bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impacts of Morally Distressing Experiences on the Mental Health of Canadian Health Care Workers During the COVID-19 Pandemic
Authors: Plouffe Rachel A. , Nazarov Anthony , Forchuk Callista A. , Gargala Dominic , Deda Erisa , Le Tri , Bourret-Gheysen Jesse , Jackson Brittni , Soares Vanessa , Hosseiny Fardous , Smith Patrick , Roth Maya , MacDougall Arlene G. , Marlborough Michelle , Jetly Rakesh , Heber Alexandra , Albuquerque Joy , Lanius Ruth , Balderson Ken , Dupuis Gabrielle , Mehta Viraj , Richardson J. Don 
Published: April 2021

AbstractObjectiveResearch is urgently needed to understand health care workers’ (HCWs’) experiences of moral-ethical dilemmas encountered throughout the COVID-19 pandemic, and their associations with organizational perceptions and personal well-being. The purpose of this research is to evaluate associations between workplace experiences during COVID-19, moral distress, and the psychological well-being of Canadian HCWs.MethodA total of 1383 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in an online survey. Participants completed measures reflecting moral distress, perceptions of organizational response to the pandemic, burnout, and symptoms of psychological disorders, including depression, anxiety, and posttraumatic stress disorder.ResultsStructural equation modeling showed that when organizational predictors were considered together, resource adequacy, positive work life impact, and ethical work environment negatively predicted severity of moral distress, whereas COVID-19 risk perception positively predicted severity of moral distress. Moral distress also significantly and positively predicted symptoms of depression, anxiety, PTSD, and burnout.ConclusionsOur findings highlight an urgent need for HCW organizations to implement strategies designed to prevent long-term moral and psychological distress within the workplace. Ensuring availability of adequate resources, reducing HCW risk of contracting COVID-19, providing organizational support regarding individual priorities, and upholding ethical considerations are crucial to reducing severity of moral distress in HCWs.
Physiotherapists perceived role in managing anxiety in patients with Relapsing-Remitting Multiple Sclerosis: a mixed-methods study
Authors: Lucas Lauren , Parker Jack 
Published: April 2021

ABSTRACTObjectivesTo explore how physiotherapists manage anxiety in patients with RRMS in community and outpatient settings. To identify further training and research to better develop physiotherapy practice.DesignA mixed-methods design, combining a cross-sectional survey and semi-structured interviews with UK-physiotherapists.ParticipantsSixteen UK-registered physiotherapists: 11 in the survey, 5 in the interviews.MethodsTo inform the qualitative study, a cross-sectional survey collected data from physiotherapists working in neurology to understand the impact and management of anxiety in people with MS (PwMS) during rehabilitation. Analysis used descriptive statistics and the findings formed the interview guide. Semi-structured interviews with specialist physiotherapists explored barriers and facilitators to managing anxiety, physiotherapy training needs and offered suggestions to develop physiotherapy research and practice. Themes were derived inductively.ResultsThe survey suggested how PwMS present with anxiety, its impact during rehabilitation, physiotherapy management practices, and physiotherapist skills and training needs. Five semi-structured interviews with specialist physiotherapists expanded on the survey findings and identified five main themes: Understanding the MS journey, modifying assessment and treatment, anxiety management toolbox, lagging behind Musculoskeletal Physiotherapy, and gaining knowledge and skills.ConclusionPhysiotherapists encounter anxiety in PwMS in community and outpatient rehabilitation and perceive they have a role in managing it as it presents. Facilitators included communication, listening skills and opportunities to develop strong therapeutic relationships. Poor training and support, lack of clinical guidelines and limited research evidence were considered barriers. Clinically relevant learning opportunities, interprofessional working, and greater support through clinical supervision is recommended to better develop physiotherapy practice.Contribution of the paperKey messagesPhysiotherapists perceive they have a role in managing anxiety and psychological wellbeing in PwMS as it presents in community and outpatient neurorehabilitation settings.Opportunities to build strong therapeutic relationships through effective communication and listening skills are considered important in being able to manage patient anxiety effectively.Poor training and support and a lack of clinical guidelines continue to be barriers in this area.New knowledgeOnline CPD facilitated through the CSP website and iCSP learning platform may be beneficial to increase competence in this area.Further research to understand the MS illness experience in relation to rehabilitation is required to better inform physiotherapy practice and identify appropriate psychologically informed physiotherapy interventions.
Exercise and training regulation of autophagy markers in human and rodent skeletal muscle
Authors: Botella Javier , Jamnick Nicholas A. , Granata Cesare , Genders Amanda J. , Perri Enrico , Jabar Tamim , Garnham Andrew , Lazarou Michael , Bishop David J. 
Published: April 2021

AbstractAutophagy is a key intracellular mechanism by which cells degrade old or dysfunctional proteins and organelles. In skeletal muscle, evidence suggests that exercise increases autophagosome content and autophagy flux. However, the exercise-induced response seems to differ between rodents and humans, and little is known about how different exercise prescription parameters may affect these results. The present study utilised skeletal muscle samples obtained from four different experimental studies using rats and humans. Here we show that following exercise, in the soleus muscle of Wistar rats, there is an increase in LC3B-I protein levels (+ 109%) immediately after exercise, and a subsequent increase in LC3B-II protein levels (+ 97%) 3 hours into the recovery. Conversely, in human skeletal muscle, there is an immediate exercise-induced decrease in LC3B-II protein levels (− 24%), independent of whether exercise is performed below or above the maximal lactate steady state, which returns to baseline 3.5 hours following recovery, while no change in LC3B-I protein levels is observed. p62 protein levels did not change in neither rats nor humans following exercise. By employing anex vivoautophagy flux assay previously used in rodents we demonstrate that the exercise-induced decrease in LC3B-II protein levels in humans does not reflect a decreased autophagy flux. Instead, effect size analyses suggest a modest-to-large increase in autophagy flux following exercise that lasts up to 24 hours. Our findings suggest that exercise-induced changes in autophagosome content markers differ between rodents and humans, and that exercise-induced decrease in LC3B-II protein levels do not reflect autophagy flux level.
Can Deep Convolutional Neural Networks Learn Same-Different Relations?
Authors: Puebla Guillermo , Bowers Jeffrey S. 
Published: April 2021

AbstractSame-different visual reasoning is a basic skill central to abstract combinatorial thought. This fact has lead neural networks researchers to test same-different classification on deep convolutional neural networks (DCNNs), which has resulted in a controversy regarding whether this skill is within the capacity of these models. However, most tests of same-different classification rely on testing on images that come from the same pixel-level distribution as the testing images, yielding the results inconclusive. In this study we tested relational same-different reasoning DCNNs. In a series of simulations we show that DCNNs are capable of visual same-different classification, but only when the test images are similar to the training images at the pixel-level. In contrast, even when there are only subtle differences between the testing and training images, the performance of DCNNs could drop to chance levels. This is true even when DCNNs’ training regime included a wide distribution of images or when they were trained in a multi-task setup in which training included an additional relational task with test images from the same pixel-level distribution.
Identification of Structures for Ion Channel Kinetic Models
Authors: Mangold Kathryn E. , Wang Wei , Johnson Eric K. , Bhagavan Druv , Moreno Jonathan D. , Nerbonne Jeanne M. , Silva Jonathan R. 
Published: April 2021

AbstractMarkov models of ion channel dynamics have evolved as experimental advances have improved our understanding of channel function. Past studies have examined various topologies for Markov models of channel dynamics. We present a systematic method for identification of all possible Markov model topologies using experimental data for two types of native voltage-gated ion channel currents: mouse atrial sodium and human left ventricular fast transient outward potassium currents. In addition to optional biophysically inspired restrictions on the number of connections from a state and elimination of long-range connections, this study further suggests successful models have more than minimum number of connections for set number of states. When working with topologies with more than the minimum number of connections, the topologies with three and four connections to the open state tend to serve well as Markov models of ion channel dynamics.Significance StatementHere, we present a computational routine to thoroughly search for Markov model topologies for simulating whole-cell currents given an experimental dataset. We test this method on two distinct types of voltage-gated ion channels that function in the generation of cardiac action potentials. Particularly successful models have more than one connection between an open state and the rest of the model, and large models may benefit from having even more connections between the open state and the rest of the other states.
Activation of the autophagy pathway affects Dengue virus infection inAedes aegypti
Authors: Chen Tse-Yu , Smartt Chelsea T. 
Published: April 2021

AbstractMosquito-borne Dengue virus (DENV) has caused major disease worldwide, impacting 50 to 100 million people every year, and is spread by the major mosquito vectorAedes aegypti. Understanding mosquito physiology and developing new control strategies becomes an important issue to eliminate DENV. We focused on autophagy, a pathway suggested as having a positive influence on virus replication in humans, as a potential anti-viral target in the mosquito. To understand the role played by autophagy inAe. aegypti, we examined the expression of the pathwayin vitro(Aag-2 cell) andin vivo(Ae. aegypti). The results indicated that DENV infection in Aag-2 cells caused the microtubule-associated protein light chain 3-phosphatidylethanolamine conjugate (LC3-II) protein levels to increase which indicated the activation of the autophagy pathway. Rapamycin and 3-Methyladenine were used to activate or suppress the autophagy pathway, respectively. Rapamycin treatment decreased the virus titer in the Aag-2 cells, but the 3-Methyladenine treatment did not affect DENV titer. InAe. aegypti, microinjected rapamycin increased the DENV titer after one-day infection and was significantly different compared to the control group titer. Two ATG genes, ATG4 and ATG12, were expressed differentially under the rapamycin treatments. Although the results differed betweenin vitroandin vivostudies, findings from both support the interaction between autophagy and DENV. Our studies revealed the activation of the autophagy pathway through rapamycin could be related to DENV infection in the mosquito. The possibility of autophagy being associated with different antiviral mechanisms at different extrinsic incubation times and tissues inAe. aegyptiis discussed.Author SummaryDengue virus (DENV) has been a great threat to public health and has not developed an efficient method to stop the transmission. To understand the complex interaction between virus and mosquito, we investigate the autophagy pathway and its role during the infection process. We noticed the induction of autophagy pathways from DENV infection in Aag-2 cells and blood meal fromAe. aegypti. Moreover, activation of the autophagy pathway from rapamycin could alter the DENV titer. Our results indicated the autophagy pathway is associated with DENV and could be crucial during the DENV infection. Furthermore, we proved the practicality of small molecules in altering the autophagy pathway in mosquitoes, and thus the usage of small molecules as possible mosquito pathogen vaccines should be evaluated.
The lysine-rich intracellular loop and cell type-specific co-factors are required for IFITM3 antiviral immunity in hematopoietic stem cells
Authors: Unali G. , Giordano A.M.S , Cuccovillo I. , Alezz M. Abou , Apolonia L. , Merelli I. , Malim M. H. , Petrillo C. , Kajaste-Rudnitski A. 
Published: April 2021

AbstractThe interferon-induced transmembrane protein 3 (IFITM3) inhibits lentiviral gene therapy vector entry into hematopoietic stem cells and can be overcome by Cyclosporine H (CsH), but underlying mechanisms remain unclear. Here, we show that mutating the evolutionarily conserved lysines of the IFITM3 intracellular loop abolishes its antiviral activity without affecting either its localization or its degradation by CsH through non-canonical lysosomal pathways. When confined to the plasma membrane, the lysine-competent IFITM3 lost restriction against VSV-G pseudotyped viral vectors but gained antiviral activity against vectors that fuse directly at the plasma membrane. Interestingly, altering the lysines did not alter IFITM3 homodimerization but impacted higher-order protein complex formation, suggesting loss of interaction with cellular co-factors. In agreement, IFITM3 expression was not sufficient to restrict viral vectors in myeloid K562 cells as opposed to promonocytic THP1 or primary HSC. We exclude the involvement of previously identified factors affecting IFITM3 biology and propose a novel model for IFITM3 restriction that depends on the presence of cellular co-factor(s) that may interact with IFITM3 through the intracellular loop lysine residues. Overall, our work provides significant insight into the mechanisms of action of IFITM3 and CsH that can be exploited for improved gene therapies and broadly acting antiviral strategies.
Integrative structural modelling of macromolecular complexes using Assembline
Authors: Rantos Vasileios , Karius Kai , Kosinski Jan 
Published: April 2021

AbstractIntegrative modelling enables structure determination of macromolecular complexes by combining data from multiple experimental sources such as X-ray crystallography, electron microscopy (EM), or crosslinking mass spectrometry (XL-MS). It is particularly useful for complexes not amenable to high-resolution EM—complexes that are flexible, heterogenous, or imaged in cells with cryo-electron tomography. We have recently developed an integrative modelling protocol that allowed us to model multi-megadalton complexes as large as the nuclear pore complex. Here, we describe the Assembline software package, which combines multiple programs and libraries with our own algorithms in a streamlined modelling pipeline. Assembline builds ensembles of models satisfying data from atomic structures or homology models, EM maps and other experimental data, and provides tools for their analysis. Comparing to other methods, Assembline enables efficient sampling of conformational space through a multi-step procedure, provides new modeling restraints, and includes a unique configuration system for setting up the modelling project. Our protocol achieves exhaustive sampling in less than 100 – 1,000 CPU-hours even for complexes in the megadalton range. For larger complexes, resources available in institutional or public computer clusters are needed and sufficient to run the protocol. We also provide step-by-step instructions for preparing the input, running the core modelling steps, and assessing modelling performance at any stage.
Plasma microbiome in COVID-19 subjects: an indicator of gut barrier defects and dysbiosis
Authors: Prasad Ram , Patton Michael John , Floyd Jason L , Vieira Cristiano Pedrozo , Fortmann Seth , DuPont Mariana , Harbour Angie , Jeremy Chen See , Wright Justin , Lamendella Regina , Stevens Bruce R. , Grant Maria B. 
Published: April 2021

AbstractThe gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) symptoms. We asked whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n=30) and healthy control (n=16) were collected during hospitalization. Plasma microbiome was analyzed using 16S rRNA sequencing, metatranscriptomic analysis, and gut permeability markers including FABP-2, PGN and LPS in both patient cohorts. Almost 65% (9 out 14) COVID-19 patients showed abnormal presence of gut microbes in their bloodstream. Plasma samples contained predominatelyProteobacteria, Firmicutes,andActinobacteria. The abundance of gram-negative bacteria (Acinetobacter, Nitrospirillum, Cupriavidus, Pseudomonas, Aquabacterium, Burkholderia, Caballeronia, Parabhurkholderia, Bravibacterium,andSphingomonas) was higher than the gram-positive bacteria (StaphylococcusandLactobacillus) in COVID-19 subjects. The levels of plasma gut permeability markers FABP2 (1282±199.6vs838.1±91.33; p=0.0757), PGN (34.64±3.178vs17.53±2.12; p<0.0001), and LPS (405.5±48.37vs249.6±17.06; p=0.0049) were higher in COVID-19 patients compared to healthy subjects. These findings support that the intestine may represent a source for bacteremia and may contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.
The Mechanism of Activation of Monomeric B-Raf V600E
Authors: Maloney Ryan C. , Zhang Mingzhen , Jang Hyunbum , Nussinov Ruth 
Published: April 2021

AbstractOncogenic mutations in the serine/threonine kinase B-Raf, particularly the V600E mutation, are frequent in cancer, making it a major drug target. Although much is known about B-Raf’s active and inactive states, questions remain about the mechanism by which the protein changes between these two states. Here, we utilize molecular dynamics to investigate both wild-type and V600E B-Raf to gain mechanistic insights into the impact of the Val to Glu mutation. The results show that the wild-type and mutant follow similar activation pathways involving an extension of the activation loop and an inward motion of the αC-helix. The V600E mutation, however, destabilizes the inactive state by disrupting hydrophobic interactions present in the wild-type structure while the active state is stabilized through the formation of a salt bridge between Glu600 and Lys507. Additionally, when the activation loop is extended, the αC-helix is able to move between an inward and outward orientation as long as the DFG motif adopts a specific orientation. In that orientation Phe595 rotates away from the αC-helix, allowing the formation of a salt bridge between Lys483 and Glu501. These mechanistic insights have implications for the development of new Raf inhibitors.
Captive-breeding and catch-and-release’s effects on the reproductive success of Atlantic salmon (Salmo salarL.)
Authors: Bouchard R. , Wellband K. , Lecomte L. , Bernatchez L. , April J. 
Published: April 2021

AbstractCaptive-breeding programs as well as and catch-and-release are among the most commonly adopted conservation practices in recreational fisheries. However, risks and benefits associated with their implementation are rarely evaluated. In the case of Atlantic Salmon, while previous studies revealed that captive-bred fish show reduced fitness compared to their wild counterparts in nature. Yet, few examined the extent and causes of their reduced reproductive success or directly compared their contribution to enhance genetic diversity to that of wild fish, including mature male parr. Furthermore, only one study specifically measured the reproductive success of caught and released Atlantic salmon in natural settings, and no study to date evaluated if released salmon are able to reproduce when released at temperature above 20°C which is known to increase post-release mortality. Here, we use high-throughput microsatellite sequencing of 38 loci to accurately assign 2500 offspring to a comprehensive set of possible parents from a supplemented Atlantic salmon population in Québec, Canada. The resolved molecular pedigree provided informative insight on the reproductive pattern of both captive-bred salmon and caught-and-released salmon. Captive-bred salmon had fewer partners than their wild conspecifics which lead to a significant reduction of reproductive success relative to that of their wild counterparts. Supplementation of captive-bred salmon significantly contributed to increase genetic diversity but mature male parr did so to an even greater extent and significantly inflated the number of alleles found among offspring. Moreover, our results showed that that at least 83% of caught-and-released salmon did successfully reproduced although caught-and-released female salmon have a significantly reduced reproductive success, averaging 73% of the reproductive output of non-caught salmon. Reproductive success of released salmon was not influenced by water temperature over 20°C which suggests either that the studied population is locally adapted to warm waters or that they behaviorally regulated body temperature by accessing nearby thermal refugia. Our results should help refining managers’ ability to analyze the risks and benefits associated with captive-breeding and catch-and-release, and thus, optimize conservation practices used for the preservation of Atlantic salmon populations.
Heritable variation in locomotion, reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel
Authors: Bailey Lauren S. , Bagley Jared R. , Dodd Rainy , Olson Ashley , Bolduc Mikayla , Philip Vivek M. , Reinholdt Laura G. , Sukoff Rizzo Stacey J. , Gagnon Leona , Chesler Elissa J. , Jentsch J. David 
Published: April 2021

AbstractDrugs of abuse, including alcohol and stimulants like cocaine, produce effects that are subject to individual variability, and genetic variation accounts for at least a portion of those differences. Notably, research in both animal models and human subjects point towards reward sensitivity and impulsivity as being trait characteristics that predict relatively greater positive subjective responses to stimulant drugs. Here we describe use of the eight Collaborative Cross (CC) founder strains and multiple CC strains to examine the heritability of reward sensitivity and impulsivity traits, as well as genetic correlations between these measures and existing addiction-related phenotypes.Methods. Strains were all tested for activity in an open field and reward sensitivity (intake of chocolate BOOST®). Mice were then divided into two counterbalanced groups and underwent reversal learning (impulsive action and waiting impulsivity) or delay discounting (impulsive choice).Results. CC and founder mice demonstrate significant heritability for impulsive action, impulsive choice, waiting impulsivity, locomotor activity, and reward sensitivity, with each impulsive phenotype determined to be non-correlating, independent traits. This research was conducted within the broader, inter-laboratory effort of the Center for Systems Neurogenetics of Addiction (CSNA) to characterize CC and DO mice for multiple, cocaine abuse related traits. These data will facilitate the discovery of genetic correlations between predictive traits, which will then guide discovery of genes and genetic variants that contribute to addictive behaviors.