bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of Conservative Therapy in COVID-19 Patients Presenting with Gastrointestinal Bleeding
Authors: Shalimar DM , Vaishnav Manas , Elhence Anshuman , Kumar Ramesh , Mohta Srikant , Palle Chandan , Kumar Peeyush , Ranjan Mukesh , Vajpai Tanmay , Prasad Shubham , Yegurla Jatin , Dhooria Anugrah , Banyal Vikas , Agarwal Samagra , Bansal Rajat , Bhattacharjee Sulagna , Aggarwal Richa , Soni Kapil Dev , Rudravaram Swetha , Singh Ashutosh Kumar , Altaf Irfan , Choudekar Avinash , Mahapatra Soumya Jagannath , Gunjan Deepak , Kedia Saurabh , Makharia Govind , Trikha Anjan , Garg Pramod , Saraya Anoop 
Published: August 2020

AbstractBackground/ObjectiveThere is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with COVID-19 amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19.
MethodsIn this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22 April to 22 July 2020, were included.ResultsThe mean age of patients was 45.8±12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis-21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay.ConclusionConservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient’s condition, response to treatment, resources and the risks involved, on a case to case basis.
Patterns of population genomic diversity in the invasive Japanese knotweed species complex
Authors: VanWallendael Acer , Alvarez Mariano , Franks Steven J. 
Published: August 2020

AbstractPremiseInvasive species are expected to experience a reduction in genetic diversity due to founder effects, which should limit their ability to adapt to new habitats. Still, many invasive species achieve widespread distributions and dense populations. This paradox of invasions could potentially be overcome through multiple introductions or hybridization, both of which increase genetic diversity. We conducted a population genomics study of Japanese knotweed (Reynoutria japonica), which is a polyploid, clonally reproducing invasive species that has been notoriously successful worldwide despite supposedly low genetic diversity.MethodsWe used Genotyping-by-Sequencing to collect 12,912 SNP markers from 88 samples collected at 38 locations across North America for the species complex. We used non-alignment based k-mer hashing analysis in addition to traditional population genetic analyses to account for the challenges of genotyping polyploids.ResultsGenotypes conformed to three genetic clusters, likely representing Japanese knotweed, Giant knotweed, and hybrid Bohemian knotweed. We found that, contrary to previous findings, the Japanese knotweed cluster had substantial genetic diversity, though it had no apparent genetic structure across the landscape. In contrast, Giant knotweed and hybrids showed distinct population groups. We did not find evidence of Isolation-by-Distance in the species complex, likely reflecting the stochastic introduction history of this species complex. Among species, we found no correlations between SNPs and several temperature- and precipitation-based climatic variables.ConclusionsThe results indicate that clonal invasive species can show substantial genetic diversity and can be successful at colonizing a variety of habitats without showing evidence of local adaptation or genetic structure.
Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate
Authors: Bangaru Sandhya , Ozorowski Gabriel , Turner Hannah L. , Antanasijevic Aleksandar , Huang Deli , Wang Xiaoning , Torres Jonathan L. , Diedrich Jolene K. , Tian Jing-Hui , Portnoff Alyse D. , Patel Nita , Massare Michael J. , Yates John R. , Nemazee David , Paulson James C. , Glenn Greg , Smith Gale , Ward Andrew B. 
Published: August 2020

AbstractVaccine efforts against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. Here, we performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared to published spike ectodomain structures. Interestingly, we also observed novel interactions between the spike trimers allowing formation of higher order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.
Viromes outperform total metagenomes in revealing the spatiotemporal patterns of agricultural soil viral communities
Authors: Santos-Medellin Christian , Zinke Laura A. , ter Horst Anneliek M. , Gelardi Danielle L. , Parikh Sanjai J. , Emerson Joanne B. 
Published: August 2020

AbstractViruses are abundant yet understudied members of soil environments that influence terrestrial biogeochemical cycles. Here, we characterized the dsDNA viral diversity in biochar-amended agricultural soils at the pre-planting and harvesting stages of a tomato growing season via paired total metagenomes and viromes. Size fractionation prior to DNA extraction reduced sources of non-viral DNA in viromes, enabling the recovery of a vaster richness of viral populations (vOTUs), greater viral taxonomic diversity, broader range of predicted hosts, and better access to the rare virosphere, relative to total metagenomes, which tended to recover only the most persistent and abundant vOTUs. Of 2,961 detected vOTUs, 2,684 were recovered exclusively from viromes, while only three were recovered from total metagenomes alone. Both viral and microbial communities differed significantly over time, suggesting a coupled response to rhizosphere recruitment processes and nitrogen amendments. Viral communities alone were also structured along a spatial gradient. Overall, our results highlight the utility of soil viromics and reveal similarities between viral and microbial community dynamics throughout the tomato growing season yet suggest a partial decoupling of the processes driving their spatial distributions, potentially due to differences in dispersal, decay rates, and/or sensitivities to soil heterogeneity.
Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease
Authors: Inglés-Prieto Álvaro , Furthmann Nikolas , Crossman Samuel , Hoyer Nina , Petersen Meike , Zheden Vanessa , Biebl Julia , Reichhart Eva , György Attila , Siekhaus Daria , Soba Peter , Winklhofer Konstanze F. , Janovjak Harald 
Published: August 2020

AbstractOptogenetics has been harnessed to shed new mechanistic light on current therapies and to develop future treatment strategies. This has been to date achieved by the correction of electrical signals in neuronal cells and neural circuits that are affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and thereby may modify progression of degenerative disorders, has never been demonstrated in an animal disease model. Here, we reengineered the human andDrosophila melanogasterREarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRETviathe PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to overcome limitations of current strategies towards a spatio-temporal regulation of tissue repair.Significance StatementThe death of physiologically important cell populations underlies of a wide range of degenerative disorders, including Parkinson’s disease (PD). Two major strategies to counter cell degeneration, soluble growth factor injection and growth factor gene therapy, can lead to the undesired activation of bystander cells and non-natural permanent signaling responses. Here, we employed optogenetics to deliver cell type-specific pro-survival signals in a genetic model of PD. InDrosophilaand human cells exhibiting loss of the PINK1 kinase, akin to autosomal recessive PD, we efficiently suppressed disease phenotypes using a light-activated tyrosine kinase receptor. This work demonstrates a spatio-temporally precise strategy to interfere with degeneration and may open new avenues towards tissue repair in disease models.
A novel method for tri-clustering dynamic functional network connectivity (dFNC) identifies significant schizophrenia effects across multiple states in distinct subgroups of individuals
Authors: Rahaman Md Abdur , Damaraju Eswar , Turner Jessica A. , van Erp Theo G.M. , Mathalon Daniel , Vaidya Jatin , Muller Bryon , Pearlson Godfrey , Calhoun Vince D. 
Published: August 2020

AbstractBackgroundBrain imaging data collected from individuals are highly complex with unique variation; however, such variation is typically ignored in approaches that focus on group averages or even supervised prediction. State-of-the-art methods for analyzing dynamic functional network connectivity (dFNC) subdivide the entire time course into several (possibly overlapping) connectivity states (i.e., sliding window clusters). Though, such an approach does not factor in the homogeneity of underlying data and may end up with a less meaningful subgrouping of the dataset.MethodsDynamic-N-way tri-clustering (dNTiC) incorporates a homogeneity benchmark to approximate clusters that provide a more apples-to-apples comparison between groups within analogous subsets of time-space and subjects. dNTiC sorts the dFNC states by maximizing similarity across individuals and minimizing variance among the pairs of components within a state.ResultsResulting tri-clusters show significant differences between schizophrenia (SZ) and healthy control (HC) in distinct brain regions. Compared to HC, SZ in most tri-clusters show hypoconnectivity (low positive) among subcortical, default mode, cognitive control but hyper-connectivity (high positive) between sensory networks. In tri-cluster 3, HC subjects show significantly stronger connectivity among sensory networks and anticorrelation between subcortical and sensory networks compared to SZ. Results also provide statistically significant difference in reoccurrence time between SZ and HC subjects for two distinct dFNC states.ConclusionsOutcomes emphasize the utility of the proposed method for characterizing and leveraging variance within high-dimensional data to enhance the interpretability and sensitivity of measurements in the study of a heterogeneous disorder like schizophrenia and in unconstrained experimental conditions such as resting fMRI.
Modeling Parent-Specific Genetic Nurture in Families with Missing Parental Genotypes: Application to Birthweight and BMI
Authors: Tubbs Justin D. , Hwang Liang-Dar , Luong Justin , Evans David M. , Sham Pak C. 
Published: August 2020

AbstractDisaggregation and estimation of genetic effects from offspring and parents has long been of interest to statistical geneticists. Recently, technical and methodological advances have made the genome-wide and loci-specific estimation of direct offspring and parental genetic nurture effects more possible. However, unbiased estimation using these methods requires datasets where both parents and at least one child have been genotyped, which are relatively scarce. Our group has recently developed a method and accompanying software (IMPISH; Hwang et al., 2020) which is able to impute missing parental genotypes from observed data on sibships and estimate their effects on an offspring phenotype conditional on the effects of genetic transmission. However, this method is unable to disentangle maternal and paternal effects, which may differ in magnitude and direction. Here, we introduce an extension to the original IMPISH routine which takes advantage of all available nuclear families to impute parent-specific missing genotypes and obtain asymptotically unbiased estimates of genetic effects on offspring phenotypes. We apply this this method to data from related individuals in the UK Biobank, showing concordance with previous estimates of maternal genetic effects on offspring birthweight. We also conduct the first GWAS jointly estimating offspring-, maternal-, and paternal-specific genetic effects on body mass index.
The mutational load in natural populations is significantly affected by high primary rates of retroposition
Authors: Zhang Wenyu , Xie Chen , Ullrich Kristian , Zhang Yong E. , Tautz Diethard 
Published: August 2020

AbstractGene retroposition is known to contribute to patterns of gene evolution and adaptations. However, possible negative effects of gene retroposition remain largely unexplored, since most previous studies have focussed on between-species comparisons where negatively selected copies are mostly not observed, as they are quickly lost from the populations. Here, we show for natural house mouse populations that the primary rate of retroposition is orders of magnitude higher than previously thought. Comparisons with SNP distribution patterns in the same populations show that most retroposition events are deleterious. Transcriptomic profiling analysis shows that new retroposed copies become easily subject to transcription and have an influence on the expression level of their parental genes, especially when transcribed in the antisense direction. Our results imply that the impact of retroposition on the mutational load in natural populations has been highly underestimated, which has also implications for strategies of disease allele detection in humans.Significance statementThe phenomenon or retroposition (re-integration of reverse transcribed RNA into the genome), has been well studied in comparisons between genomes and has been identified as a source of evolutionary innovation. However, the negative effects of retroposition have been overlooked so far. Our study makes use of a unique population genomic dataset from natural mouse populations. It shows that the retroposition rate is magnitudes higher than previously suspected. We show that most of the newly transposed retrocopies have a deleterious impact through modifying the expression of their parental genes. In humans, this effect is expected to cause disease alleles and we propose that genetic screening needs to take into account the search for newly transposed retrocopies.
Increased oscillatory power in a computational model of the olfactory bulb due to synaptic degeneration
Authors: Berry J. Kendall , Cox Daniel 
Published: August 2020

AbstractSeveral neurodegenerative diseases impact the olfactory system, and in particular the olfactory bulb, early in disease progression. One mechanism by which damage occurs is via synaptic dysfunction. Here, we implement a computational model of the olfactory bulb and investigate the effect of weakened connection weights on network oscillatory behavior. Olfactory bulb network activity can be modeled by a system of equations that describes a set of coupled nonlinear oscillators. In this modeling framework, we propagate damage to synaptic weights using several strategies, varying from localized to global. Damage propagated in a dispersed or spreading manner leads to greater oscillatory power at moderate levels of damage. This increase arises from a higher average level of mitral cell activity due to a shift in the balance between excitation and inhibition. That this shift leads to greater oscillations critically depends on the nonlinearity of the activation function. Linearized analysis of the network dynamics predicts when this shift leads to loss of oscillatory activity. We thus demonstrate one potential mechanism involved in the increased gamma oscillations seen in some animal models of Alzheimer’s disease and highlight the potential that pathological olfactory bulb behavior presents as an early biomarker of disease.
Prime editing primarily induces undesired outcomes in mice
Authors: Aida Tomomi , Wilde Jonathan J. , Yang Lixin , Hou Yuanyuan , Li Mengqi , Xu Dongdong , Lin Jianbang , Qi Peimin , Lu Zhonghua , Feng Guoping 
Published: August 2020

SummaryGenome editing has transformed biomedical science, but is still unpredictable and often induces undesired outcomes. Prime editing (PE) is a promising new approach due to its proposed flexibility and ability to avoid unwanted indels. Here, we show highly efficient PE-mediated genome editing in mammalian zygotes. Utilizing chemically modified guideRNAs, PE efficiently introduced 10 targeted modifications including substitutions, deletions, and insertions across 6 genes in mouse embryos. However, we unexpectedly observed a high frequency of undesired outcomes such as large deletions and found that these occurred more often than pure intended edits across all of the edits/genes. We show that undesired outcomes result from the double-nicking PE3 strategy, but that omission of the second nick largely ablates PE function. However, sequential double-nicking with PE3b, which is only applicable to a fraction of edits, eliminated undesired outcomes. Overall, our findings demonstrate the promising potential of PE for predictable, flexible, and highly efficientin vivogenome editing, but highlight the need for improved variations of PE before it is ready for widespread use.
Molecular motion and tridimensional nanoscale localization of kindlin control integrin activation in focal adhesions
Authors: Orré Thomas , Karatas Zeynep , Kastberger Birgit , Cabriel Clément , Böttcher Ralph T. , Lévêque-Fort Sandrine , Sibarita Jean-Baptiste , Fässler Reinhard , Wehrle-Haller Bernhard , Rossier Olivier , Giannone Grégory 
Published: August 2020

AbstractFocal adhesions (FAs) initiate chemical and mechanical signals involved in cell polarity, migration, proliferation and differentiation. Super-resolution microscopy revealed that FAs are organized at the nanoscale into functional layers from the lower plasma membrane to the upper actin cytoskeleton. Yet, how FAs proteins are guided into specific nano-layers to promote interaction with given targets is unknown. Using single protein tracking, super-resolution microscopy and functional assays, we linked the molecular behavior and tridimensional nanoscale localization of kindlin with its function in integrin activation inside FAs. We show that immobilization of integrins in FAs depends on interaction with kindlin. Unlike talin, kindlin displayed free diffusion along the plasma membrane outside and inside FAs. We demonstrate that the kindlin Pleckstrin Homology domain promotes membrane diffusion and localization to the membrane-proximal integrin nano-layer, necessary for kindlin enrichment and function in FAs. Using kindlin-deficient cells, we show that kindlin membrane localization and diffusion are crucial for integrin activation during cell adhesion and spreading. Thus, kindlin uses a different route than talin to reach and activate integrins, providing a possible molecular basis for their complementarity during integrin activation.
Moving toward versus away from another: how body motion direction changes the representation of bodies and actions in the visual cortex
Authors: Bellot Emmanuelle , Abassi Etienne , Papeo Liuba 
Published: August 2020

AbstractRepresenting multiple agents and their mutual relations is a prerequisite to understand social events. Using functional MRI on human adults, we show that visual areas dedicated to body-form and body-motion perception contribute to processing social events, by holding the representation of multiple moving bodies and encoding the spatial relations between them. In particular, seeing animations of human bodies facing and moving toward (vs. away from) each other, increased neural activity in the body-selective cortex (extrastriate body area -EBA) and posterior superior temporal sulcus for biological-motion perception (bm-pSTS). In those areas, representation of body postures and movements, as well as of the overall scene, was more accurate for facing-body (vs. non-facing body) stimuli. Effective connectivity analysis with Dynamic Causal Modeling revealed increased coupling between EBA and bm-pSTS during perception of facing-body stimuli. The attunement of human vision to multiple-body scenes involving perceptual cues of interaction such as face-to-face positioning and approaching behaviour, was further supported by the participants’ better performance in a match-to-sample task with facing-bodyvs. non-facing body stimuli. Thus, visuo-spatial cues of interaction in multiple-person scenarios affect the perceptual representation of body and body motion and, by promoting functional integration, streamline the process from body perception to action representation.