bluuebunny/crossref_metadata_2025_split huggingface dataset:
Information, Involvement, Self-care and Support - The Needs of Caregivers of People with Stroke: A Grounded Theory Approach
Authors: Lobo Elton H. , Frølich Anne , Abdelrazek Mohamed , Rasmussen Lene J. , Grundy John , Livingston Patricia M. , Islam Sheikh Mohammed Shariful , Kensing Finn 
Published: October 2021

AbstractBackgroundGlobally, stroke is a leading cause of death and disability, with most care undertaken by caregivers who are generally family and friends without prior experience of care. The lack of experience or unpreparedness results in feelings of uncertainty, burnout, anxiety, burden, etc. Hence, it is necessary to identify the needs of caregivers to support them in their caregiving journey better and improve the quality of care delivered.MethodsThe study employed a grounded theory methodology that utilizes information gathered from literature reviews and social media to represent the needs and create a storyline visually. The storyline is further refined and evaluated using an online survey of 72 participants recruited through online stroke caregiving communities.ResultsThe study identified four core categories of needs, i.e., information, involvement, self-care and support that need to be delivered at appropriate times to ensure the caregivers feel prepared to assume their role of care and are supported throughout the care trajectory.ConclusionsThere is a need to create a caregiver-centered approach in stroke recovery to ensure limited obstruction to care and reduced uncertainty in recovery. Moreover, through the inclusion of caregivers in the recovery process, it may be possible to reduce the burden of care to the caregiver and ensure the satisfaction of the healthcare system throughout recovery.
Evolution of SARS-CoV-2 immune responses in nursing home residents following full dose of the Comirnaty® COVID-19 vaccine
Authors: Giménez Estela , Alberola Juan , Torres Ignacio , Albert Eliseo , Alcaraz María Jesús , Botija Pilar , Amat Paula , Remigia María José , Beltrán María José , Rodado Celia , Huntley Dixie , Olea Beatriz , Navarro David 
Published: October 2021

ABSTRACTObjectivesThere is scarce information as to the durability of immune responses elicited by the Comirnaty® COVID-19 vaccine in nursing home residents. Here, we assessed SARS-CoV-2-Spike (S)-targeted antibody and functional T cell responses at around 6 months after complete vaccination.MethodsThe sample comprised 46 residents (34 females; age, 60-100 years), of whom 10 had COVID-19 prior to vaccination. Baseline (median of 17.5 days after vaccination) and follow-up (median, 195 days) plasma specimens were available for quantitation of SARS-CoV-2-S antibodies and enumeration of SARS-CoV-2-S-reactive IFN-γ CD4+ and CD8+ T cells by flow cytometry.ResultsIn total, 44/45 participants had detectable SARS-CoV-2-S antibodies at follow-up. Overall, antibody levels were found to decrease (median, 4.8 fold). Antibodies waning was more frequent (P<0.001) in SARS-CoV-2 naïve (29/35) than in recovered (1/10) residents. SARS-CoV-2-S IFN-γ CD8+ T cells were detected in 33/46 and 24/46 at baseline and follow-up, respectively. The figures for CD4+ T cell counterparts were 12/46 and 30/46. Detectable SARS-CoV-2 IFN-γ CD8+ and CD4+ T cell responses at follow-up were more common in recovered (8/10 and 7/10, respectively) than in naïve residents (9/36 and 25/36, respectively). For those with detectable responses at both time points, SARS-CoV-2-S IFN-γ CD8+ T cell frequencies decreased significantly (P=0.001) over time whereas the opposite (P=0.01) was observed in CD4+ T cells.ConclusionAlmost all residents displayed detectable SARS-CoV-2-S-reactive antibodies and T cell responses, respectively, by around 6 months after complete vaccination with Comirnaty® COVID-19 vaccine, albeit generally waning in magnitude over time.
A joint hierarchical model for the number of cases and deaths due to COVID-19 across the boroughs of Montreal
Authors: Michal Victoire , Vanciu Leo , Schmidt Alexandra M. 
Published: October 2021

AbstractMontreal is the epicentre of the COVID-19 pandemic in Canada with highest number of deaths. The cumulative numbers of cases and deaths in the 33 areas of Montreal are modelled through bivariate hierarchical Bayesian models using Poisson distributions. The Poisson means are decomposed in the log scale as the sums of fixed effects and latent effects. The areal median age, the educational level, and the number of beds in long-term care homes are included in the fixed effects. To explore the correlation between cases and deaths inside and across areas, three bivariate models are considered for the latent effects, namely an independent one, a conditional autoregressive model, and one that allows for both spatially structured and unstructured sources of variability. As the inclusion of spatial effects change some of the fixed effects, we extend the Spatial+ approach to a Bayesian areal set up to investigate the presence of spatial confounding.
Impact of Essential Genes on the Success of Genome Editing Experiments Generating 3,313 New Genetically Engineered Mouse Lines
Authors: Elrick Hillary , Peterson Kevin A. , Willis Brandon J. , Lanza Denise G. , Acar Elif F. , Ryder Edward J. , Teboul Lydia , Kasparek Petr , Birling Marie-Christine , Adams David J. , Bradley Allan , Braun Robert E. , Brown Steve D. , Caulder Adam , Codner Gemma F. , DeMayo Francesco J. , Dickinson Mary E. , Doe Brendan , Duddy Graham , Gertsenstein Marina , Goodwin Leslie O. , Hérault Yann , Lintott Lauri G. , Lloyd K. C. Kent , Lorenzo Isabel , Mackenzie Matthew , Mallon Ann-Marie , McKerlie Colin , Parkinson Helen , Ramirez-Solis Ramiro , Seavitt John R. , Sedlacek Radislav , Skarnes William C. , Smedley Damien , Wells Sara , White Jacqueline K. , Wood Joshua A. ,   International Mouse Phenotyping Consortium, Murray Stephen A. , Heaney Jason D. , Nutter Lauryl M. J. 
Published: October 2021

AbstractThe International Mouse Phenotyping Consortium (IMPC) systematically produces and phenotypes mouse lines with presumptive null mutations to provide insight into gene function. The IMPC now uses the programmable RNA-guided nuclease Cas9 for its increased capacity and flexibility to efficiently generate null alleles in the C57BL/6N strain. In addition to being a valuable novel and accessible research resource, the production of 3,313 knockout mouse lines using comparable protocols provides a rich dataset to analyze experimental and biological variables affectingin vivogene engineering with Cas9. Mouse line production has two critical steps – generation of founders with the desired allele and germline transmission (GLT) of that allele from founders to offspring. A systematic evaluation of the variables impacting success rates identified gene essentiality as the primary factor influencing successful production of null alleles. Collectively, our findings provide best practice recommendations for using Cas9 to generate alleles in mouse essential genes, many of which are orthologs of genes linked to human disease.
Imbalance between IL-36 receptor agonist and antagonist drives neutrophilic inflammation in COPD
Authors: Baker Jonathan R , Fenwick Peter S , Koss Carolin K , Owles Harriet B , Elkin Sarah L , Thomas Matthew , Fine Jay , Kasmi Karim C El , Barnes Peter J , Donnelly Louise E 
Published: October 2021

AbstractCurrent treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating novel therapies. Here, we show that COPD patients have increased IL-36γ and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared to control subjects. IL-36γ is derived mainly from small airway epithelial cells (SAEC) and further induced by a viral mimetic, whereas IL-36RA is derived from macrophages. IL-36γ stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36γ thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, that was inhibited by exogenous IL-36RA. The use of a therapeutic antibody that inhibits binding to the IL-36 receptor (IL-36R) attenuated IL-36γ driven inflammation and cellular cross talk. We have demonstrated a novel mechanism for the amplification and propagation of neutrophilic inflammation in COPD and that blocking this cytokine family via a IL-36R neutralising antibody could be a promising new therapeutic strategy in the treatment of COPD.
Post translational modification of duplicated ribosomal protein paralogs promotes alternative translation and drug resistance
Authors: Malik-Ghulam Mustafa , Catala Mathieu , Scott Michelle S. , Elela Sherif Abou 
Published: October 2021

AbstractRibosomes are often seen as monolithic machines produced from uniformly regulated genes. However, in yeast most ribosomal proteins are produced from duplicated genes. Here, we demonstrate that gene duplications may serve as a stress response mechanism that modulates the global proteome through differential post-translational modification of ribosomal proteins paralogs. Our data indicate that the yeast paralog pair of the ribosomal protein L7/uL30 produces two differentially acetylated proteins. Under normal conditions most ribosomes incorporate the hypo-acetylated ‘major’ form favoring the translation of genes with short open reading frames. Exposure to drugs, on the other hand, increases the production of ribosomes carrying the hyper-acetylated minor paralog that increases translation of long reading frames. Many of these genes encode cell wall proteins that increase drug resistance in a programed change in translation equilibrium. Together the data reveal a mechanism of translation control through the differential fates of near-identical ribosomal protein isoforms.
Dramatic consequences of reducing erythrocyte membrane cholesterol on Plasmodium falciparum
Authors: Ahiya Avantika I. , Bhatnagar Suyash , Morrisey Joanne , Beck Josh R. , Vaidya Akhil B. 
Published: October 2021

AbstractCholesterol is the most abundant lipid in the erythrocyte. During its blood stage development, the malaria parasite establishes an active cholesterol gradient across the various membrane systems within the infected erythrocyte. Interestingly, some antimalarial compounds have recently been shown to disrupt cholesterol homeostasis in intraerythrocytic stages of Plasmodium falciparum. These studies point to the importance of cholesterol for parasite growth. Previously, reduction of cholesterol from the erythrocyte membrane by treatment with methyl-ß-cyclodextrin (MßCD) was shown to inhibit parasite invasion and growth. In addition, MßCD treatment of trophozoite stage P. falciparum was shown to result in parasite expulsion from the host cell. We have revisited these phenomena by using live video microscopy, ultrastructural analysis, and response to antimalarial compounds. By using time-lapse video microscopy of fluorescently tagged parasites, we show that MßCD treatment for just 30 min causes dramatic expulsion of the trophozoite stage parasites. This forceful expulsion occurs within 10 sec. Remarkably, the plasma membrane of the host cell from which the parasite has been expelled does not appear to be compromised. The parasitophorous vacuolar membrane (PVM) continued to surround the extruded parasite, but the PVM appeared damaged. Treatment with antimalarial compounds targeting PfATP4 or PfNCR1 prevented MßCD-mediated extrusion of the parasites, pointing to a potential role of cholesterol dynamics underlying the expulsion phenomena. We also confirmed the essential role of erythrocyte plasma membrane cholesterol for invasion and growth of P. falciparum. This defect can be partially complemented by cholesterol and desmosterol but not with epicholesterol, revealing stereospecificity underlying cholesterol function. Overall, our studies advance previous observations and reveal unusual cell biological features underlying cholesterol depletion of infected erythrocyte plasma membrane.ImportanceMalaria remains a major challenge in much of the world. Symptoms of malaria are caused by the growth of parasites belonging to Plasmodium spp. inside the red blood cells (RBC), leading to their destruction. The parasite depends upon its host for much of its nutritional need. Cholesterol is a major lipid in the RBC plasma membrane, which is the only source of this lipid for malarial parasites. We have previously shown that certain new antimalarial compounds disrupt cholesterol homeostasis in P. falciparum. Here we use live time-lapse video microscopy to show dramatic expulsion of the parasite from the host RBC when the cholesterol content of the RBC is reduced. Remarkably, this expulsion is inhibited by the antimalarials that disrupt lipid homeostasis. We also show stereospecificity of cholesterol in supporting parasite growth inside RBC. Overall, these results point to a critical role of cholesterol in physiology of malaria parasites.
The protein folding rate and the geometry and topology of the native state
Authors: Wang Jason , Panagiotou Eleni 
Published: October 2021

ABSTRACTProteins fold in 3-dimensional conformations which are important for their function. Characterizing the global conformation of proteins rigorously and separating secondary structure effects from topological effects is a challenge. New developments in Applied Knot Theory allow to characterize the topological characteristics of proteins (knotted or not). By analyzing a small set of two-state and multi-state proteins with no knots or slipknots, our results show that 95.4% of the analyzed proteins have non-trivial topological characteristics, as reflected by the second Vassiliev measure, and that the logarithm of the experimental protein folding rate depends on both the local geometry and the topology of the protein’s native state.
Severity of thermal burn injury is associated with systemic neutrophil activation
Authors: Laggner Maria , Lingitz Marie-Therese , Copic Dragan , Direder Martin , Klas Katharina , Bormann Daniel , Gugerell Alfred , Moser Bernhard , Radtke Christine , Hacker Stefan , Mildner Michael , Ankersmit Hendrik Jan , Haider Thomas 
Published: October 2021

AbstractObjectivesBurn injuries elicit a unique and dynamic stress response which can lead to burn injury progression. Though neutrophils represent crucial players in the burn-induced immunological events, the dynamic secretion pattern and systemic levels of neutrophil-derived factors have not been investigated in detail so far.MethodsSerum levels of neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone H3 (CitH3), and complement factor C3a were quantified in burn victims over 4 weeks post injury. Furthermore, the potential association with mortality, degree of burn injury, and inhalation trauma was evaluated. In addition, leukocyte, platelet, neutrophil, and lymphocyte counts were assessed. Lastly, we analyzed the association of neutrophil-derived factors with clinical severity scoring systems.ResultsSerum levels of NE, MPO, CitH3, and C3a were remarkably elevated in burn victims compared to healthy controls. Leukocyte and neutrophil counts were significantly increased on admission day and day 1, while relative lymphocytes were decreased in the first 7 days post burn trauma. Though neutrophil-derived factors did not predict mortality, patients suffering from 3rd degree burn injuries displayed increased CitH3 and NE levels. Accordingly, CitH3 and NE were elevated in cases with higher abbreviated burn severity indices (ABSI).ConclusionsTaken together, our data suggest a role for neutrophil activation and NETosis in burn injuries and burn injury progression. Targeting exacerbated neutrophil activation might represent a new therapeutic option for severe cases of burn injury.
Differential geometry methods for constructing manifold-targeted recurrent neural networks
Authors: Claudi Federico , Branco Tiago 
Published: October 2021

AbstractNeural computations can be framed as dynamical processes, whereby the structure of the dynamics within a neural network are a direct reflection of the computations that the network performs. A key step in generating mechanistic interpretations within thiscomputation through dynamicsframework is to establish the link between network connectivity, dynamics and computation. This link is only partly understood. Recent work has focused on producing algorithms for engineering artificial recurrent neural networks (RNN) with dynamics targeted to a specific goal manifold. Some of these algorithms only require a set of vectors tangent to the target manifold to be computed, and thus provide a general method that can be applied to a diverse set of problems. Nevertheless, computing such vectors for an arbitrary manifold in a high dimensional state space remains highly challenging, which in practice limits the applicability of this approach. Here we demonstrate how topology and differential geometry can be leveraged to simplify this task, by first computing tangent vectors on a low-dimensional topological manifold and then embedding these in state space. The simplicity of this procedure greatly facilitates the creation of manifold-targeted RNNs, as well as the process of designing task-solving on-manifold dynamics. This new method should enable the application of network engineering-based approaches to a wide set of problems in neuroscience and machine learning. Furthermore, our description of how fundamental concepts from differential geometry can be mapped onto different aspects of neural dynamics is a further demonstration of how the language of differential geometry can enrich the conceptual framework for describing neural dynamics and computation.
Fluorescence exclusion: a rapid, accurate and powerful method for measuring yeast cell volume
Authors: García-Ruano Daniel , Jain Akanksha , Ryan Joseph C. , Balasubramaniam Vasanthakrishnan Radhakrishnan , Venkova Larisa , Piel Matthieu , Coudreuse Damien 
Published: October 2021

ABSTRACTCells exist in an astonishing range of volumes across and within species. However, our understanding of cell size control remains limited, due in large part to the challenges associated with accurate determination of cell volume. Much of our comprehension of size regulation derives from models such as budding and fission yeast, but even for these morphologically stereotypical cells, assessment of cell volume has relied on proxies and extrapolations from two-dimensional measurements. Recently, the fluorescence exclusion method (FXm) was developed to evaluate the size of mammalian cells, but whether it could be applied to smaller cells remained unknown. Using specifically designed microfluidic chips and an improved data analysis pipeline, we show here that FXm reliably detects subtle difference in the volume of fission yeast cells, even for those with altered shapes. Moreover, it allows for the monitoring of dynamic volume changes at the single-cell level with high time resolution. Collectively, our work reveals how coupling FXm with yeast genetics will bring new insights into the complex biology of cell growth.SUMMARY STATEMENTFluorescence exclusion provides a unique method to accurately measure the volume of yeast cells at both the population and single-cell levels.
Laser heating system at the Extreme Conditions Beamline, P02.2, PETRA III
Authors: Konôpková Zuzana , Morgenroth Wolfgang , Husband Rachel , Giordano Nico , Pakhomova Anna , Gutowski Olof , Wendt Mario , Glazyrin Konstantin , Ehnes Anita , Delitz Jan Torben , Goncharov Alexander F. , Prakapenka Vitali B. , Liermann Hanns-Peter 
Published: October 2021

A laser heating system for samples confined in diamond anvil cells paired with in situ X-ray diffraction measurements at the Extreme Conditions Beamline of PETRA III is presented. The system features two independent laser configurations (on-axis and off-axis of the X-ray path) allowing for a broad range of experiments using different designs of diamond anvil cells. The power of the continuous laser source can be modulated for use in various pulsed laser heating or flash heating applications. An example of such an application is illustrated here on the melting curve of iron at megabar pressures. The optical path of the spectroradiometry measurements is simulated with ray-tracing methods in order to assess the level of present aberrations in the system and the results are compared with other systems, that are using simpler lens optics. Based on the ray-tracing the choice of the first achromatic lens and other aspects for accurate temperature measurements are evaluated.
Towards better library services: an investigation of factors affecting tourists’ satisfaction with “library + cultural tourism”
Authors: Pan Ying , Sun Lia H. , Yang Heqing , Zheng Jianming 
Published: October 2021

Purpose“Library + cultural tourism” (LCT) is a new direction for the sustainable development of libraries, but few scholars have researched it from a tourist perspective. The purpose of this paper is to identify what factors affect tourist satisfaction (TS) with LCT, reveal the interaction among these factors and provide strategies for better library services.Design/methodology/approachThis study collected 5,308 comments on Tianjin Binhai Library from three popular online travel communities. Grounded theory was adopted to identify what factors affect TS with LCT and reveal the interaction among these factors.FindingsThe results indicated that TS with LCT was affected by complex factors related to tour plans, tour expectations, cultural characteristics, environment, support services and emotions. Cultural characteristics, environment and support services were impacted by tour plans and tour expectations, which directly or indirectly affected TS mediated by emotions. TS further influenced their expectation of their next tour.Originality/valueThis paper uncovered critical problems with LCT using a case study of Tianjin Binhai Library. The results provide a reference for library practitioners to develop better library services for tourists and regular users/readers.
The relevance of relational capabilities in collaborative decisions
Authors: Della Corte Valentina , Aria Massimo , Del Gaudio Giovanna , Barney Jay Brian , Cobanoglu Cihan , Sepe Fabiana 
Published: October 2021

PurposeThis study aims to focus on inter-firm collaboration, exploring the main capabilities that can make a business more or less open to collaboration; it also considers the role of both firm-specific and relationship-specific capabilities. The paper proposes a model that can be used to study how the combination of the two categories of capabilities determines a firm’s approach to collaboration.Design/methodology/approachThrough a survey of high-end hotels in tourist destinations in Italy and the USA, this paper tests variable connected with firm-specific and relationship-specific aspects, using confirmatory factor analysis.FindingsFirms with greater capabilities are less open to cooperation; weaker firms with fewer resources appear to be more inclined to cooperate, probably to gain access to resources and competencies they do not possess.Research limitations/implicationsFrom a scientific perspective, this paper suggests an analysis based on both individual and relational capabilities when deciding whether to collaborate, while most studies based on a relational view just consider relational capabilities. The study could be enlarged to other countries and contexts.Practical implicationsFrom a practical perspective, it indicates the importance of accounting for different and sometimes diverging aspects when deciding to cooperate.Social implicationsIn terms of social implications, it shows that, apart from the relational capabilities they have, potential partners can decide not to collaborate.Originality/valueThe paper suggests a method of analyzing both individual and relational capabilities when deciding whether to engage in a collaboration. It shows that firms’ behavior does not necessarily depend on the firm’s relational capabilities.