bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kidney Transplantation After Rescue Allocation—the Eurotransplant Experience: A Retrospective Multicenter Outcome Analysis
Authors: Assfalg Volker , Miller Gregor , Stocker Felix , van Meel Marieke , Groenevelt Tiny , Tieken Ineke , Ankerst Donna , Renders Lutz , Novotny Alexander , Hartmann Daniel , Jell Alissa , Rahmel Axel , Wahba Roger , Mühlfeld Anja , Bouts Antonia , Ysebaert Dirk , Globke Brigitta , Jacobs-Tulleneers-Thevissen Daniel , Piros László , Stippel Dirk , Heller Katharina , Eisenberger Ute , van Laecke Steven , Weimer Rolf , Rosenkranz Alexander R. , Berger Stefan , Fischer Lutz , Kliem Volker , Vondran Florian , Sester Urban , Schneeberger Stefan , Harth Ana , Kuypers Dirk , Függer Reinhold , Arnol Miha , Christiaans Maarten , Weinmann-Menke Julia , Krüger Bernd , Hilbrands Luuk , Banas Bernhard , Hakenberg Oliver , Minnee Robert , Schwenger Vedat , Heyne Nils , van Zuilen Arjan , Reindl-Schwaighofer Roman , Lopau Kai , Hüser Norbert , Heemann Uwe 
Published: October 2021

Background.
At Eurotransplant (ET), kidneys are transferred to “rescue allocation” (RA), whenever the standard allocation (SA) algorithms Eurotransplant Kidney Allocation System (ETKAS) and Eurotransplant Senior Program (ESP) fail. We analyzed the outcome of RA.

Methods.
Retrospective patient clinical and demographic characteristics association analyses were performed with graft outcomes for 2422 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25 481 after SA from 71 centers across all ET countries from 2006 to 2018.

Results.
Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP versus ETKAS (2.7% versus 10.4%). RA recipients and donors were older compared with SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary nonfunction was comparable. Among ETKAS recipients, HLA matching was more favorable in SA (mean 3.7 versus 2.5). In multivariate modeling, the incidence of graft loss in ETKAS recipients was reduced in RA compared with SA (subdistribution hazard ratio, 0.80; 95% confidence interval [0.70-0.91], P < 0.001), whereas other outcomes (mortality, death with functioning graft (DwFG)) were not significantly different. None of the 3 outcomes were significantly different when comparing RA with SA within the ESP program.

Conclusions.
Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration.
Oral and intranasal Ad5 SARS-CoV-2 vaccines decrease disease and viral transmission in a golden hamster model
Authors: Langel Stephanie N. , Johnson Susan , Martinez Clarissa I. , Tedjakusuma Sarah N. , Peinovich Nadine , Dora Emery G. , Kuehl Philip J. , Irshad Hammad , Barrett Edward G. , Werts Adam , Tucker Sean N 
Published: October 2021

AbstractTransmission-blocking strategies that slow the spread of SARS-CoV-2 and protect against COVID-19 are needed. We have developed a shelf-stable, orally-delivered Ad5-vectored SARS-CoV-2 vaccine candidate that expresses the spike protein. Here we demonstrated that oral and intranasal SARS-CoV-2 vaccination of this candidate protected against disease in index hamsters, and decreased aerosol transmission to unvaccinated, naïve hamsters. We confirmed that mucosally-vaccinated hamsters had robust antibody responses. We then induced a post-vaccination infection by inoculating vaccinated index hamsters with SARS-CoV-2. Oral and IN-vaccinated hamsters had decreased viral RNA and infectious virus in the nose and lungs and experienced less lung pathology compared to mock-vaccinated hamsters post challenge. Naive hamsters exposed in a unidirectional air flow chamber to mucosally-vaccinated, SARS-CoV-2-infected hamsters had lower nasal swab viral RNA and exhibited less clinical symptoms of disease than control animals. Our data demonstrate that oral immunization is a viable strategy to decrease SARS-CoV-2 disease and aerosol transmission.
Circulating proteins to predict adverse COVID-19 outcomes
Authors: Su Chen-Yang , Zhou Sirui , Gonzalez-Kozlova Edgar , Butler-Laporte Guillaume , Brunet-Ratnasingham Elsa , Nakanishi Tomoko , Jeon Wonseok , Morrison David , Laurent Laetitia , Afilalo Jonathan , Afilalo Marc , Henry Danielle , Chen Yiheng , Carrasco-Zanini Julia , Farjoun Yossi , Pietzner Maik , Kimchi Nofar , Afrasiabi Zaman , Rezk Nardin , Bouab Meriem , Petitjean Louis , Guzman Charlotte , Xue Xiaoqing , Tselios Chris , Vulesevic Branka , Adeleye Olumide , Abdullah Tala , Almamlouk Noor , Moussa Yara , DeLuca Chantal , Duggan Naomi , Schurr Erwin , Brassard Nathalie , Durand Madeleine , Del Valle Diane Marie , Thompson Ryan , Cedillo Mario A. , Schadt Eric , Nie Kai , Simons Nicole W , Mouskas Konstantinos , Zaki Nicolas , Patel Manishkumar , Xie Hui , Harris Jocelyn , Marvin Robert , Cheng Esther , Tuballes Kevin , Argueta Kimberly , Scott Ieisha ,   The Mount Sinai COVID-19 Biobank Team, Greenwood Celia M T , Paterson Clare , Hinterberg Michael A. , Langenberg Claudia , Forgetta Vincenzo , Pineau Joelle , Mooser Vincent , Marron Thomas , Beckmann Noam , Kenigsberg Ephraim , Kim-schulze Seunghee , Charney Alexander W. , Gnjatic Sacha , Kaufmann Daniel E. , Merad Miriam , Richards J Brent 
Published: October 2021

AbstractPredicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4,701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict adverse COVID-19 outcomes in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4,701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different adverse COVID-19 outcomes were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of adverse COVID-19 outcomes. Further research is needed to understand how to incorporate protein measurement into clinical care.
Impact of Diabetes Status on Immunogenicity of Trivalent Inactivated Influenza Vaccine in Older Adults
Authors: Spencer Sarah , Chung Jessie R. , Belongia Edward A. , Sundaram Maria , Meece Jennifer , Coleman Laura A. , Zimmerman Richard , Nowalk Mary Patricia , Moehling Krissy K. , Ross Ted , Carter Chalise E. , Shay David , Levine Min , Liepkalns Justine , Kim Jin Hyang , Sambhara Suryaprakash , Thompson Mark , Flannery Brendan 
Published: October 2021

AbstractIndividuals with type 2 diabetes mellitus experience high rates of influenza virus infection and complications. We compared the magnitude and duration of serologic response to trivalent influenza vaccine in adults aged 50-80 with and without type 2 diabetes mellitus. Serologic response to influenza vaccination was similar in both groups: greater fold-increases in antibody titer occurred among individuals with lower pre-vaccination antibody titers. Waning of antibody titers was not influenced by diabetes status.
Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae
Authors: Thompson Ryan C. , Simons Nicole W. , Wilkins Lillian , Cheng Esther , Del Valle Diane Marie , Hoffman Gabriel E. , Fennessy Brian , Mouskas Konstantinos , Francoeur Nancy J. , Johnson Jessica S. , Lepow Lauren , Berichel Jessica Le , Chang Christie , Beckmann Aviva G. , Wang Ying-chih , Nie Kai , Zaki Nicholas , Tuballes Kevin , Barcessat Vanessa , Cedillo Mario A. , Huckins Laura , Roussos Panagiotis , Marron Thomas U. ,   The Mount Sinai COVID-19 Biobank Team, Glicksberg Benjamin S. , Nadkarni Girish , Gonzalez-Kozlova Edgar , Kim-Schulze Seunghee , Sebra Robert , Merad Miriam , Gnjatic Sacha , Schadt Eric E. , Charney Alexander W. , Beckmann Noam D. 
Published: October 2021

Summary ParagraphTwo years into the SARS-CoV-2 pandemic, the post-acute sequelae of infection are compounding the global health crisis. Often debilitating, these sequelae are clinically heterogeneous and of unknown molecular etiology. Here, a transcriptome-wide investigation of this new condition was performed in a large cohort of acutely infected patients followed clinically into the post-acute period. Gene expression signatures of post-acute sequelae were already present in whole blood during the acute phase of infection, with both innate and adaptive immune cells involved. Plasma cells stood out as driving at least two distinct clusters of sequelae, one largely dependent on circulating antibodies against the SARS-CoV-2 spike protein and the other antibody-independent. Altogether, multiple etiologies of post-acute sequelae were found concomitant with SARS-CoV-2 infection, directly linking the emergence of these sequelae with the host response to the virus.
Reactivating Memories from a Mathematical Task over a Period of Sleep
Authors: Bassard Adrianna M. , Paller Ken A. 
Published: October 2021

AbstractSleep, especially slow-wave sleep (SWS), has been found to facilitate memory consolidation for many types of learning. Mathematical learning, however, has seldom been examined in this context. Solving multiplication problems involves multiple steps before problems can be mastered or answers memorized, and thus it can depend on both skill learning and fact learning. Here we aimed to test the hypothesis that memory reactivation during sleep contributes to multiplication learning. To do so, we used a technique known as targeted memory reactivation (TMR), or the pairing of newly learned information with specific stimuli that are later presented during sleep. With TMR, specific memories can be reactivated over a period of sleep without disrupting ongoing sleep. We applied TMR during an afternoon nap to reactivate half of the multiplication problems that had previously been practiced. Results showed no effect of TMR on response time or accuracy of multiplication problem solving. Because these results were unexpected, we also used a variation of this paradigm to examine results in subjects who remained awake. Comparisons between the wake and sleep groups showed no difference in response time or accuracy in either the initial test or the final test. Although neither TMR nor sleep differentially influenced multiplication performance, correlational analysis provided some clues about mathematical problem solving and sleep. On the basis of these findings, even though they did not provide convincing support for our hypotheses, we suggest future experiments that could help produce a better understanding of the relevance of sleep and memory reactivation for this type of learning.
Proteoglycan Clusters as a Site of Coordinated, Multi-Dendritic Plasticity
Authors: Chelini Gabriele , Durning Peter , O’Donovan Sinead , Klengel Torsten , Balasco Luigi , Berciu Cristina , Boyer-Boiteau Anne , Bozzi Yuri , McCullumsmith Robert , Ressler Kerry J. , Berretta Sabina 
Published: October 2021

AbstractExperience-dependent learning depends on synaptic plasticity. While plasticity in individual synapses has been extensively investigated, the mechanisms underlying coordinated changes across sets of synapses on multiple dendrites, likely needed to encode effective adaptations to a salient stimulus, are not well understood. The extracellular matrix is uniquely well suited to fulfill this function, as rapid glia-driven remodeling of its local composition powerfully impact synaptic plasticity. We show that extracellular matrix microenvironments, named CS6 clusters, dynamically form around several dendrites in response to sensory stimuli in coincidence to stimulus-driven synaptic plasticity. CS6 clusters, formed by glia-dependent secretion of extracellular matrix components surrounding sets of adjacent dendrites, may represent a novel structure supporting coordinated synaptic plasticity.One Sentence SummaryExtracellular matrix clusters form microenvironments for coordinated multi-dendrite synaptic plasticity.
Cooperative breeding and the emergence of multilevel societies in birds
Authors: Camerlenghi Ettore , McQueen Alexandra , Delhey Kaspar , Cook Carly N. , Kingma Sjouke A. , Farine Damien R. , Peters Anne 
Published: October 2021

ABSTRACTMultilevel societies (MLSs), where social levels are hierarchically nested within each other, are considered one of the most complex forms of animal societies. Although thought to mainly occur in mammals, it is suggested that MLSs could be under-detected in birds. Here we propose that the emergence of MLSs could be common in cooperatively breeding birds, as both systems are favoured by similar ecological and social drivers. We first investigate this proposition by systematically comparing evidence for multilevel social structure in cooperative and non-cooperative birds in Australia and New Zealand, global hotspots for cooperative breeding. We then analyse non-breeding social networks of cooperatively breeding superb fairy-wrens (Malurus cyaneus) to reveal their structured multilevel society, with three hierarchical social levels that are stable across years. Our results confirm recent predictions that MLSs are likely to be widespread in birds and suggest that these societies could be particularly common in cooperatively breeding birds.
Novel microRNAs targeting NMDA receptor subunits in animal models of schizophrenia
Authors: Gunasekaran Sowmya , Jacob Reena S. , Omkumar Ramakrishnapillai V. 
Published: October 2021

AbstractN-methyl-D-aspartate receptors (NMDAR) are downregulated in schizophrenia possibly through microRNAs (miRNAs) that are differentially expressed in this condition. We screened the miRNAs that are altered in schizophrenia against the targets, Grin2A and Grin2B subunits of NMDAR using bioinformatic tools. Among the predicted miRNAs some interacted with the 3’-UTR sequences of Grin2A (miR-296, miR-148b, miR-129-2, miR-137) and Grin2B (miR-296, miR-148b, miR-129-2, miR-223) in dual luciferase assays. This was supported by downregulation of the GluN2B protein in primary hippocampal neurons upon overexpressing Grin2B targeting miRNAs. In two models of schizophrenia-pharmacological MK-801 model and neurodevelopmental methylazoxymethanol acetate (MAM) model which showed cognitive deficits - protein levels of GluN2A and GluN2B were downregulated but their transcript levels were upregulated. MiR-296-3p, miR-148b-5p and miR-137 levels showed upregulation in both models which could have interacted with Grin2A/Grin2B transcripts resulting in translational arrest. In MAM model, reciprocal changes in the expression of the 3p and 5p forms of miR-148b and miR-137 were observed. Expression of neuregulin 1 (NRG1), BDNF and CaMKIIα, genes implicated in schizophrenia, were also altered in these models. This is the first report of downregulation of GluN2A and GluN2B by miR-296, miR-148b and miR-129-2. Mining miRNAs regulating NMDA receptors might give insights into the pathophysiology of this disorder, providing avenues in therapeutics.
B.1.617.3 SARS CoV-2 spike E156G/Δ157-158 mutations contribute to reduced neutralization sensitivity and increased infectivity
Authors: Mishra Tarun , Joshi Garima , Kumar Atul , Dalavi Rishikesh , Pandey Pankaj , Shukla Sanjeev , Mishra Ram Kumar , Chande Ajit 
Published: October 2021

AbstractSARS CoV-2 variants raise significant concerns due to their ability to cause vaccine breakthrough infections. Here, we sequence-characterized the spike gene, isolated from a breakthrough infection, that corresponded to B.1.617.3 lineage. Delineating the functional impact of spike mutations using reporter pseudoviruses (PV) revealed that N-terminal domain (NTD)-specific E156G/Δ157-158 contributed to increased infectivity and reduced sensitivity to ChAdOx1 nCoV-19 vaccine (Covishield™)-elicited neutralizing antibodies. A six-nucleotide deletion (467-472) in the spike coding region introduced this change in the NTD. We confirmed the presence of E156G/Δ157-158 in the RT-PCR-positive cases concurrently screened, in addition to other circulating spike (S1) mutations like T19R, T95I, L452R, E484Q, and D614G. Notably, E156G/Δ157-158 was present in more than 85% of the sequences reported from the USA, UK, and India in August 2021. The spike PV bearing combination of E156G/Δ157-158 and L452R further promoted infectivity and conferred immune evasion. Additionally, increased cell-to-cell fusion was observed when spike harbored E156G/Δ157-158, L452R, and E484Q, suggesting a combinatorial effect of these mutations. Notwithstanding, the plasma from a recovered individual robustly inhibited mutant spike PV, indicating the increased breadth of neutralization post-recovery. Our data highlights the importance of spike NTD-specific changes in determining infectivity and immune escape of variants.
DLPFC controls the rapid neural response to visual threat: An ERP and rTMS study
Authors: Cinq-Mars Justine , Blumenthal Anna , Grund Alessa , Hétu Sébastien , Blanchette Isabelle 
Published: October 2021

AbstractIndividuals are faster at detecting threatening stimuli than neutral stimuli. While generally considered a rapid bottom-up response, this threat superiority effect is also modulated by top-down mechanisms known to rely on the dorsolateral prefrontal cortex (DLPFC). What remains unclear is whether the response is modulated only at later stages of processing, or whether rapid attention to threat itself is controlled in a top-down manner. To test this, we used repetitive transcranial magnetic stimulation (rTMS) to inhibit activity in the DLPFC, and measured EEG to index the immediate neural response to threat. Participants attended two sessions where they performed a visual search task with threatening or neutral targets. Prior to this, they received 15 minutes of 1 Hz inhibitory or sham rTMS targeting the right DLPFC. We measured the impact of rTMS on the P1, a rapid visually-evoked potential that is modulated by attention. We found that threatening targets increased the amplitude of the P1 in the sham condition, but inhibition of the DLPFC abolished this increase. These results suggest that the neural signature of rapid attentional detection of threat, even at its earliest stage, is influenced in a top-down fashion by the right DLPFC.
Automatic Metadata Generation for Fish Specimen Image Collections
Authors: Pepper Joel , Greenberg Jane , Bakiş Yasin , Wang Xiaojun , Bart Henry , Breen David 
Published: October 2021

AbstractMetadata are key descriptors of research data, particularly for researchers seeking to apply machine learning (ML) to the vast collections of digitized specimens. Unfortunately, the available metadata is often sparse and, at times, erroneous. Additionally, it is prohibitively expensive to address these limitations through traditional, manual means. This paper reports on research that applies machine-driven approaches to analyzing digitized fish images and extracting various important features from them. The digitized fish specimens are being analyzed as part of the Biology Guided Neural Networks (BGNN) initiative, which is developing a novel class of artificial neural networks using phylogenies and anatomy ontologies. Automatically generated metadata is crucial for identifying the high-quality images needed for the neural network’s predictive analytics. Methods that combine ML and image informatics techniques allow us to rapidly enrich the existing metadata associated with the 7,244 images from the Illinois Natural History Survey (INHS) used in our study. Results show we can accurately generate many key metadata properties relevant to the BGNN project, as well as general image quality metrics (e.g. brightness and contrast). Results also show that we can accurately generate bounding boxes and segmentation masks for fish, which are needed for subsequent machine learning analyses. The automatic process outperforms humans in terms of time and accuracy, and provides a novel solution for leveraging digitized specimens in ML. This research demonstrates the ability of computational methods to enhance the digital library services associated with the tens of thousands of digitized specimens stored in open-access repositories world-wide.
A high throughput screening assay for inhibitors of SARS-CoV-2 pseudotyped particle entry
Authors: Xu Miao , Pradhan Manisha , Gorshkov Kirill , Petersen Jennifer D. , Shen Min , Guo Hui , Zhu Wei , Klumpp-Thomas Carleen , Michael Sam , Itkin Misha , Itkin Zina , Straus Marco R. , Zimmerberg Joshua , Zheng Wei , Whittaker Gary R. , Chen Catherine Z. 
Published: October 2021

AbstractEffective small molecule therapies to combat the SARS-CoV-2 infection are still lacking as the COVID-19 pandemic continues globally. High throughput screening assays are needed for lead discovery and optimization of small molecule SARS-CoV-2 inhibitors. In this work, we have applied viral pseudotyping to establish a cell-based SARS-CoV-2 entry assay. Here, the pseudotyped particles (PP) contain SARS-CoV-2 spike in a membrane enveloping both the murine leukemia virus (MLV) gag-pol polyprotein and luciferase reporter RNA. Upon addition of PP to HEK293-ACE2 cells, the SARS-CoV-2 spike protein binds to the ACE2 receptor on the cell surface, resulting in priming by host proteases to trigger endocytosis of these particles, and membrane fusion between the particle envelope and the cell membrane. The internalized luciferase reporter gene is then expressed in cells, resulting in a luminescent readout as a surrogate for spike-mediated entry into cells. This SARS-CoV-2 PP entry assay can be executed in a biosafety level 2 containment lab for high throughput screening. From a collection of 5,158 approved drugs and drug candidates, our screening efforts identified 7 active compounds that inhibited the SARS-CoV-2-S PP entry. Of these seven, six compounds were active against live replicating SARS-CoV-2 virus in a cytopathic effect assay. Our results demonstrated the utility of this assay in the discovery and development of SARS-CoV-2 entry inhibitors as well as the mechanistic study of anti-SARS-CoV-2 compounds. Additionally, particles pseudotyped with spike proteins from SARS-CoV-2 B.1.1.7 and B.1.351 variants were prepared and used to evaluate the therapeutic effects of viral entry inhibitors.
ORPER: a workflow for constrained SSU rRNA phylogenies
Authors: Cornet Luc , Ahn Anne-Catherine , Wilmotte Annick , Baurain Denis 
Published: October 2021

AbstractThe continuous increase of sequenced genomes in public repositories makes the choice of interesting bacterial strains for future sequencing projects evermore complicated, as it is difficult to estimate the redundancy between these strains and the already available genomes. Therefore, we developed the Nextflow workflow “ORPER” (containerized in Singularity), which allows determining the phylogenetic position of a collection of organisms in the genomic landscape. ORPER constrains the phylogenetic placement of SSU (16S) rRNA sequences in a multilocus reference tree based on ribosomal protein genes extracted from public genomes. We demonstrate the utility of ORPER on the Cyanobacteria phylum, by placing 152 strains of the BCCM/ULC collection.