bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease correlates of quantitative susceptibility mapping rim lesions in multiple sclerosis
Authors: Marcille Melanie , Rúa Sandra Hurtado , Tyshkov Charles , Jaywant Abhishek , Comunale Joseph , Kaunzner Ulrike W. , Nealon Nancy , Perumal Jai S. , Zexter Lily , Zinger Nicole , Bruvik Olivia , Wang Yi , Sweeney Elizabeth , Kuceyeski Amy , Nguyen Thanh D. , Gauthier Susan A. 
Published: June 2021

AbstractObjectiveThis study aimed to explore the association between chronic active rim+ lesions, identified as having a hyperintense rim on quantitative susceptibility mapping (QSM), on both clinical disability and imaging measures of neurodegeneration in patients with multiple sclerosis.MethodsThe patient cohort was composed of 159 relapsing remitting multiple sclerosis patients aged 42.17 ± 10.25 years and disease duration of 10.74 ± 7.51 years. The Brief International Cognitive Assessment for Multiple Sclerosis and Expanded Disability Status Scale (EDSS) were used to assess clinical disability. Cortical thickness and thalamic volume were evaluated as imaging measures of neurodegeneration.ResultsA total of 4,469 multiple sclerosis lesions were identified, of which 171 QSM rim+ (3.8%) lesions were identified among 57 patients (35.9%). In a multivariate regression model, as the overall total lesion burden increased, patients with at least one rim+ lesion on QSM performed worse on both physical disability and cognitive assessments, specifically the Symbol Digit Modalities Test (p=0.010), California Verbal Learning Test-II (p=0.030), and EDSS (p=0.001). In a separate univariate regression model, controlling for age (p<0.001), having at least one rim+ lesion was related to more cortical thinning (p= 0.03) in younger patients (< 45 years). Lower thalamic volume was associated with older patients (p=0.038) and larger total lesion burden (p<0.001) however, the association did not remain significant with rim+ lesions (p=0.10).InterpretationOur findings demonstrate the significant impact of chronic active lesions, as identified on QSM, on both clinical disability and imaging measures of neurodegeneration in patients with multiple sclerosis.
The Digital Analytic Patient Reviewer (DAPR) for COVID-19 Data Mart Validation
Authors: Park Heekyong , Wang Taowei David , Wattanasin Nich , Castro Victor M. , Gainer Vivian , Goryachev Sergey , Murphy Shawn 
Published: June 2021

AbstractObjectiveTo provide high-quality data for COVID-19 research, we validated COVID-19 clinical indicators and 22 associated computed phenotypes, which were derived by machine learning algorithms, in the Mass General Brigham (MGB) COVID-19 Data Mart.Materials and MethodsFifteen reviewers performed a manual chart review for 150 COVID-19 positive patients in the data mart. To support rapid chart review for a wide range of target data, we offered the Digital Analytic Patient Reviewer (DAPR). DAPR is a web-based chart review tool that integrates patient notes and provides note search functionalities and a patient-specific summary view linked with relevant notes. Within DAPR, we developed a COVID-19 validation task-oriented view and information extraction logic, enabled fast access to data, and considered privacy and security issues.ResultsThe concepts for COVID-19 positive cohort, COVID-19 index date, COVID-19 related admission, and the admission date were shown to have high values in all evaluation metrics. For phenotypes, the overall specificities, PPVs, and NPVs were high. However, sensitivities were relatively low. Based on these results, we removed 3 phenotypes from our data mart. In the survey about using the tool, participants expressed positive attitudes towards using DAPR for chart review. They assessed the validation was easy and DAPR helped find relevant information. Some validation difficulties were also discussed.Discussion and ConclusionDAPR’s patient summary view accelerated the validation process. We are in the process of automating the workflow to use DAPR for chart reviews. Moreover, we will extend its use case to other domains.
Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity
Authors: Groß Rüdiger , Zanoni Michelle , Seidel Alina , Conzelmann Carina , Gilg Andrea , Krnavek Daniela , Erdemci-Evin Sümeyye , Mayer Benjamin , Hoffmann Markus , Pöhlmann Stefan , Beil Alexandra , Kroschel Joris , Jahrsdörfer Bernd , Schrezenmeier Hubert , Kirchhoff Frank , Münch Jan , Müller Janis A. 
Published: June 2021

AbstractHeterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. We aimed to evaluate the reactogenicity, humoral and cellular immune responses towards different SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination and analyzed a cohort of 26 individuals aged 25-46 (median 30.5) years that received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8- week interval. Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and less severe after the BNT162b2 boost. Antibody titers increased significantly over time resulting in strong neutralization titers two weeks after the BNT162b2 boost. Neutralizing activity against the prevalent strain B.1.1.7 (Alpha) and immune-evading VOC B.1.351 (Beta) was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was seen in neutralization of VOI B.1.617 (Kappa). In addition, the heterologous vaccination induced CD4+ and CD8+ T cells reactive to SARS-CoV-2 spike peptides of all analyzed variants; Wuhan-Hu-1, B.1.1.7, B.1.351, and P.1 (Gamma). In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination regimen is not associated with serious adverse events and results in a potent humoral immune response and elicits T cell reactivity. Variants B.1.1.7, B.1.351 and B.1.617.1 are potently neutralized by sera of all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations.
U-RISC: an ultra-high-resolution electron microscopy dataset challenging existing deep learning algorithms
Authors: Shi Ruohua , Wang Wenyao , Li Zhixuan , He Liuyuan , Sheng Kaiwen , Ma Lei , Du Kai , Jiang Tingting , Huang Tiejun 
Published: June 2021

AbstractConnectomics is a developing field aiming at reconstructing the connection of the neural system at nanometer scale. Computer vision technology, especially deep learning methods used in image processing, has promoted connectomic data analysis to a new era. However, the performance of the state-of-the-art methods still falls behind the demand of scientific research. Inspired by the success of ImageNet, we present the U-RISC, an annotated Ultra-high Resolution Image Segmentation dataset for Cell membrane, which is the largest cell membrane annotated Electron Microscopy (EM) dataset with a resolution of 2.18nm/pixel. Multiple iterative annotations ensured the quality of the dataset. Through an open competition, we reveal that the performance of current deep learning methods still has a considerable gap with human-level, different from ISBI 2012, on which the performance of deep learning is close to human. To explore the causes of this discrepancy, we analyze the neural networks with a visualization method, attribution analysis. We find that in U-RISC, it requires a larger area around a pixel to predict whether the pixel belongs to the cell membrane or not. Finally, we integrate currently available methods to provide a new benchmark (0.67, 10% higher than the leader of competition, 0.61) for cell membrane segmentation on U-RISC and propose some suggestions in developing deep learning algorithms. The U-RISC dataset and the deep learning codes used in this paper will be publicly available.
Quality of Cervical Cancer Screening at a Family Health Unit in Salvador-BA
Authors: Freitas Coelho Julita Maria , Da Silva Jamilly Souza , Fonsêca Santos Letícia , França Lyvia Mirelle Carneiro , Ponte Gláucia Alencar , De Assis Sampaio Lorena Moura , Galvão Caroline Ramalho , Galvão Lorena Ramalho , Santos Dantas Bruna Matos , Santos Conceição Sarah Dos , Dias Gomes Érica Velasco , Cirqueira Silva Maria Emília , Oliveira Ana Clara Silva , Silva Caroline Santos 
Published: June 2021

ABSTRACTIntroductionCytopathological examination is the main method for the screening of cervical cancer, its occurrence can be prevented or minimized through screening, with good coverage, quality of collection and analysis and women’s adherence to the examination.ObjectiveTo describe the quality of cytopathological exams performed at a family health unit in Salvador - Bahia during the years 2015 and 2016.MethodA cross-sectional study, of an exploratory descriptive character, was conducted, using a database from a previous study carried out in a health unit in Salvador / BA and approved by the Ethical Committee from State University of Feira de Santana.ResultsPreventive gynecological exams of 1,350 women were analyzed, but 330 (24.4%) of them could not be evaluated due to the absence of the report in the health unit and the presence of acellular or hypocellular material that prevented the analysis. From 1020 exams, 45 (3.3%) presented an unsatisfactory sample, without conditions for analysis, while 589 (43.19%) showed only squamous cells. From 392 (29.0%) reports with an adequate study sample, 150 (%) were women with a mean age of 38.49 years. These were located and composed the final sample of the present investigation.Final ConsiderationsWe suggest the need for investments in continuing education for professionals involved in performing cytopathological exams, in order to ensure the right of women to comprehensive and quality health care.
High Speed Photographic Detection of Particle Distribution During Aerosol and Smoke Generating Surgical Procedures: Effects of Surgical Site Evacuation
Authors: Bolk Kody G. , Dunham Michael E. , Hoffseth Kevin F. , Jung Jangwook P , Garcia Beatriz M. , Walvekar Rohan R. 
Published: June 2021

AbstractObjectiveDetermine the effectiveness of evacuation systems designed to clear bioaerosols and smoke from the surgical field.Study designHigh-speed photographic evaluation of aerosol and smoke generated in simulated surgical fields.Materials and methodsSurgical site aerosol clearance was evaluated using a model of the anterior neck and prototypes for surgical site evacuator ports created using 3D printing. A commercially available electrocautery handpiece fitted with an evacuator was tested on animal tissue for smoke clearance. Both systems were connected to a commercial vacuum powered evacuation system. High speed photography was used to record videos of the aerosols and plumes. Fields were recorded with and without evacuation.ResultsEfficient aerosol clearance from an open surgical field using an evacuator port is dependent upon the port design, airflow velocity, and placement relative to the aerosol generating site. The size and surface geometry of the surgical field are also important.Surgical smoke generated with electrocautery is cleared from the field by the evacuation enclosure around the handpiece, even at high electrocautery power settings. Except for device noise, there appears to be no reason for using evacuator flow rates below the maximum setting.ConclusionsBioaerosol and smoke generated during surgery are potential sources of respiratory pathogens and pose a threat to operating room personnel. Surgical site evacuation can significantly reduce the volume of airborne particles in the field but requires careful design and deployment considerations.x
A molecular toolbox for ADP-ribosyl binding proteins
Authors: Sowa Sven T. , Galera-Prat Albert , Wazir Sarah , Alanen Heli I. , Maksimainen Mirko M. , Lehtiö Lari 
Published: June 2021

AbstractProteins interacting with ADP-ribosyl groups are often involved in disease-related pathways or in viral infections, which makes them attractive targets for the development of inhibitors. Our goal was to develop a robust and accessible assay technology that is suitable for high-throughput screening and applicable to a wide range of proteins acting as either hydrolysing or non-hydrolysing binders of mono- and poly-ADP-ribosyl groups. As a foundation of our work, we developed a C-terminal protein fusion tag based on a Gi protein alpha subunit peptide (GAP), which allows for site-specific introduction of cysteine-linked mono- and poly-ADP-ribosyl groups as well as chemical ADP-ribosyl analogs. By fusion of the GAP-tag and ADP-ribosyl binders to fluorescent proteins, we were able to generate robust FRET signals and the interaction with 22 previously described ADP-ribosyl-binders was confirmed. To demonstrate the applicability of this binding assay for high-throughput screening, we utilized it to screen for inhibitors of the SARS-CoV-2 nsp3 macrodomain and identified the drug suramin as a moderate yet unspecific inhibitor of this protein. To complement the binding technology, we prepared high-affinity ADP-ribosyl binders fused to a nanoluciferase, which enabled simple blot-based detection of mono- and poly-ADP-ribosylated proteins. These tools can be expressed recombinantly inE. coliusing commonly available agents and will help to investigate ADP-ribosylation systems and aid in drug discovery.
Species-specific molecular barriers to SARS-CoV-2 replication in bat cells
Authors: Aicher Sophie-Marie , Streicher Felix , Chazal Maxime , Planas Delphine , Luo Dongsheng , Buchrieser Julian , Nemcova Monika , Seidlova Veronika , Zukal Jan , Serra-Cobo Jordi , Pontier Dominique , Schwartz Olivier , Pikula Jiri , Dacheux Laurent , Jouvenet Nolwenn 
Published: June 2021

AbstractBats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the susceptibility of primary cells from Rhinolophus ferrumequinum and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis and Nyctalus noctula, to SARS-CoV-2 infection. None of these cells were sensitive to infection, not even the ones expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), which serves as the viral receptor in many mammalian species. The resistance to infection was overcome by expression of human ACE2 (hACE2) in three cell lines, suggesting that restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or absence of bACE2 binding in these cells. Infectious virions were produced but not released from hACE2-transduced M. myotis brain cells. E. serotinus brain cells and M. myotis nasal epithelial cells expressing hACE2 efficiently controlled viral replication. This ability to control viral replication correlated with a potent interferon response. Our data highlight the existence of species-specific molecular barriers to viral replication in bat cells. These novel chiropteran cellular models are valuable tools to investigate the evolutionary relationships between bats and coronaviruses.Author summaryBats host ancestors of several viruses that cause serious disease in humans, as illustrated by the on-going SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions have been hampered by a limited number of bat cell lines. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The varying susceptibilities of the cells to SARS-CoV-2 infection offered the opportunity to uncover some species-specific molecular restrictions to viral replication. All bat cells exhibited a potent entry-dependent restriction. Once this block was overcome by over-expression of human ACE2, which serves at the viral receptor, two bat cell lines controlled well viral replication, which correlated with the inability of the virus to counteract antiviral responses. Other cells potently inhibited viral release. Our novel bat cellular models contribute to a better understanding of the molecular interplays between bats and viruses.
GFI1 tethers the NuRD complex to open and transcriptionally active chromatin in myeloid progenitors
Authors: Helness Anne , Fraszczak Jennifer , Joly-Beauparlant Charles , Bagci Halil , Trahan Christian , Arman Kaifee , Shooshtarizadeh Peiman , Chen Riyan , Ayoub Marina , Côté Jean-François , Oeffinger Marlene , Droit Arnaud , Möröy Tarik 
Published: June 2021

ABSTRACTGFI1 is a SNAG-domain, DNA binding transcriptional repressor which controls myeloid differentiation, in particular the formation of neutrophils. Here we show that GFI1 interacts with the chromodomain helicase CHD4 and other components of the “Nucleosome remodeling and deacetylase” (NuRD) complex. In granulo-monocytic precursors, GFI1, CHD4 or GFI1/CHD4 complexes occupy sites of open chromatin enriched for histone marks associated with active transcription suggesting that GFI1 recruits the NuRD complex to target genes that are regulated by active or bivalent promoters and active enhancers. Our data also show that GFI1 and GFI1/CHD4 complexes occupy promoters of different sets of genes that are either enriched for IRF1 or SPI-1 consensus sites, respectively. During neutrophil differentiation, overall chromatin closure and depletion of H3K4me2 occurs at different degrees depending on whether GFI1, CHD4 or both are present, indicating that GFI1 affects the chromatin remodeling activity of the NuRD complex. Moreover, GFI1/CHD4 complexes regulate chromatin openness and histone modifications differentially to enable regulation of target genes affecting the signaling pathways of the immune response or nucleosome organization or cellular metabolic processes.
Spatial regulation of coordinated excitatory and inhibitory synaptic plasticity at dendritic synapses
Authors: Ravasenga Tiziana , Ruben Massimo , Polenghi Alice , Petrini Enrica Maria , Barberis Andrea 
Published: June 2021

SummaryThe induction of synaptic plasticity at an individual dendritic glutamatergic spine can affect neighboring spines. This local modulation generates dendritic plasticity microdomains believed to expand the neuronal computational capacity. Here, we investigate whether local modulation of plasticity can also occur between glutamatergic synapses and adjacent GABAergic synapses. Using MNI-glutamate and DPNI-GABA double uncaging combined with electrophysiology, live-cell imaging and single-particle tracking, we find that the induction of LTP at an individual glutamatergic spine causes the depression of nearby GABAergic inhibitory synapses (within 3 microns), whereas more distant ones are potentiated. Notably, L-type calcium channels and calpain are required for this plasticity spreading. Overall, our data support a model whereby input-specific glutamatergic postsynaptic potentiation induces a spatially-regulated rearrangement of inhibitory synaptic strength in the surrounding area through short-range heterosynaptic interactions. Such local coordination of excitatory and inhibitory synaptic plasticity is expected to profoundly influence dendritic information processing and integration.
Drosophilaarchitectural protein CTCF is not essential for fly survival and is able to function independently of CP190
Authors: Kyrchanova Olga , Klimenko Natalia , Postika Nikolay , Bonchuk Artem , Zolotarev Nicolay , Maksimenko Oksana , Georgiev Pavel 
Published: June 2021

AbstractCTCF is the most likely ancestor of proteins that contain large clusters of C2H2 zinc finger domains (C2H2) and is conserved among most bilateral organisms. In mammals, CTCF functions as the main architectural protein involved in the organization of topology-associated domains (TADs). In vertebrates andDrosophila, CTCF is involved in the regulation of homeotic genes. Previously, null mutations in thedCTCFgene were found to result in death during the stage of pharate adults, which failed to eclose from their pupal case. Here, we obtained several new nulldCTCFmutations and found that the complete inactivation of dCTCF appears to be limited to phenotypic manifestations of theAbd-Bgene and fertility of adult flies. Many modifiers that are not associated with an independent phenotypic manifestation can significantly enhance the expressivity of the nulldCTCFmutations, indicating that other architectural proteins are able to functionally compensate for dCTCF inactivation inDrosophila. We also mapped the 715–735 aa region of dCTCF as being essential for the interaction with the BTB (Broad-Complex, Tramtrack, and Bric a brac) and microtubule-targeting (M) domains of the CP190 protein, which binds to many architectural proteins. However, the mutational analysis showed that the interaction with CP190 was not essential for the functional activity of dCTCFin vivo.HighlightsThe dCTCF 715–735 aa region interacts with the BTB and M domains of CP190Interaction with CP190 is not essential for dCTCF functionin vivoNulldCTCFmutants are viable but show severely reduced fertility
Loss of Stk11 in basolateral amygdalar projection neurons impairs taste aversion learning by altering the temporal pattern of taste response plasticity in gustatory cortex
Authors: Nanu Roshan D. , Murdy Thomas J. , Levitan David , Scott Seneca , Nelson Sacha B. , Katz Donald B. 
Published: June 2021

AbstractGustatory cortex (GC) responds to tastes on the tongue with dynamic ensemble activity that represents first the presence, then the identity, and finally the hedonic value (palatability) of tastes. This final state of the taste response is uniquely altered by conditioned taste aversion (CTA) – a powerful one-trial learning paradigm in which a taste becomes aversive after association with gastric malaise – a process requiring coordination between GC and basolateral amygdala (BLA). Previously, we found that one key requirement for learning in this circuit is expression of the serine/threonine kinase 11 (Stk11) gene (a tumor suppression gene which has only recently been associated with learning; Levitan et al., 2020). When Stk11 is knocked out in BLA projection neurons (BLApn), CTA learning fails to occur. Here we have examined how learning-related response plasticity in GC taste responses is impacted by the knockout of Stk11 in BLApn. Contrary to the commonly held assumption that a lack of learning means a lack of such plasticity, but consistent with the fact that Stk11KO has been shown to increase the excitability of BLApn, our data reveal that the knockout of Stk11 in BLApn does not eliminate plasticity; rather, it shifts the impact of CTA training on GC taste responses to an earlier, learning-inappropriate epoch. Even naïve taste representations are altered—specifically, the pattern of similarities and differences among the different taste responses are rendered abnormal by Stk11 KO, and these relationships fail to change with training. Finally, the latency of behavior-related dynamic ensemble features of the GC taste response, which is also abnormal in naïve KO mice, is rendered disorganized by CTA. Together, these results suggest that Stk11 plays a role in governing the coordination of GC activity by BLA, and demonstrate that alterations in the function of BLApn caused by Stk11KO inhibit learning not by inhibiting plasticity but by changing its temporal properties.