bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention and management of behavioural and psychological symptoms in patients with dementia in acute care: a best practice implementation project
Authors: Akrour Rachid , Courret-Gilgen Catherine , Perrenoud Beatrice 
Published: July 2022

Abstract

Introduction:
Behavioural and psychological symptoms of dementia are very common in acute care. Agitation and aggressive behaviours are the most common symptoms and are challenging to manage. Early detection and a nonpharmacological approach are recommended.

Objectives:
To implement evidence-based recommendations for the prevention and management of aggression/agitation in patients with dementia in an acute geriatric care unit.

Methods:
The project used the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback tool. A baseline audit was conducted with seven audit criteria based on evidence summaries. It was followed by the implementation of an action plan and a follow-up audit.

Results:
Results showed moderate improvements in compliance with best practice recommendations. The second audit indicated an improvement up to 46% with the identification of factors/triggers that precipitate aggression/agitation and completion of a risk assessment. The highest improvement was the training of the nursing team (79%). Compliance with the involvement of patients and their families in the care planning improved slightly (14%). The lowest improvement was for the development and implementation of individualized care plans (10%).

Conclusion:
The project implementation achieved some positive changes. A formalized process for preventing aggression/agitation is in place. The interprofessional collaboration, the support given to the nursing team and the basket of nonpharmacological interventions were strengthened. The electronic documentation and a limited collaboration of the nursing team were challenging. As further strategies were implemented, further audit would be required to assess achievement in change and/or demonstration of improved care provided for this vulnerable population.
A linear DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain elicits protective immunity in domestic cats
Authors: Conforti Antonella , Sanchez Elisa , Salvatori Erika , Lione Lucia , Compagnone Mirco , Pinto Eleonora , Palombo Fabio , Sun Yuhua , Viscount Brian , Hayward James , Shorrock Clay , Diel Diego G. , Impellizeri Joseph A. , Aurisicchio Luigi 
Published: July 2022

ABSTRACTSince its first detection in China in late 2019, SARS-CoV-2, the etiologic agent of COVID-19 pandemic, has infected a wide range of animal species, especially mammals, all over the world. Indeed, as reported by the American Veterinary Medical Association, besides human-to-human transmission, human-to-animal transmission has been observed in some wild animals and pets, especially in cats. With animal models as an invaluable tool in the study of infectious diseases combined with the fact that the intermediate animal source of SARS-CoV-2 is still unknown, researchers have demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species. Here, we show results from a randomized Phase I/II clinical study conducted in domestic cats to assess safety and immunogenicity of a linear DNA (“linDNA”) vaccine encoding the RBD domain of SARS-CoV-2. No significant adverse events occurred and both RBD-specific binding/neutralizing antibodies and T cells were detected. These findings demonstrate the safety and immunogenicity of a genetic vaccine against COVID-19 administered to cats and strongly support the development of vaccines for preventing viral spread in susceptible species, especially those in close contact with humans.
The ‘Candidatus Phytoplasma mali’ effector protein SAP11CaPm interacts with MdTCP16, a class II CYC/TB1 transcription factor that is highly expressed during phytoplasma infection
Authors: Mittelberger Cecilia , Hause Bettina , Janik Katrin 
Published: July 2022

Abstract‘Candidatus Phytoplasma mali’, is a bacterial pathogen associated with the so-called apple proliferation disease in Malus × domestica. The pathogen manipulates its host with a set of effector proteins, among them SAP11CaPm, which shares similarity to SAP11AYWB from ‘Candidatus Phytoplasma asteris’. SAP11AYWB interacts and destabilizes the class II CIN transcription factors of Arabidopsis thaliana, namely AtTCP4 and AtTCP13 as well as the class II CYC/TB1 transcription factor AtTCP18, also known as BRANCHED1 being an important factor for shoot branching. It has been shown that SAP11CaPm interacts with the Malus × domestica orthologues of AtTCP4 (MdTCP25) and AtTCP13 (MdTCP24), but an interaction with MdTCP16, the orthologue of AtTCP18, has never been proven. The aim of this study was to investigate this potential interaction and close a knowledge gap regarding the function of SAP11CaPm. A Yeast two-hybrid test and Bimolecular Fluorescence Complementation in planta revealed that SAP11CaPm interacts with MdTCP16. MdTCP16 is known to play a role in the control of the seasonal growth of perennial plants and an increase of MdTCP16 gene expression has been detected in apple leaves in autumn. In addition to this, MdTCP16 is highly expressed during phytoplasma infection. Binding of MdTCP16 by SAP11CaPm might lead to the induction of shoot proliferation and early bud break, both of which are characteristic symptoms of apple proliferation disease.
Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021- January 2022
Authors: de Gier Brechje , van Asten Liselotte , Boere Tjarda M. , van Roon Annika , van Roekel Caren , Pijpers Joyce , van Werkhoven C.H. (Henri) , van den Ende Caroline , Hahné Susan J.M. , de Melker Hester E. , Knol Mirjam J. , van den Hof Susan 
Published: July 2022

AbstractBackgroundWe aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk of non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose.MethodsNational registries of causes of death, COVID-19 vaccination, specialized health care and long-term care reimbursements were linked by a unique person identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 5 or 8 weeks following a first, second or first booster dose, adjusting for birth year, sex, medical risk group and country of origin.ResultsVE against COVID-19 mortality was >90% for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80% at 7-8 months post-primary series for most groups, and around 60% for elderly receiving a high level of long-term care and for people aged 90+ years. Following a first booster dose, the VE increased to >85% in all groups. The risk of non-COVID-19 mortality was lower or similar in the 5 or 8 weeks following a first dose compared to no vaccination, as well as following a second dose compared to one dose and a booster compared to two doses, for all age and long-term care groups.ConclusionAt the population level, COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was observed.
Prevalence and predictors of Motoric Cognitive Risk syndrome in a community-dwelling older Scottish population: a longitudinal observational study
Authors: Mullin Donncha S. , Stirland Lucy E , Welstead Miles , Russ Tom C. , Luciano Michelle , Muniz-Terrera Graciela 
Published: July 2022

AbstractObjectivesThis study aimed to determine the prevalence of Motoric Cognitive Risk (MCR), describe associated risk factors for this syndrome, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults.MethodsA longitudinal prospective study using data from the Lothian Birth Cohort 1936 (LBC1936) and follow-up data from six, nine, and 12 years later. A total of 690 participants (mean [SD] age 76.3 [0.8] years) free from dementia were classified into non-MCR or MCR groups and baseline characteristics (age 69.5 [0.8] years) between the groups were compared.ResultsMCR prevalence rate ranged from 5.3-5.7% across the three waves. The presence of MCR was significantly associated with older age (six and nine years later), lower occupational socioeconomic status (six years later), and a range of tests of executive function (six, nine and 12 years later). Approximately 46% of the MCR group also had Mild Cognitive Impairment and almost all the MCR group had either Prefrailty or Frailty.ConclusionsThe prevalence of MCR in this Scottish cohort is lower than the pooled global average but higher than the prevalence in neighbouring countries. Future LBC1936 research should assess the risk factors associated with MCR to validate previous findings and analyse novel predictive factors, particularly socioeconomic status. This study can serve as a foundation for future studies to improve dementia risk assessments and potentially develop new interventions to reduce incident dementia.Key pointsMotoric Cognitive Risk (MCR) is a gait-based predementia syndrome that is quick, inexpensive, and practical to assess and diagnose, and it can identify individuals at high risk of developing dementiaThe prevalence of MCR in this older Scottish cohort ranged from 5.3-5.7% over three follow-up wavesFactors associated with MCR in this cohort include age, socioeconomic status and tests of executive functionThere is partial overlap between individuals with MCR and Mild Cognitive Impairment (MCI), but almost all individuals with MCR also had either Prefrailty or Frailty.
Single-nucleus resolution mapping of the adult C. elegans and its application to elucidate inter- and trans-generational response to alcohol
Authors: Truong Lisa , Chen Yen-Wei , Barrere-Cain Rio , Shuck Karissa , Xiao Wen , Levenson Max T. , da Veiga Beltrame Eduardo , Panter Blake , Reich Ella , Sternberg Paul W. , Yang Xia , Allard Patrick 
Published: July 2022

ABSTRACTSingle-cell RNA transcriptomic platforms have significantly contributed to our understanding of tissue heterogeneity as well as of developmental and cellular differentiation trajectories. They also provide an opportunity to map an organism’s response to environmental cues with high resolution and unbiasedly identify the cell types that are the most transcriptionally sensitive to exposures. Here, we applied single nucleus RNA-seq experimental and computational approaches to C. elegans to establish the transcriptome of the adult nematode and comprehensively characterize the transcriptional impact of ethanol as a model environmental exposure on the entire organism at cell type-resolution over several generations. Clustering, tissue and phenotype enrichment, and gene ontology analyses identified 31 clusters representing a diverse number of adult cell types, including those from syncytial and multi-nucleated tissues which are difficult to assess by single cell RNA-seq, such as the mitotic and meiotic germline, hypodermal cells, and the intestine. We applied this method to identify the impact of inter- and trans-generational exposure to two human-relevant doses of alcohol. Cell type proportions were not significantly altered by ethanol. However, Euclidean distance analysis identified several germline, striated muscle, and neuronal clusters as being major transcriptional targets of ethanol at both the F1 and F3 generations although the relative order of clusters changed between generations. The impact on germline clusters was further confirmed by phenotypic enrichment analysis as well as functional validation, namely a remarkable inter- and trans-generational increase in germline apoptosis, aneuploidy, and embryonic lethality. Together, snRNA-seq of the adult C. elegans represents a powerful approach for the detailed examination of an adult organism’s response to environmental cues.
Development of a first-in-class unimolecular dual GIP/GLP-2 analogue, GL-0001, for the treatment of bone fragility
Authors: Gobron Benoit , Couchot Malory , Irwin Nigel , Legrand Erick , Bouvard Béatrice , Mabilleau Guillaume 
Published: July 2022

ABSTRACTDue to ageing of the population, bone frailty is dramatically increasing worldwide. Although some therapeutic options exist, they do not fully protect or prevent against the occurrence of new fractures. All current drugs approved for the treatment of bone fragility target bone mass. However, bone resistance to fracture is not solely due to bone mass but relies also on bone ECM material properties, i.e. the quality of the bone matrix component. Here, we introduce the first-in-class unimolecular dual GIP/GLP-2 analogues, GL-0001, that activate simultaneously the glucose-dependent insulinotropic polypeptide receptor (GIPr) and the glucagon-like peptide-2 receptor (GLP-2r). GL-0001 acts synergistically through a cAMP-LOX pathway to enhance collagen maturity. Furthermore, in mice with ovariectomy-induced bone fragility, GL-0001 prevented excess trabecular bone degradation at the appendicular skeleton and also enhanced bone ECM material properties through reduction of the degree of mineralization and augmentation in enzymatic collagen crosslinking. These results demonstrate that targeting bone ECM material properties is a viable option to enhance bone strength and opens an innovative pathway for the treatment of patients suffering of bone fragility.
Contribution of Signaling Partner Association to Strigolactone Receptor Selectivity
Authors: Chen Jiming , Shukla Diwakar 
Published: July 2022

AbstractThe parasitic plant witchweed, or Striga hermonthica, results in agricultural losses of billions of dollars per year. It perceives its host via plant hormones called strigolactones, which acts as a germination stimulant for witchweed. Strigolactone signaling involves substrate binding to the strigolactone receptor followed by substrate hydrolysis and a conformational change from an inactive, or open state, to an active, or closed state. While in the active state, the receptor associates with a signaling partner, MAX2. Recently, it was shown that this MAX2 association process acts as a strong contributor to the uniquely high signaling activity observed in ShHTL7, however, it is unknown why ShHTL7 has enhanced MAX2 association affinity. Using an umbrella sampling molecular dynamics approach, we characterized the association processes of At D14, ShHTL7, a mutant of ShHTL7, and ShHTL6 with MAX2 homolog OsD3. From these results, we show that ShHTL7 has an enhanced standard binding free energy of OsD3 compared to the other receptors. Additionally, our results suggest that the overall topology of the T2-T3 helix region is likely an important modulator of MAX2 binding. Thus, differences in MAX2 association, modulated by differences in the T2-T3 helix region, are a contributor to differences in signaling activity between different strigolactone receptors.
Pressure-driven perfusion system to control, multiplex and recirculate cell culture medium for Organs-on-Chips
Authors: de Graaf Mees N. S. , Vivas Aisen , van der Meer Andries D. , Mummery Christine L. , Orlova Valeria V. 
Published: July 2022

AbstractOrgan-on-Chip (OoC) devices are increasingly used to mimic the tissue microenvironment of cells in intact organs. This includes microchannels to mimic, for example, fluidic flow through vessels. Present methods for controlling microfluidic flow in these systems rely on gravity, rocker systems or external pressure pumps. For many purposes, pressure pumps give the most consistent flow profiles but they are not well-suited for high throughput as might be required for testing drug responses. Here, we describe a method which allows multiplexing of microfluidic channels in OoC devices plus the accompanying custom software necessary to run the system. Moreover, we show the approach is also suited to for recirculation of culture medium, an essential cost consideration when expensive culture reagents are used that are not “spent” through uptake by the cells during transient unidirectional flow.
Diffusion MRI Head Motion Correction Methods are Highly Accurate but Impacted by Denoising and Sampling Scheme
Authors: Cieslak Matthew , Cook Philip A. , Tapera Tinashe M. , Radhakrishnan Hamsanandini , Elliott Mark , Roalf David R. , Oathes Desmond J. , Bassett Dani S. , Tisdall M. Dylan , Rokem Ariel , Grafton Scott T. , Satterthwaite Theodore D. 
Published: July 2022

ABSTRACTCorrecting head motion artifacts in diffusion-weighted MRI (dMRI) scans is particularly challenging due to the dramatic changes in image contrast at different gradient strengths and directions. Head motion correction is typically performed using a Gaussian Process model implemented in FSL’s Eddy. Recently, the 3dSHORE-based SHORELine method was introduced to correct any dMRI sequence that has more than one shell. Here we perform a comprehensive evaluation of both methods on realistic simulations of a software fiber phantom that provides known ground-truth head motion. We demonstrate that both methods perform remarkably well, but that performance can be impacted by sampling scheme, the pervasiveness of head motion, and the denoising strategy applied before head motion correction. Our study also provides an open and fully-reproducible workflow that could be used to accelerate evaluation studies of other dMRI processing methods in the future.HIGHLIGHTSBoth Eddy and SHORELine head motion correction methods performed quite well on a large variety of simulated dataDenoising with MP-PCA can improve head motion correction performance when Eddy is usedSHORELine effectively corrects motion in non-shelled acquisitions
The APE2 nuclease is essential for DNA double strand break repair by microhomology-mediated end-joining
Authors: Fleury Hubert , MacEachern Myles K. , Stiefel Clara M. , Anand Roopesh , Sempeck Colin , Nebenfuehr Benjamin , Dodd Benjamin , Taylor Erin , Dansoko Djelika , Ortega Raquel , Leung Justin W. , Boulton Simon J. , Arnoult Nausica 
Published: July 2022

SummaryMicrohomology-mediated end-joining (MMEJ) is an intrinsically mutagenic pathway of DNA double strand break repair essential for proliferation of homologous recombination (HR) deficient tumors. While targeting MMEJ has emerged as a powerful strategy to eliminate HR-deficient (HRD) cancers, this is limited by an incomplete understanding of the mechanism and factors required for MMEJ repair. Here, we identify the APE2 nuclease as a novel MMEJ effector. We show that loss of APE2 blocks the fusion of deprotected telomeres by MMEJ and inhibits MMEJ in DNA repair reporter assays to levels comparable to Pol Theta suppression. Mechanistically, we demonstrate that APE2 possesses intrinsic flap-cleaving activity, that its MMEJ function in cells depends on its nuclease domain and further identify uncharacterized domains required for recruitment to damaged DNA. We conclude that HR-deficient cells are addicted to APE2 due to a previously unappreciated role in MMEJ, which could be exploited in the treatment of cancer.
High-resolutionde novostructure prediction from primary sequence
Authors: Wu Ruidong , Ding Fan , Wang Rui , Shen Rui , Zhang Xiwen , Luo Shitong , Su Chenpeng , Wu Zuofan , Xie Qi , Berger Bonnie , Ma Jianzhu , Peng Jian 
Published: July 2022

AbstractRecent breakthroughs have used deep learning to exploit evolutionary information in multiple sequence alignments (MSAs) to accurately predict protein structures. However, MSAs of homologous proteins are not always available, such as with orphan proteins or fast-evolving proteins like antibodies, and a protein typically folds in a natural setting from its primary amino acid sequence into its three-dimensional structure, suggesting that evolutionary information and MSAs should not be necessary to predict a protein’s folded form. Here, we introduce OmegaFold, the first computational method to successfully predict high-resolution protein structure from a single primary sequence alone. Using a new combination of a protein language model that allows us to make predictions from single sequences and a geometry-inspired transformer model trained on protein structures, OmegaFold outperforms RoseTTAFold and achieves similar prediction accuracy to AlphaFold2 on recently released structures. OmegaFold enables accurate predictions on orphan proteins that do not belong to any functionally characterized protein family and antibodies that tend to have noisy MSAs due to fast evolution. Our study fills a much-encountered gap in structure prediction and brings us a step closer to understanding protein folding in nature.
ZAXINONE SYNTHASE 2 regulates growth and arbuscular mycorrhizal symbiosis in rice
Authors: Ablazov Abdugaffor , Votta Cristina , Fiorilli Valentina , Wang Jian You , Aljedaani Fatimah , Jamil Muhammad , Balakrishna Aparna , Balestrini Raffaella , Liew Kit Xi , Rajan Chakravarthy , Berqdar Lamis , Blilou Ikram , Lanfranco Luisa , Al-Babili Salim 
Published: July 2022

AbstractCarotenoid cleavage, catalyzed by CAROTENOID CLEAVAGE DIOXYGENASES (CCDs), provides signaling molecules and precursors of plant hormones. Recently, we showed that zaxinone, a novel apocarotenoid metabolite formed by the CCD Zaxinone Synthase (ZAS), is a growth regulator required for normal rice growth and development. The rice genome encodes three OsZAS homologs, called here OsZAS1b, OsZAS1c, and OsZAS2, with unknown functions. Here, we investigated the enzymatic activity, expression pattern, and subcellular localization of OsZAS2, and generated and characterized loss-of-function CRISPR/Cas9-Oszas2 mutants. We show that OsZAS2 formed zaxinone in vitro. OsZAS2 is a plastid-localized enzyme mainly expressed in the root cortex under phosphate starvation. Moreover, OsZAS2 expression increased during mycorrhization, specifically in arbuscule-containing cells. Oszas2 mutants contained lower zaxinone content in roots and exhibited reduced root and shoot biomass, less productive tiller, and higher strigolactone (SL) levels. Exogenous zaxinone application repressed SL biosynthesis and partially rescued the growth retardation of Oszas2 mutant. Consistent with the OsZAS2 expression pattern, Oszas2 mutants displayed a lower frequency of AM colonization. In conclusion, OsZAS2 encodes a further zaxinone-forming enzyme that determines rice growth and architecture and strigolactone content and is required for optimal mycorrhization.