bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotion Down- and Up-Regulation Act on Spatially Distinct Brain Areas: Interoceptive Regions to Calm Down and Other Affective Regions to Amp Up
Authors: Min Jungwon , Nashiro Kaoru , Yoo Hyun Joo , Cho Christine , Nasseri Padideh , Bachman Shelby L. , Porat Shai , Thayer Julian F. , Chang Catie , Lee Tae-ho , Mather Mara 
Published: September 2021

AbstractPrior studies on emotion regulation identified a set of brain regions specialized for generating and controlling affect. Researchers generally agree that when up- and down-regulating emotion, control regions in the prefrontal cortex turn up or down activity in affect-generating areas. However, the assumption that turning up and down emotions produces opposite effects in the same affect-generating regions is untested. We call this assumption the ‘affective dial hypothesis.’ Our study tested this hypothesis by examining the overlap between the sets of regions activated during up-regulation and those deactivated during down-regulation in a large number of participants (N=105). We found that up- and down-regulation both recruit regulatory regions such as the inferior frontal gyrus and dorsal anterior cingulate gyrus but act on distinct affect-generating regions. While up-regulation increases BOLD signal in regions associated with emotion such as the amygdala, anterior insula, striatum and anterior cingulate gyrus as well as in regions associated with sympathetic vascular activity such as periventricular white matter, down-regulation decreases signal in regions receiving interoceptive input such as the posterior insula and postcentral gyrus. These findings indicate that up- and down-regulation do not generally exert opposing effects on the same affect-generating regions. Instead, they target different brain circuits.Significance StatementMany contexts require modulating one’s own emotions. Identifying the brain areas implementing these regulatory processes should advance understanding emotional disorders and designing potential interventions. The emotion regulation field has an implicit assumption we call the affective dial hypothesis: that both emotion up- and down-regulation modulate the same emotion-generating brain areas. Countering the hypothesis, our findings indicate that up- and down-modulating emotions target different brain areas. Thus, the mechanisms underlying emotion regulation differ more than previously appreciated for up- versus down-regulation. In addition to their theoretical importance, these findings are critical for researchers attempting to target activity in particular brain regions during an emotion regulation intervention.
Functional and Structural Characterization of OXA-935, a Novel OXA-10-family β-lactamase from Pseudomonas aeruginosa
Authors: Pincus Nathan , Rosas-Lemus Monica , Gatesy Samuel , Shuvalova Ludmilla , Brunzelle Joseph , Minasov George , Satchell Karla , Lebrun-Corbin Marine , Ozer Egon , Hauser Alan , Bachta Kelly 
Published: September 2021

ABSTRACTResistance to antipseudomonal penicillins and cephalosporins is often driven by the overproduction of the intrinsic β-lactamase AmpC. However, OXA-10-family β-lactamases are a rich source of resistance in Pseudomonas aeruginosa. OXA β-lactamases have a propensity for mutation leading to extended spectrum cephalosporinase and carbapenemase activity. In this study, we identified isolates from a subclade of the multidrug-resistant (MDR) high risk clonal complex CC446 with resistance to ceftazidime. Genomic analysis revealed that these isolates harbored a plasmid containing a novel allele of blaOXA-10, named blaOXA-935, which was predicted to produce an OXA-10 variant with two amino acid substitutions: an aspartic acid instead of glycine at position 157 and a serine instead of phenylalanine at position 153. The G157D mutation, present in OXA-14, is associated with resistance to ceftazidime. Deletion of blaOXA-935 restored sensitivity to ceftazidime and susceptibility profiling of P. aeruginosa laboratory strains expressing blaOXA-935 revealed that OXA-935 conferred ceftazidime resistance. To better understand the impact of the variant amino acids, we determined the crystal structures of OXA-14 and OXA-935. In OXA-14, one of two monomers contained the canonical carbamylated lysine-70 (K70). In contrast, both monomers of OXA-935 were decarbamylated at K70, and the F153S mutation conferred increased flexibility to the omega (Ω) loop. Compared to OXA-14, the catalytic efficiency of OXA-935 for nitrocefin was significantly reduced. Amino acid changes that confer extended spectrum cephalosporinase activity to OXA-10-family β-lactamases are concerning given rising reliance on novel β-lactam/β-lactamase inhibitor combinations such as ceftolozane-tazobactam and ceftazidime-avibactam to treat MDR P. aeruginosa infections.
Saliva-based detection of COVID-19 infection in a real-world setting using reagent-free Raman spectroscopy and machine learning
Authors: Ember Katherine , Daoust François , Mahfoud Myriam , Dallaire Frédérick , Zamani Esmat , Tran Trang , Plante Arthur , Diop Mame-Kany , Nguyen Tien , St-Georges-Robillard Amélie , Ksantini Nassim , Lanthier Julie , Filiatrault Antoine , Sheehy Guillaume , Quach Caroline , Trudel Dominique , Leblond Frédéric 
Published: September 2021

SignificanceThe primary method of COVID-19 detection is reverse transcription polymerase chain reaction (RT-PCR) testing. PCR test sensitivity may decrease as more variants of concern arise.AimWe aimed to develop a reagent-free way to detect COVID-19 in a real-world setting with minimal constraints on sample acquisition.ApproachWe present a workflow for collecting, preparing and imaging dried saliva supernatant droplets using a non-invasive, label-free technique – Raman spectroscopy – to detect changes in the molecular profile of saliva associated with COVID-19 infection.ResultsUsing machine learning and droplet segmentation, amongst all confounding factors, we discriminated between COVID-positive and negative individuals yielding receiver operating coefficient (ROC) curves with an area under curve (AUC) of 0.8 in both males (79% sensitivity, 75% specificity) and females (84% sensitivity, 64% specificity). Taking the sex of the saliva donor into account increased the AUC by 5%.ConclusionThese findings may pave the way for new rapid Raman spectroscopic screening tools for COVID-19 and other infectious diseases.
Comparative analysis of human immune responses following SARS-CoV-2 vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S
Authors: Barbeau Dominique J. , Martin Judith M. , Carney Emily , Dougherty Emily , Doyle Joshua D. , Dermody Terence S. , Hoberman Alejandro , Williams John V. , Michaels Marian G. , Alcorn John F. , Duprex W. Paul , McElroy Anita K. 
Published: September 2021

AbstractBackgroundThree SARS-CoV-2 vaccines, two based on mRNA, BNT162b2 and mRNA-1273, and one based on an adenovirus platform, Ad26.COV2.S, received emergency use authorization by the U.S. Food and Drug Administration in 2020/2021. These vaccines displayed clinical efficacy in initial studies against confirmed COVID-19 of 95.0%, 94.1%, and 66.9%, respectively.MethodsIndividuals receiving one of these vaccines were invited to participate in a prospective longitudinal comparative study of immune responses elicited by the three vaccines. In this observational cohort study, humoral responses were evaluated using a SARS-CoV-2 receptor-binding domain (RBD) ELISA and a SARS-CoV-2 virus neutralization assay at mean of 21-31 days and 45-63 days following each initial vaccination. IFN-γ ELISPOT assays were conducted with peripheral blood mononuclear cells obtained at a median of 45-63 days after each initial vaccination.ResultsThe two mRNA-based platforms elicited similar RBD ELISA responses and neutralizing antibody responses. The adenovirus-based vaccine elicited significantly lower RBD ELISA and SARS-CoV-2 virus neutralization activity. The mRNA-1273 vaccine elicited significantly higher spike glycoprotein-specific T cell responses than either the BNT162b2 or the Ad26.COV2.S vaccines.ConclusionsBoth mRNA based vaccines elicited higher magnitude humoral responses than Ad26.COV2.S and mRNA1273 elicited the highest magnitude of T cell response. Neutralizing antibody titers correlated with reported estimates of vaccine efficacy.Summary of key pointsWe compared antigen specific humoral and T cell responses following vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. Both mRNA based vaccines elicited higher magnitude humoral responses than Ad26.COV2.S and mRNA1273 elicited the highest magnitude of T cell response.
Automated Detection of Candidate Subjects with Cerebral Microbleeds using Machine Learning
Authors: Sundaresan Vaanathi , Arthofer Christoph , Zamboni Giovanna , Dineen Robert A. , Rothwell Peter M. , Sotiropoulos Stamatios N. , Auer Dorothee P. , Tozer Daniel , Markus Hugh S. , Miller Karla L. , Dragonu Iulius , Sprigg Nikola , Alfaro-Almagro Fidel , Jenkinson Mark , Griffanti Ludovica 
Published: September 2021

AbstractCerebral microbleeds (CMBs) appear as small, circular, well defined hypointense lesions of a few mm in size on T2*-weighted gradient recalled echo (T2*-GRE) images and appear enhanced on susceptibility weighted images (SWI). Due to their small size, contrast variations and other mimics (e.g. blood vessels), CMBs are highly challenging to detect automatically. In large datasets (e.g. the UK Biobank dataset), exhaustively labelling CMBs manually is difficult and time consuming. Hence it would be useful to preselect candidate CMB subjects in order to focus on those for manual labelling, which is essential for training and testing automated CMB detection tools on these datasets. In this work, we aim to detect CMB candidate subjects from a larger dataset, UK Biobank, using a machine learning-based, computationally light pipeline. For our evaluation, we used 3 different datasets, with different intensity characteristics, acquired with different scanners. They include the UK Biobank dataset and two clinical datasets with different pathological conditions. We developed and evaluated our pipelines on different types of images, consisting of SWI or GRE images. We also used the UK Biobank dataset to compare our approach with alternative CMB preselection methods using non-imaging factors and/or imaging data. Finally, we evaluated the pipeline’s generalisability across datasets. Our method provided subject-level detection accuracy>80% on all the datasets (withindataset results), and showed good generalisability across datasets, providing a consistent accuracy of over 80%, even when evaluated across different modalities.
Real-world Effectiveness of 2-dose SARS-CoV-2 Vaccination in Kidney Transplant Recipients
Authors: McEvoy Caitríona M. , Lee Anna , Misra Paraish S. , Lebovic Gerald , Wald Ron , Yuen Darren A. 
Published: September 2021

AbstractThe humoral response to two doses of SARS-CoV-2 (Covid-19) vaccine among transplant recipients is inferior to immunocompetent individuals.1 Data on the ‘real-world’ effectiveness of vaccination in kidney transplant recipients [KTRs] are lacking. We performed a cohort study to investigate the impact of vaccination on Covid-19 infection and outcomes in our kidney transplant program.
A new multi-species Protein A-ELISA assay for plague diagnosis in humans and other mammal hosts
Authors: Bezerra Matheus Filgueira , Xavier Camila Cavalcanti , de Almeida Alzira Maria Paiva , de Souza Reis Christian Robson 
Published: September 2021

AbstractBackgroundThe Hemagglutination assay (HA) is widely used in plague diagnosis, however, it has a subjective interpretation and demands high amounts of antigen and other immunobiological supplies. Conventional IgG-ELISA is limited by the need of specific conjugates for multiple plague hosts.MethodsThus, we developed an ELISA Protein A-peroxidase method to detect anti-F1 antibodies across several species, including humans. To determine the cut-off and performance rates, HA results from 288 samples (81 rabbits, 64 humans, 66 rodents and 77 dogs) were used as reference.ResultsOptimal conditions were found with 250ng/well of F1 and 1:500 serum dilution. Protein A-ELISA showed high repeatability and reproducibility. The positive/negative OD ratios were higher in Protein A-ELISA and there was no significant cross-reaction with other pathogenic yersiniae. The overall sensitivity/specificity, area under the curve and Kappa rates for Protein A-ELISA were 93.9/98.9%; 0.993 and 0.938, respectively. Similar results were observed in each species separately. There was a strong agreement between Protein A and IgG assays (kappa=0.973) in independent analysis (n=487).ConclusionsAltogether, the Protein A-ELISA showed high performance when compared both to HA and IgG-ELISA, with a polyvalent single protocol that requires reduced amounts of antigen and can be employed to any plague hosts.
The slower antibody response in myelofibrosis patients after two doses of mRNA SARS-CoV-2 vaccine calls for a third dose
Authors: Fiorino Fabio , Sicuranza Anna , Ciabattini Annalisa , Santoni Adele , Pastore Gabiria , Simoncelli Martina , Polvere Jacopo , Galimberti Sara , Auddino Stefano , Baratè Claudia , Montagnani Francesca , Sammartano Vincenzo , Bocchia Monica , Medaglini Donata 
Published: September 2021

AbstractImmunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile categories with higher risk of mortality after COVID-19 disease compared to healthy people, including patients with myelofibrosis (MF). Available data on the vaccine immune response developed by MF patients, and the impact of the treatment with the inhibitor of JAK-STAT signaling ruxolitimib, are still fragmented to support an informed decision for a third dose for this category of subjects. Here, we show that 76% of MF patients develop spike-specific IgG after the second vaccine dose, but the response has a slower kinetic compared to healthy subjects, suggesting a reduced capability of their immune system to promptly react to vaccination. A reduced ACE2/RBD inhibition binding activity of spike-specific antibodies was also observed, especially in ruxolitimib treated patients. Our results contribute to answer the open question on the induction of the antibody responses in MF patients following vaccination with COVID-19 mRNA vaccines, showing a slow kinetic that support the need for a third dose of SARS-CoV-2 mRNA vaccines.
Immune profile and responses of a novel Dengue DNA vaccine encoding EDIII-NS1 consensus design based on Indo-African sequences
Authors: Sankaradoss Arun , Jagtap Suraj , Nazir Junaid , E-Moula Shefta , Modak Ayan , Fialho Joshuah , Iyer Meenakshi , Shastri Jayanthi S , Dias Mary , Gadepalli Ravisekhar , Aggarwal Alisha , Vedpathak Manoj , Agrawal Sachee , Pandit Awadhesh , Nisheetha Amul , Kumar Anuj , Shafi Mohamed , Balachandra Swathi , Damodar Tina , Masika Moses Muia , Mwaura Patrick , Anzala Omu , Muthumani Kar , Sowdhamini Ramanathan , Medigeshi Guruprasad R. , Roy Rahul , Pattabiraman Chitra , Krishna Sudhir , Sreekumar Easwaran 
Published: September 2021

AbstractFollowing the recent clinical clearance of an Indian DNA COVID-19 vaccine, India and Africa are potential regions where DNA vaccines may become a major delivery system subject to a range of immunological and regulatory scrutiny. The ongoing COVID pandemic highlights the need to tackle viral variants and expand the number of antigens and assess diverse delivery systems. To address some of these key issues, we have created a Dengue DNA vaccine candidate with the EDIII region as the key antigen given the promise of this segment in not causing ADE, a challenge with this disease. In addition, we have added the NS1 region to broaden the immune response. Following a large Dengue viral sequencing exercise in India, complemented with data from east Africa, our approach was to generate a consensus of four serotypes ED3-NS1 vaccine to explore tackling the issue of diversity. OurIn silicostructural analysis of EDIII consensus vaccine sequence revealed that epitopes are structurally conserved and immunogenic across HLA diversity. Vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Furthermore, the DNA vaccination confers protection against DENV challenge in AG129 mice. Finally, assaying of intracellular staining for IFN-γ, immunoglobulin IgG2(a/c) /IgG1 ratios as well as immune gene profiling suggested a strong Th1-dominant immune response. Our Dengue DNA platform with a focus on Indo-African sequences offers an approach for assessing cross reactive immunity in animal models and lays the foundation for human vaccine roll out either as a stand-alone or mix and match strategy.
Metatranscriptomic Signatures of Lung Function in Pediatric Hematopoietic Cell Transplant Candidates
Authors: Zinter Matt S. , Versluys Birgitta A. , Lindemans Caroline A. , Mayday Madeline Y. , Reyes Gustavo , Sunshine Sara , Chan Marilynn , Fiorino Elizabeth , Cancio Maria , Prevaes Sabine , Sirota Marina , Matthay Michael A. , Kharbanda Sandhya , Dvorak Christopher C. , Boelens Jaap J. , DeRisi Joseph L. 
Published: September 2021

ABSTRACTRationaleImpaired baseline lung function is associated with mortality after allogeneic hematopoietic cell transplantation (HCT). Limited knowledge of the molecular pathways that characterize pre-transplant lung function has hindered the development of lung-targeted interventions.ObjectivesTo elucidate the biologic and microbiologic correlates of impaired lung function in pediatric allogeneic HCT candidates.MethodsBetween 2005-2016, 104 patients with malignant and non-malignant disorders ages 4-19 years underwent paired pulmonary function testing (PFT) and bronchoalveolar lavage (BAL) a median of 1-2 weeks prior to allogeneic transplant in Utrecht, the Netherlands. Cryopreserved BAL underwent RNA sequencing followed by alignment to microbial and human reference genomes for microbiome and gene expression analyses.Measurements and Main ResultsAbnormal pulmonary function was recorded in more than half the cohort, consisted most commonly of restriction and impaired diffusion, and was associated with both all-cause and lung-injury related mortality after HCT. BAL microbiome depletion of commensal supraglottic taxa such as Haemophilus and enrichment of nasal and skin taxa such as Staphylococcus were associated with worse measures of lung capacity and gas diffusion. In addition, impaired lung capacity and diffusion were also associated with gene expression signatures of alveolar epithelial proliferation, epithelial-mesenchymal transition, and downregulated immunity, suggesting a post-injury pro-fibrotic response. Detection of microbial depletion and abnormal epithelial gene expression in BAL enhanced the prognostic utility of pre-HCT PFTs for the outcome of post-HCT mortality.ConclusionsThese findings suggest a novel and potentially actionable connection between microbiome depletion, alveolar injury, and pulmonary fibrosis in the pathogenesis of pre-HCT lung dysfunction.
A computational model of CAR T-cell immunotherapy predicts leukemia patient responses at remission, resistance, and relapse
Authors: Liu Lunan , Ma Chao , Zhang Zhuoyu , Chen Weqiang 
Published: September 2021

AbstractAdaptive CD19-targeted CAR (Chimeric Antigen Receptor) T-cell transfer has become a promising treatment for leukemia. Though patient responses vary across different clinical trials, there currently lacks reliable early diagnostic methods to predict patient responses to those novel therapies. Recently, computational models achieve to in silico depict patient responses, with prediction application being limited. We herein established a computational model of CAR T-cell therapy to recapitulate key cellular mechanisms and dynamics during treatment based on a set of clinical data from different CAR T-cell trials, and revealed critical determinants related to patient responses at remission, resistance, and relapse. Furthermore, we performed a clinical trial simulation using virtual patient cohorts generated based on real clinical patient dataset. With input of early-stage CAR T-cell dynamics, our model successfully predicted late responses of various virtual patients compared to clinical observance. In conclusion, our patient-based computational immuno-oncology model may inform clinical treatment and management.
A Comparison of Weighted Stochastic Simulation Methods
Authors: Thomas Payton J , Ahmadi Mohammad , Zheng Hao , Myers Chris J. 
Published: September 2021

1ABSTRACTRare events are of particular interest in biology because rare biochemical events may be catastrophic to a biological system. To estimate the probability of rare events, several weighted stochastic simulation methods have been developed. Unfortunately, the robustness of these methods is questionable. Here, an analysis of weighted stochastic simulation methods is presented. The methods considered here fail to accomplish the task of rare event simulation, in general, suggesting that new methods are necessary to adequately study rare biological events.
The dynamical Matryoshka model: 1. Incoherent neutron scattering functions for lipid dynamics in bilayers
Authors: Bicout Dominique J. , Cisse Aline , Matsuo Tatsuhito , Peters Judith 
Published: September 2021

AbstractFluid lipid bilayers are the building blocks of biological membranes. Although there is a large amount of experimental data using inconsistent quasi-elastic neutron scattering (QENS) techniques to study membranes, very little theoretical works have been developed to study the local dynamics of membranes. The main objective of this work is to build a theoretical framework to study and describe the local dynamics of lipids and derive analytical expressions of inconsistent diffusion functions (ISF) for QENS. As results, we developed the dynamical Matryoshka model which describes the local dynamics of lipid molecules in membrane layers as a nested hierarchical convolution of three motional processes: (i) individual motions described by the vibrational motions of H-atoms; (ii) internal motions including movements of the lipid backbone, head groups and tails, and (iii) molecule movements of the lipid molecule as a whole. The analytical expressions of the ISF associated with these movements are all derived. For use in analyzing the QENS experimental data, we also derived an analytical expression for the aggregate ISF of the Matryoshka model which involves an elastic term plus three inelastic terms of well-separated time scales and whose amplitudes and rates are functions of the lipid motions. And as an illustrative application, we used the aggregated ISF to analyze the experimental QENS data on a lipid sample of multilamellar bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine). It is clear from this analysis that the dynamical Matryoshka model describes very well the experimental data and allow extracting the dynamical parameters of the studied system.