bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Beyond Places of Safety’ – a qualitative study exploring the implementation of mental health crisis care innovations across England
Authors: Foye Una , Appleton Rebecca , Nyikavaranda Patrick , Lyons Natasha , Dare Ceri , Lynch Chris , Persaud Karen , Ahmed Nafiso , Stuart Ruth , Schlief Merle , Huong Xia , Sevdalis Nick , Sheridan-Rains Luke , Rojas-Garcia Antonio , Stefan Martin , Clark Jeremy , Simpson Alan , Johnson Sonia , Lloyd-Evans Brynmor 
Published: January 2023

AbstractBackgroundMental health acute and crisis care consumes a large share of mental health budgets internationally but is often experienced as unsatisfactory and difficult to access. As a result, there is an increasing move towards developing innovative community crisis services, to improve patient experience and relieve pressure on inpatient and emergency services. This study aims to understand what helps and hinders the implementation of innovative mental health crisis care projects in England.MethodsUsing a qualitative approach, 18 interviews were conducted with crisis care service managers exploring their experiences and views of the development and implementation of their service developed with support from an English national capital funding programme. A framework analysis was conducted informed by implementation science.ResultsKey facilitators to implementation of innovative crisis services included bottom-up development, service user involvement, strong collaborative working, and leadership and management buy-in. Key barriers that affected the projects implementation included the complexities of crisis care, workforce challenges and resourcing issues.ConclusionThere is a recognised need to improve, update, and innovate current crisis care offers. Results from this study suggest that a range of models can help address the heterogenous needs of local populations and that such services can be successfully implemented where they utilise a whole-systems approach, involving service users and relevant professional stakeholders beyond mental health services in planning and developing the service.
Prior SARS-CoV-2 Infection and COVID-19 Vaccine Effectiveness against Outpatient Illness during Widespread Circulation of SARS-CoV-2 Omicron Variant, US Flu VE Network
Authors: Tartof Sara Y. , Xie Fagen , Yadav Ruchi , Wernli Karen J. , Martin Emily T. , Belongia Edward A. , Gaglani Manjusha , Zimmerman Richard K. , Talbot H. Keipp , Thornburg Natalie , Flannery Brendan , Chung Jessie R. ,   US Flu VE Network Investigators
Published: January 2023

AbstractBackgroundWe estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI).MethodsDuring SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status.Results455 (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%– 99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%–76%) against Omicron; VE against Delta could not be estimated.ConclusionsThree mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants.
Pathogenic accumulation of T follicular helper cells in lupus disease depends on PD-L1 and IL-4 expressing basophils
Authors: Tchen John , Simon Quentin , Chapart Léa , Lamri Yasmine , Saidoune Fanny , Pacreau Emeline , Pellefigues Christophe , Bex-Coudrat Julie , Karasuyama Hajime , Miyake Kensuke , Hidalgo Juan , Fallon Padraic G. , Papo Thomas , Blank Ulrich , Benhamou Marc , Hanouna Guillaume , Sacre Karim , Daugas Eric , Charles Nicolas 
Published: January 2023

ABSTRACTSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies raised against nuclear antigens and whose production is promoted by autoreactive T follicular helper (TFH) cells. Basophils, by accumulating in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms to be defined. Here, we demonstrate that a functional relationship between TFH cells and basophils occurs in SLO during lupus pathogenesis. On SLE patient blood basophils, PD-L1 expression was upregulated and associated with TFH and TFH2 cell expansions and with disease activity. In two distinct lupus-like mouse models, TFH cell pathogenic accumulation, maintenance and function, and disease activity were dependent on basophils and their expressions of PD-L1 and IL-4. Our study establishes a direct link between basophils and TFH cells in the SLE context that promotes autoreactive IgG production and lupus nephritis pathogenesis. Altering the basophil/TFH cell axis in the SLE context may represent a promising innovative intervention strategy in SLE.
ADAPTIVE TIME LOCATION SAMPLING FOR COMPASS, A SARS-COV-2 PREVALENCE STUDY IN FIFTEEN DIVERSE COMMUNITIES IN THE UNITED STATES
Authors: Zangeneh Sahar Z , Skalland Timothy , Yuhas Krista , Emel Lynda , De Dieu Tapsoba Jean , Reed Domonique , Amos Christopher I. , Donnell Deborah , Moore Ayana , Justman Jessica ,   the CoVPN 5002 Study Team
Published: January 2023

ABSTRACTThe COVPN 5002 (COMPASS) study aimed to estimate the prevalence of SARS-CoV-2 (active SARS-CoV-2 or prior SARS-CoV-2 infection) in children and adults attending public venues in 15 socio-demographically diverse communities in the United States. To protect against potential challenges in implementing traditional sampling strategies, time-location sampling (TLS) using complex sampling involving stratification, clustering of units, and unequal probabilities of selection was used to recruit individuals from neighborhoods in selected communities. The innovative design adapted to constraints such as closure of venues; changing infection hotspots; and uncertain policies. Recruitment of children and the elderly raised additional challenges in sample selection and implementation. To address these challenges, the TLS design adaptively updated both the sampling frame and the selection probabilities over time using information acquired from prior weeks. Although the study itself was specific to COVID-19, the strategies presented in this paper could serve as a case study that can be adapted for performing rigorous population-level inferences in similar settings and could help inform rapid and effective responses to future global public health challenges.
ODNA: Identification of Organellar DNA by Machine Learning
Authors: Martin Roman , Nguyen Minh Kien , Lowack Nick , Heider Dominik 
Published: January 2023

MotivationIdentifying organellar DNA, such as mitochondrial or plastid sequences, inside a whole genome assembly, remains challenging and requires biological background knowledge. To address this, we developed ODNA based on genome annotation and machine learning to fulfill.ResultsODNA is a software that performs organellar DNA sequence classification of a genome assembly by machine learning based on a pre-defined genome annotation workflow. We trained our model with 829,769 DNA sequences from 405 genome assemblies and achieved very high predictive performance (e.g., MCC of 0.61) on independent validation data, thus outperforming existing approaches significantly.AvailabilityOur software ODNA is freely accessible as a web service athttps://odna.mathematik.uni-marburg.deand can also be run in a docker container. The source code can be found athttps://gitlab.com/mosga/odnaand the processed data at Zenodo (DOI: 10.5281/zenodo.7506483).
Smooth Muscle Cell Death Drives an Osteochondrogenic Phenotype and Severe Proximal Vascular Disease in Progeria
Authors: Murtada Sae-Il , Kawamura Yuki , Cavinato Cristina , Wang Mo , Ramachandra Abhay B. , Spronck Bart , Tellides George , Humphrey Jay D. 
Published: January 2023

ABSTRACTHutchinson-Gilford Progeria Syndrome results in rapid aging and severe cardiovascular sequelae that accelerate near end of life. We associate progressive deterioration of arterial structure and function with single cell transcriptional changes, which reveals a rapid disease process in proximal elastic arteries that largely spares distal muscular arteries. These data suggest a novel sequence of progressive vascular disease in progeria: initial extracellular matrix remodeling followed by mechanical stress-induced smooth muscle cell death in proximal arteries, leading a subset of remnant smooth muscle cells to an osteochondrogenic phenotypic modulation that results in an accumulation of proteoglycans that thickens the wall and increases pulse wave velocity, with late calcification exacerbating these effects. Increased pulse wave velocity drives left ventricular diastolic dysfunction, the primary diagnosis in progeria children. Mitigating smooth muscle cell loss / phenotypic modulation promises to have important cardiovascular implications in progeria patients.
Origin Matters: Using a Local Reference Genome Improves Measures in Population Genomics
Authors: Thorburn Doko-Miles J. , Sagonas Kostas , Binzer-Panchal Mahesh , Chain Frederic J.J. , Feulner Philine G.D. , Bornberg-Bauer Erich , Reusch Thorsten BH , Samonte-Padilla Irene E. , Milinski Manfred , Lenz Tobias L. , Eizaguirre Christophe 
Published: January 2023

AbstractGenome-level sequencing enables us to ask fundamental questions about the genetic basis of adaptation, population structure, and epigenetic mechanisms, but usually requires a suitable reference genome for mapping population-level re-sequencing data. In some model systems, multiple reference genomes are available, giving researchers the challenging task of determining which reference genome best suits their data. Here we compare the use of two different reference genomes for the three-spined stickleback (Gasterosteus aculeatus), one novel genome derived from a European gynogenetic individual and the published reference genome of a North American individual. Specifically, we investigate the impact of using a local reference versus one generated from a distinct lineage on several common population genomics analyses. Through mapping genome resequencing data of 60 sticklebacks from across Europe and North America, we demonstrate that genetic distance among samples and the reference impacts downstream analyses. Using a local reference genome increased mapping efficiency and genotyping accuracy, effectively retaining more and better data. Despite comparable distributions of the metrics generated across the genome using SNP data (i.e., π, Tajima’sD, andFST), window-based statistics using different references resulted in different outlier genes and enriched gene functions. A marker-based analysis of DNA methylation distributions had a comparably high overlap in outlier genes and functions, yet with distinct differences depending on the reference genome. Overall, our results highlight how using a local reference genome decreases reference bias to increase confidence in downstream analyses of the data. Such results have significant implications in all reference-genome-based population genomic analyses.
The identification and analysis of meristematic mutations within the apple tree that developed theRubyMacsport mutation
Authors: Sun Hequan , Abeli Patrick , Campoy José Antonio , Rütjes Thea , Krause Kristin , Jiao Wen-Biao , Korff Maria von , Beaudry Randy , Schneeberger Korbinian 
Published: January 2023

ABSTRACTUnderstanding the molecular basis of sport mutations in fruit trees can accelerate breeding of novel cultivars. For this, we analyzed the DNA of the apple tree that evolved theRubyMacphenotype through a sport mutation that introduced changes in fruit coloration in upper branches of the tree. Unexpectedly, we not only found 46de novomutations, but also 54 somatic gene conversions (i.e., loss-of-heterozygosity mutations) distinguishing the mutant and wild-type branches of the tree. Approximately 30% of thede novomutations and 80% of the gene conversions were observed only in specific cells layers suggesting that they occurred in the corresponding meristematic layers. Interestingly, thede novomutations were enriched for GC=>AT transitions, while the gene conversions showed the opposite bias for AT=>GC transitions suggesting that GC-biased gene conversions have the potential to counteract the AT-bias ofde novomutations. By comparing the gene expression patterns in fruit skins from mutant and wild-type branches, we found 56 differentially expressed genes including 18 that were involved in anthocyanin biosynthesis. While none of the differently expressed genes harbored a mutation, we found that some of the mutations affected the integrity of candidate genes in regions of the genome that were recently associated with natural variation in fruit coloration.
CellCharter reveals spatial cell niches associated with tissue remodeling and cell plasticity
Authors: Varrone Marco , Tavernari Daniele , Santamaria-Martínez Albert , Walsh Logan A. , Ciriello Giovanni 
Published: January 2023

ABSTRACTTissues are organized in cellular niches, the composition and interactions of which can be investigated using spatial omics technologies. However, systematic analyses of tissue composition are challenged by the scale and diversity of the data. Here we present CellCharter, an algorithmic framework to identify, characterize, and compare cellular niches in spatially resolved datasets. CellCharter outperformed existing approaches and effectively identified cellular niches across datasets generated using different technologies, and comprising hundreds of samples and millions of cells. In multiple human lung cancer cohorts, CellCharter uncovered a cellular niche composed of tumor-associated neutrophils and cancer cells expressing markers of hypoxia and cell migration. This cancer cell state was spatially segregated from more proliferative tumor cell clusters and was associated with tumor-associated neutrophil infiltration and poor prognosis in independent patient cohorts. Overall, CellCharter enables systematic analyses across data types and technologies to decode the link between spatial tissue architectures and cell plasticity.
Intrinsic microtubule destabilization of multiciliated choroid plexus epithelial cells during postnatal lifetime
Authors: Ho Kim Hoa , Scarpetta Valentina , Salio Chiara , D’Este Elisa , Meschkat Martin , Wurm Christian A. , Kneussel Matthias , Janke Carsten , Magiera Maria M. , Sassoè-Pognetto Marco , Brill Monika S. , Patrizi Annarita 
Published: January 2023

AbstractChoroid plexus (ChP) epithelium is composed of specialized multiciliated cells. By using multiple microscopic techniques, biochemical approaches in various mutant mice and longitudinal analysis from mouse embryogenesis to aging, we show that ChP cilia are built on a gradient of events which are spatio-temporally regulated. We uncover that ChP cilia develop prenatally since early tissue morphogenesis, and proceeds as a multi-step process characterized by basal body multiplication and axoneme formation directly at the apical cellular compartment. Our data also show that choroid plexus cilia contain both primary and motile features. Remarkably, we demonstrate that ChP cilia undergo axoneme resorption, starting from early youth, through a tubulin destabilization process, which is primarily controlled by polyglutamylation levels and could be mitigated by the removal of the microtubule-severing enzyme spastin. Notably, we demonstrate that this phenotype is preserved in human samples.
A chromosome-scale assembly for tetraploid sour cherry (Prunus cerasusL.) ‘Montmorency’ identifies three distinct ancestralPrunusgenomes
Authors: Goeckeritz Charity Z. , Rhoades Kathleen E. , Childs Kevin L. , Iezzoni Amy F. , VanBuren Robert , Hollender Courtney A. 
Published: January 2023

AbstractBackgroundSour cherry (Prunus cerasusL.) is a valuable fruit crop in the Rosaceae family and a hybrid between progenitors most closely related to extantP. fruticosa(ground cherry) andP. avium(sweet cherry). Sour cherry is an allotetraploid with few genomic resources, so a genome sequence would greatly facilitate the improvement of this crop. InPrunus, two known classes of genes are of particular importance to breeding strategies: the self-incompatibility loci (S-alleles), which determine compatible crosses and are critically important for successful fertilization and fruit set, and the Dormancy Associated MADS-box genes (DAMs), which strongly affect dormancy transitions and flowering time.ResultsHere we report a chromosome-scale genome assembly for sour cherry cultivar ‘Montmorency’, the predominant sour cherry cultivar grown in the U.S. We also generated a draft assembly ofP. fruticosato use alongside a publishedP. aviumsequence for syntelog-based subgenome assignments for ‘Montmorency’. Using hierarchal k-mer clustering and phylogenomics, we provide compelling evidence this allotetraploid is trigenomic, containing two distinct subgenomes inherited from aP. fruticosa-likeancestor (A and A’) and two copies of the same subgenome inherited from aP. avium-likeancestor (BB). We therefore assigned the genome composition of ‘Montmorency’ to be AA’BB and show little to no recombination has occurred between progenitor subgenomes (A/A’ and B). TheS-alleles and DAMs in ‘Montmorency’ andP. fruticosawere manually annotated and demonstrated to support the three subgenome assignments. Lastly, the hybridization event that ‘Montmorency’ is descended from was estimated to have occurred less than 1.61 million years ago, making sour cherry a relatively recent allotetraploid.ConclusionsThe genome of sour cherry cultivar Montmorency highlights the evolutionary complexity of the genusPrunus. These genomic resources will inform future breeding strategies for sour cherry, comparative genomics in the Rosaceae, and questions regarding neopolyploidy.
Firing-rate-modulated spike detection and neural decoding co-design
Authors: Zhang Zheng , Constandinou Timothy G. 
Published: January 2023

AbstractObjectiveTranslational efforts on spike-signal-based implantable brain-machine interfaces (BMIs) are increasingly aiming to minimise bandwidth while maintaining decoding performance. Developing these BMIs requires advances in neuroscience and electronic technology, as well as using low-complexity spike detection algorithms and high-performance machine learning models. While some state-of-the-art BMI systems jointly design spike detection algorithms and machine learning models, it remains unclear how the detection performance affects decoding.ApproachWe propose the co-design of the neural decoder with an ultra-low complexity spike detection algorithm. The detection algorithm is designed to attain a target firing rate, which the decoder uses to modulate the input features preserving statistical invariance.Main resultsWe demonstrate a multiplication-free fixed-point spike detection algorithm with nearly perfect detection accuracy and the lowest complexity among studies we have seen. By co-designing the system to incorporate statistically invariant features, we observe significantly improved long-term stability, with decoding accuracy degrading by less than 10% after 80 days of operation. Our analysis also reveals a nonlinear relationship between spike detection and decoding performance. Increasing the detection sensitivity improves decoding accuracy and long-term stability, which means the activity of more neurons is beneficial despite the detection of more noise. Reducing the spike detection sensitivity still provides acceptable decoding accuracy whilst reducing the bandwidth by at least 30%.SignificanceOur findings regarding the relationship between spike detection and decoding performance can provide guidance on setting the threshold for spike detection rather than relying on training or trial-and-error. The trade-off between data bandwidth and decoding performance can be effectively managed using appropriate spike detection settings. We demonstrate improved decoding performance by maintaining statistical invariance of input features. We believe this approach can motivate further research focused on improving decoding performance through the manipulation of data itself (based on a hypothesis) rather than using more complex decoding models.
Retroviral infection and commensal bacteria dependently alter the metabolomic profile in a sterile organ
Authors: Spring Jessica , Beilinson Vera , DeFelice Brian C. , Sanchez Juan M. , Fischbach Michael , Chervonsky Alexander , Golovkina Tatyana 
Published: January 2023

AbstractBoth viruses and bacteria produce ‘pathogen associated molecular patterns’ that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites while viruses could change metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of Murine Leukemia Virus-infected mice monocolonized withLactobacillus murinusto show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus, open a new avenue for future investigations.
Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the Glucocorticoid Receptor
Authors: Noddings Chari M. , Johnson Jill L. , Agard David A. 
Published: January 2023

AbstractHsp90 is an essential molecular chaperone responsible for the folding and activation of hundreds of ‘client’ proteins, including the glucocorticoid receptor (GR)1-3. Previously, we revealed that GR ligand binding activity is inhibited by Hsp70 and restored by Hsp90, aided by co-chaperones4. We then presented cryo-EM structures mechanistically detailing how Hsp70 and Hsp90 remodel the conformation of GR to regulate ligand binding5,6.In vivo, GR-chaperone complexes are found associated with numerous Hsp90 co-chaperones, but the most enigmatic have been the immunophilins FKBP51 and FKBP52, which further regulate the activity of GR and other steroid receptors7-9. A molecular understanding of how FKBP51 and FKBP52 integrate with the GR chaperone cycle to differentially regulate GR activationin vivois lacking due to difficulties reconstituting these interactions. Here, we present a 3.01 Å cryo-EM structure of the GR:Hsp90:FKBP52 complex, revealing, for the first time, that FKBP52 directly binds to the folded, ligand-bound GR using three novel interfaces, each of which we demonstrate are critical for FKBP52-dependent potentiation of GR activityin vivo. In addition, we present a 3.23 Å cryo-EM structure of the GR:Hsp90:FKBP51 complex, which, surprisingly, largely mimics the GR:Hsp90:FKBP52 structure. In both structures, FKBP51 and FKBP52 directly engage the folded GR and unexpectedly facilitate release of p23 through an allosteric mechanism. We also reveal that FKBP52, but not FKBP51, potentiates GR ligand bindingin vitro, in a manner dependent on FKBP52-specific interactions. Altogether, we reveal how FKBP51 and FKBP52 integrate into the GR chaperone cycle to advance GR to the next stage of maturation and how FKBP51 and FKBP52 compete for GR:Hsp90 binding, leading to functional antagonism.