Susan S. , Karaoz Ulas , Polussa Alexander , Steltzer Heidi , Wang Shi , Williams Kenneth H. , Wu Yuxin , Brodie Eoin L. 
Published: January 2020

AbstractSoil microbial biomass can reach its annual maximum pool size beneath the winter snowpack and is known to decline abruptly following snowmelt in seasonally snow-covered ecosystems. Observed differences in winter versus summer microbial taxonomic composition also suggests that phylogenetically conserved traits may permit winter-versus summer-adapted microorganisms to occupy distinct niches. In this study, we sought to identify archaea, bacteria, and fungi that are associated with the soil microbial bloom overwinter and the subsequent biomass collapse following snowmelt at a high-altitude watershed in central Colorado, USA. Archaea, bacteria, and fungi were categorized into three life strategies (Winter-Adapted, Snowmelt-Specialist, Spring-Adapted) based on changes in abundance during winter, the snowmelt period, and after snowmelt in spring. We calculated indices of phylogenetic relatedness (archaea and bacteria) or assigned functional attributes (fungi) to organisms within life strategies to infer whether phylogenetically conserved traits differentiate Winter-Adapted, Snowmelt-Specialist, and Spring-Adapted groups. We observed that the soil microbial bloom was correlated in time with a pulse of snowmelt infiltration, which commenced 65 days prior to soils becoming snow-free. A pulse of nitrogen (N, as nitrate) occurred after snowmelt, along with a collapse in the microbial biomass pool size, and an increased abundance of nitrifying archaea and bacteria (e.g., Thaumarchaeota, Nitrospirae). Winter- and Spring-Adapted archaea and bacteria were phylogenetically clustered, suggesting that phylogenetically conserved traits allow Winter- and Spring-Adapted archaea and bacteria to occupy distinct niches. In contrast, Snowmelt-Specialist archaea and bacteria were phylogenetically overdispersed, suggesting that the key mechanism(s) of the microbial biomass crash are likely to be density-dependent (e.g., trophic interactions, competitive exclusion) and affect organisms across a broad phylogenetic spectrum. Saprotrophic fungi were the dominant functional group across fungal life strategies, however, ectomycorrhizal fungi experienced a large increase in abundance in spring. If well-coupled plant-mycorrhizal phenology currently buffers ecosystem N losses in spring, then changes in snowmelt timing may alter ecosystem N retention potential. Overall, we observed that the snowmelt separates three distinct soil niches that are occupied by ecologically distinct groups of microorganisms. This ecological differentiation is of biogeochemical importance, particularly with respect to the mobilization of nitrogen during winter, before and after snowmelt.
Plant-pollinator interaction linkage rules are altered by agricultural intensification
Authors: Morrison Beth M. L. , Brosi Berry J. , Dirzo Rodolfo 
Published: January 2020

AbstractDetermining linkage rules that govern the formation of species interactions is a critical goal of ecologists, especially considering that biodiversity, species interactions, and the ecosystem processes they maintain are changing at rapid rate worldwide. Species traits and abundance play a role in determining plant-pollinator interactions, but we illustrate here that linkage rules of plant-pollinator interactions change with disturbance context, switching from predominantly trait-based linkage rules in undisturbed, natural habitats, to abundance-based linkage rules in intensive agricultural habitats. The transition from trait-based to abundance-based linkage rules corresponds with a decline in floral trait diversity and an increase in opportunistic interaction behavior as agricultural intensification increases. These findings suggest that agricultural intensification is changing the very rules determining the realization of interactions and the formation of communities, making it challenging to use the structure of undisturbed systems to predict interactions within disturbed communities.
Deep Learning Identifies Cardiomyocyte Nuclei in Murine Tissue with High Precision
Authors: Ali Shah R. , Nguyen Dan , Wang Brandon , Jiang Steven , Sadek Hesham A. 
Published: January 2020

ABSTRACTProper identification and annotation of cells in mammalian tissues is of paramount importance to biological research. Various approaches are currently used to identify and label cell types of interest in complex tissues. In this report, we generated an artificial intelligence (AI) deep learning model that uses image segmentation to predict cardiomyocyte nuclei in mouse heart sections without a specific cardiomyocyte nuclear label. This tool can annotate cardiomyocytes highly sensitively and specifically (AUC 0.94) using only cardiomyocyte structural protein immunostaining and a global nuclear stain. We speculate that our method is generalizable to other tissues to annotate specific cell types and organelles in a label-free way.
The relationship between the waiting time of postoperative radiotherapy and the prognosis of high grade glioma:a systemic review and meta-analysis
Authors: Li Guang-lie , Lv Shuang , Xu Ying , Zhang Hai-bo , Yan Ying 
Published: January 2020

AbstractObjective: The relationship between the waiting time of postoperative radiotherapy and the prognosis of patients with high-grade glioma is still inconclusive, and we addressed this issue through a systematic review and meta-analysis. Methods: Twenty studies published between 1975 and 2019 about waiting times (WT) of radiotherapy with high-grade glioma were retrieved for meta-analysis.The meta-analysis was performed by converting the effect sizes of different WT into regression coefficients (β) and standard error (SE) to indicate the daily impact of delay on OS. Results: A total of 8462 high-grade glioma patients were included in the 20 studies, and no correlation between WT delay and OS was found in the unadjusted model through meta-analysis (HR=1, 95%CI=0.99-1.01,p=0.962). Meta-regression was used to adjust for other prognostic factors and no clear evidence of the relationship between WT delay and OS was found. Conclusion: This meta-analysis suggests that there is no clear evidence for the effect of delayed radiotherapy on OS with high-grade glioma patients.
Inactive variants of death receptor p75NTRreduce Alzheimer’s neuropathology by interfering with APP internalization
Authors: Yi Chenju , Goh Ket Yin , Wong Lik-Wei , Tanaka Kazuhiro , Sajikumar Sreedharan , Ibáñez Carlos F. 
Published: January 2020

AbstractA prevalent model of Alzheimer’s disease (AD) pathogenesis postulates the generation of neurotoxic fragments derived from the amyloid precursor protein (APP) after its internalization to endocytic compartments. However, the molecular pathways that regulate APP internalization and intracellular trafficking in neurons are unknown. Here we report that 5xFAD mice, an animal model of AD, expressing signaling-deficient variants of the p75 neurotrophin receptor (p75NTR) show greater neuroprotection from AD neuropathology than animals lacking this receptor. p75NTRknock-in mice lacking the death domain or transmembrane Cys259showed lower levels of Aβ species, amyloid plaque burden, gliosis, mitochondrial stress and neurite dystrophy than global knock-outs. Strikingly, long-term synaptic plasticity and memory, which are completely disrupted in 5xFAD mice, were fully recovered in the knock-in mice. Mechanistically, we found that p75NTRinteracts with APP and regulates its internalization in hippocampal neurons. Inactive p75NTRvariants internalized much slower and to lower levels than wild type p75NTR, favoring non-amyloidogenic APP cleavage by reducing APP internalization and colocalization with BACE1, the critical protease for generation of neurotoxic APP fragments. These results reveal a novel pathway that directly and specifically regulates APP internalization, amyloidogenic processing and disease progression, and suggest that inhibitors targeting the p75NTRtransmembrane domain may be an effective therapeutic strategy in AD.
Study of application times gibberellic acid and 2,4-Dichlorophenoxyacetic acid in the plant regeneration from wheat haploid embryos in chromosome elimination method
Authors: Modirrousta Hamed , Khademian Raheleh , Bozorgipour Reza 
Published: January 2020

AbstractWheat is one of the most important cereals, which is very valuable in food. Haploid plants are of particular importance in plant breeding. The wheat seeds produced in the crosses between wheat and maize in the chromosome elimination method without of endosperm and are immature embryo, to prevent the abortions haploid embryos, they must have embryo rescue. Increasing production of haploid plants from produced embryos can improve production efficiency. In this study, With attention their effects gibberellic acid and 2,4-Dichlorophenoxyacetic acid on growth, cell size and cell division, Their use in the production of wheat haploid plant were studied. There was a significant difference at level 1% between the not use and use of gibberellic acid in difference times in the production of haploid from embryos, So that the most haploid plant produced in the use of gibberellic acid in the 4 days after pollination. Also, the use of 2,4-Dichlorophenoxyacetic acid in tiller maintenance liquid culture medium was evaluated at times 48 and 72 hours after pollination. There were a significant difference between these treatments at the 1% level and the most was obtained for wheat haploid plant production with application of 2,4-Dichlorophenoxyacetic acid treatment for 72 hours.Highlightproduction of haploid plants plays an important role in wheat breeding. This technique is done to get doubled haploid and absolute homozygous plants in a very short duration of time.
Chemogenetic analysis of how receptors for short chain fatty acids regulate the gut-brain axis
Authors: Barki Natasja , Bolognini Daniele , Börjesson Ulf , Jenkins Laura , Riddell John , Hughes David I. , Ulven Trond , Hudson Brian D. , Ulven Elisabeth Rexen , Dekker Niek , Tobin Andrew B. , Milligan Graeme 
Published: January 2020

AbstractThe gut-brain axis allows bi-directional communication between the enteric and central nervous systems. Short chain fatty acids (SCFAs) generated by the gut microbiota are important regulators of this interface. However, defining mechanisms by which SCFAs do so has been challenging because, amongst various roles, they co-activate both of a pair of closely related and poorly characterized G protein-coupled receptors, FFA2 and FFA3. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) can provide an important approach in defining receptor-specific functions. By screening a library of carboxylate-containing small molecules we identified 4-methoxy-3-methyl-benzoic acid (MOMBA) as a specific agonist of a DREADD variant of FFA2 which is not activated by SCFAs. Using mice engineered to replace FFA2 with this FFA2-DREADD, whilst retaining FFA3 expression, combinations of MOMBA and the now FFA3 receptor selective SCFAs defined key, but distinct, roles of FFA2 and FFA3 in each of gut transit time, secretion of entero-endocrine hormones, and communication from the gut to each of autonomic and somatic sensory ganglion cells and the spinal cord. These studies map mechanisms and signalling pathways by which each of FFA2 and FFA3 act to link the gut and the brain and provide both animal models and novel tool compounds to further explore this interface.
Differential contributions of synaptic and intrinsic inhibitory currents to speech segmentation via flexible phase-locking in neural oscillators
Authors: Pittman-Polletta Benjamin R. , Wang Yangyang , Stanley David A. , Schroeder Charles E. , Whittington Miles A. , Kopell Nancy J. 
Published: January 2020

AbstractCurrent hypotheses suggest that speech segmentation – the initial division and grouping of the speech stream into candidate phrases, syllables, and phonemes for further linguistic processing – is executed by a hierarchy of oscillators in auditory cortex. Theta (~3-12 Hz) rhythms play a key role by phase-locking to recurring acoustic features marking syllable boundaries. Reliable synchronization to quasi-rhythmic inputs, whose variable frequency can dip below cortical theta frequencies (down to ~1 Hz), requires “flexible” theta oscillators whose underlying neuronal mechanisms remain unknown. Using biophysical computational models, we found that the flexibility of phase-locking in neural oscillators depended on the types of hyperpolarizing currents that paced them. Simulated cortical theta oscillators flexibly phase-locked to slow inputs when these inputs caused both (i) spiking and (ii) the subsequent buildup of outward current sufficient to delay further spiking until the next input. The greatest flexibility in phase-locking arose from a synergistic interaction between intrinsic currents that was not replicated by synaptic currents at similar timescales. Flexibility in phase-locking enabled improved entrainment to speech input, optimal at mid-vocalic channels, which in turn supported syllabic-timescale segmentation through identification of vocalic nuclei. Our results suggest that synaptic and intrinsic inhibition contribute to frequency-restricted and -flexible phase-locking in neural oscillators, respectively. Their differential deployment may enable neural oscillators to play diverse roles, from reliable internal clocking to adaptive segmentation of quasi-regular sensory inputs like speech.Author summaryOscillatory activity in auditory cortex is believed to play an important role in auditory and speech processing. One suggested function of these rhythms is to divide the speech stream into candidate phonemes, syllables, words, and phrases, to be matched with learned linguistic templates. This requires brain rhythms to flexibly synchronize with regular acoustic features of the speech stream. How neuronal circuits implement this task remains unknown. In this study, we explored the contribution of inhibitory currents to flexible phase-locking in neuronal theta oscillators, believed to perform initial syllabic segmentation. We found that a combination of specific intrinsic inhibitory currents at multiple timescales, present in a large class of cortical neurons, enabled exceptionally flexible phase-locking, which could be used to precisely segment speech by identifying vowels at mid-syllable. This suggests that the cells exhibiting these currents are a key component in the brain’s auditory and speech processing architecture.