bluuebunny/crossref_metadata_2025_split huggingface dataset:
ProbeTools: Designing hybridization probes for targeted genomic sequencing of diverse and hypervariable viral taxa
Authors: Kuchinski Kevin S. , Duan Jun , Himsworth Chelsea , Hsiao William , Prystajecky Natalie A. 
Published: February 2022

ABSTRACTBackgroundSequencing viruses in many specimens is hindered by excessive background material from hosts, microbiota, and environmental organisms. Consequently, enrichment of target genomic material is necessary for practical high-throughput viral genome sequencing. Hybridization probes are widely used for enrichment in many fields, but their application to viral sequencing faces a major obstacle: it is difficult to design panels of probe oligo sequences that broadly target many viral taxa due to their rapid evolution, extensive diversity, and genetic hypervariability. To address this challenge, we created ProbeTools, a package of bioinformatic tools for generating effective viral capture panels, and for assessing coverage of target sequences by probe panel designs in silico. In this study, we validated ProbeTools by designing a panel of 3,600 probes for subtyping the hypervariable haemagglutinin (HA) and neuraminidase (NA) genome segments of avian-origin influenza A viruses (AIVs). Using in silico assessment of AIV reference sequences and in vitro capture on egg-cultured viral isolates, we demonstrated effective performance by our custom AIV panel and ProbeTools’ suitability for challenging viral probe design applications.ResultsBased on ProbeTool’s in silico analysis, our panel provided broadly inclusive coverage of 14,772 HA and 11,967 NA reference sequences. 90% of these HA and NA references sequences had 90.8% and 95.1% of their nucleotide positions covered in silico by the panel respectively. We also observed effective in vitro capture on a representative collection of 23 egg-cultured AIVs that included isolates from wild birds, poultry, and humans and representatives from all HA and NA subtypes. 42 of 46 HA and NA segments had over 98.3% of their nucleotide positions significantly enriched by our custom panel. These in vitro results were further used to validate ProbeTools’ in silico coverage assessment algorithm; 89.2% of in silico predictions were concordant with in vitro results.ConclusionsProbeTools generated an effective panel for subtyping AIVs that can be deployed for genomic surveillance, outbreak prevention, and pandemic preparedness. Effective probe design against hypervariable AIV targets also validated ProbeTools’ design and coverage assessment algorithms, demonstrating their suitability for other challenging viral capture applications.
Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
Authors: Starr Tyler N. , Greaney Allison J. , Hannon William W. , Loes Andrea N. , Hauser Kevin , Dillen Josh R. , Ferri Elena , Farrell Ariana Ghez , Dadonaite Bernadeta , McCallum Matthew , Matreyek Kenneth A. , Corti Davide , Veesler David , Snell Gyorgy , Bloom Jesse D. 
Published: February 2022

AbstractSARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single amino-acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently N501Y, cause epistatic shifts in the effects of mutations at other sites, thereby shaping subsequent evolutionary change. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.
Impact of body mass index on 5-year survival rates in patients undergoing allogeneic hematopoietic stem cell transplantation
Authors: Aoyama Takashi , Notsu Akifumi , Ichimaru Koki , Tsuji Masanori , Yoshitsugu Kanako , Fukaya Masafumi , Enami Terukazu , Ikeda Takashi 
Published: February 2022

AbstractBackgroundThe association between cancer survival and body mass index (BMI) has been elucidated. However, the impact of patients’ baseline characteristics on allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes remains unclear.ObjectivesTo examine the baseline clinical factors associated with 5-year survival rates in patients undergoing allo-HSCT.Study designThis was a retrospective exploratory observational study. Patients (n=113, average age: 55 years; 52 women) who underwent allo-HSCT at the Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, between January 2008 and March 2015 were included in this study.ResultsThe 5-year survival rate (65%) was associated with the baseline geriatric nutritional risk index (GNRI; odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.03–1.36, P <0.01) and the BMI (OR=1.06, 95% CI: 1.02–1.12, P <0.01). The cut-off values for BMI and GNRI were 20.5 kg/m2 and 101 points, respectively (area under the curve, 0.65017 and 0.67637, respectively). The 5-year survival rate was poorer for patients with sarcopenia (41.5%) than for those without sarcopenia prior to allo-HSCT (p=0.05).ConclusionsBMI and GNRI values before allo-HCST pre-treatment were independent predictors of the 5-year survival rates. Patients undergoing allo-HSCT may require nutritional interventions during pre-treatment to reduce the risk of sarcopenia, which affects their survival rates.
Self-management of depression and anxiety amongst frail older adults in the United Kingdom: a qualitative study
Authors: Nair Pushpa , Walters Kate R. , Aw Su , Gould Rebecca L. , Kharicha Kalpa , Buszewicz Marta , Frost Rachael 
Published: February 2022

AbstractObjectivesDepression and anxiety are common in frail older people and are associated with high levels of morbidity and mortality, yet they typically face greater barriers to accessing mental health treatments than younger people and express preferences for self-managing their symptoms. This study aims to explore frail older adults’ experiences of self-managing symptoms of depression and/or anxiety.DesignQualitative semi-structured interviews, exploring experiences of depression and/or anxiety, ways participants self-managed these and the contexts within which this took place. Interviews were audio-recorded and transcribed verbatim.Participants28 frail older adults in the United Kingdom, purposively sampled for neighbourhood, frailty and symptoms of anxiety/depression.AnalysisThematic analysis to inductively derive themes from the data.ResultsOur findings suggest that frail older adults find maintaining routines, engaging in meaningful and creative activities and socialising important to self-manage depression and anxiety. These could all be adapted to the level of frailty experienced. Stoicism, acceptance, faith or addressing the perceived cause were helpful in some situations and for some personalities. Distraction and avoidance were helpful for more severe symptoms or where the causes of symptoms could not be resolved. Self-management strategies were less well-established for anxiety symptoms, especially when linked to newer health fears and worries about the future.ConclusionsDeveloping services and sources of information that support and facilitate key therapeutic components of self-management, which align with older adults’ preferred coping styles and take into account levels of frailty, may be a way of supporting frail older people waiting for mental health treatments or those who prefer not to access these. Greater awareness of anxiety and how it can be self-managed in frail older people is needed.
A Novel Home-Based Study of Circadian Rhythms: Design, Rationale, and Methods for the Circadia Study
Authors: Vlasac Irma , Bormes Gregory , Do Elizabeth , Benkhoukha Selma , Diallo Naby , Fryou Noah L. , Gioia Siena , Joseph Clarence , Kuan Anne , Lapan Jennifer , Oluwadara David ,   the Pepper Team, Saxena Richa , Scheer Frank , Woodson Faraji , Lane Jacqueline 
Published: February 2022

AbstractThe Circadia Study (Circadia) is a novel “direct to participant” research study investigating the genetics of circadian rhythm disorders. The long-term goals of this study are to better understand the genetics of circadian rhythm disorders, investigate the efficacy and accessibility of an at-home, self-directed DLMO collection, to improve health outcomes in the future for patients with circadian rhythm disorders, and to address the specific needs of the circadian rhythm disorder patient population.In this manuscript, we briefly outline the standard methods of both circadian biology research protocols and circadian rhythm disorder diagnostic procedures. We describe some of the inherent limitations of current circadian research and diagnostic methods, which motivated our development of and informed the design of the Circadia Study. We discuss the main goals of the Circadia Study, and we outline key features of our study design that build upon current study methods and address limitations. Finally, we describe specific aspects of the Circadia Study, including our study population, data collection methods, and standard operating procedures so that others may replicate aspects of the study design.The Circadia Study is approved for human subject research by the Mass General Brigham Institutional Review Board, Protocol # 2020P002779.
Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study
Authors: Ge Jin , Digitale Jean C. , Pletcher Mark J. , Lai Jennifer C. ,   the N3C Consortium
Published: February 2022

AbstractBackground and AimsThe incidence and outcomes of breakthrough SARS-CoV-2 infections in vaccinated chronic liver disease (CLD) patients have not been well-characterized in non-veteran populations. We used the National COVID Cohort Collaborative (N3C), a dataset of 10.7 million patients, of whom 0.9 million have vaccination data, to describe outcomes in vaccinated CLD patients.MethodsWe identified all CLD patients with or without cirrhosis regardless of vaccination status who had SARS-CoV-2 testing in the N3C Data Enclave as of 1/15/2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients.ResultsWe isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of the 43,079 vaccinated CLD patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) were with cirrhosis. Estimated incidence rates for breakthrough infections were 5.6 and 5.1 per 1,000 person-months for 27,235 fully vaccinated CLD patients without cirrhosis and for 8,218 fully vaccinated CLD patients with cirrhosis, respectively.Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis in our cohort, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The combined 30-day all-cause rate of mechanical ventilation (without death) or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days.ConclusionsIn this N3C Data Enclave study, breakthrough infection rates were similar amongst CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality among CLD patients with cirrhosis after infection. These results provide an additional impetus for increasing vaccination uptake among patients with severe liver disease.
Multimodal MRI examination of structural and functional brain changes in older women with breast cancer in the first year of antiestrogen hormonal therapy
Authors: McDonald Brenna C. , Van Dyk Kathleen M. , Deardorff Rachael L. , Bailey Jessica N. , Zhai Wanting , Carroll Judith E. , Root James C. , Ahles Tim A. , Mandelblatt Jeanne S. , Saykin Andrew J. 
Published: March 2022

AbstractPurposeCancer patients are concerned about treatment-related cognitive problems. We examined effects of antiestrogen hormonal therapy on brain imaging metrics in older women with breast cancer.MethodsWomen aged 60+ treated with hormonal therapy only and matched non-cancer controls (n=29/group) completed MRI and objective and self-reported cognitive assessment at pre-treatment/enrollment and 12 months later. Gray matter was examined using voxel-based morphometry (VBM), FreeSurfer, and brain age calculations. Functional MRI (fMRI) assessed working memory-related activation. Analyses examined cross-sectional and longitudinal differences and tested associations between brain metrics, cognition, and days on hormonal therapy.ResultsThe cancer group showed regional reductions over 12 months in frontal, temporal, and parietal gray matter on VBM, reduced FreeSurfer cortical thickness in prefrontal, parietal, and insular regions, and increased working memory-related fMRI activation in frontal, cingulate, and visual association cortex. Controls showed only reductions in fusiform gyrus on VBM and FreeSurfer temporal and parietal cortex thickness. Women with breast cancer showed higher estimated brain age and lower regional gray matter volume than controls at both timepoints. The cancer group showed a trend toward decreased performance in attention, processing speed, and executive function over time. There were no significant associations between brain imaging metrics and cognition or days on hormonal therapy.ConclusionOlder women with breast cancer showed brain changes in the first year of hormonal therapy. Increased brain activation during working memory processing may be a sign of functional compensation for treatment-related structural changes. This hypothesis should be tested in larger samples over longer time periods.
Semantic speech networks linked to formal thought disorder in early psychosis
Authors: Nettekoven Caroline R , Diederen Kelly , Giles Oscar , Duncan Helen , Stenson Iain , Olah Julianna , Gibbs-Dean Toni , Collier Nigel , Vértes Petra E , Spencer Tom J , Morgan Sarah E , McGuire Philip 
Published: March 2022

Background and HypothesisMapping a patient’s speech as a network has proved to be a useful way of understanding formal thought disorder in psychosis. However, to date, graph theory tools have not incorporated the semantic content of speech, which is altered in psychosis.Study DesignWe developed an algorithm, “netts”, to map the semantic content of speech as a network, then applied netts to construct semantic speech networks for a general population sample, and a clinical sample comprising patients with first episode psychosis (FEP), people at clinical high risk of psychosis (CHR-P), and healthy controls.Study ResultsSemantic speech networks from the general population were more connected than size-matched randomised networks, with fewer and larger connected components, reflecting the non-random nature of speech. Networks from FEP patients were smaller than from healthy participants, for a picture description task but not a story recall task. For the former task, FEP networks were also more fragmented than those from controls; showing more, smaller connected components. CHR-P networks showed fragmentation values in-between FEP patients and controls. A clustering analysis suggested that semantic speech networks captured novel signal not already described by existing NLP measures. Network features were also related to negative symptom scores and scores on the Thought and Language Index, although these relationships did not survive correcting for multiple comparisons.ConclusionsOverall, these data suggest that semantic networks can enable deeper phenotyping of formal thought disorder in psychosis. We are releasing Netts as an open Python package alongside this manuscript.
LipidMS 3.0: an R-package and a web-based tool for LC-MS/MS data processing and lipid annotation
Authors: Alcoriza-Balaguer María Isabel , García-Cañaveras Juan Carlos , Ripoll-Esteve Francisco Javier , Roca Marta , Lahoz Agustín 
Published: March 2022

AbstractSummaryLipidMS was initially envisioned to use fragmentation rules and data-independent acquisition (DIA) for lipid annotation. However, data-dependent acquisition (DDA) remains the most widespread acquisition mode for untargeted LC-MS/MS-based lipidomics. Here we present LipidMS 3.0, an R package that not only adds DDA and new lipid classes to its pipeline, but also the required functionalities to cover the whole data analysis workflow from pre-processing (i.e., peak-peaking, alignment and grouping) to lipid annotation. We applied the new workflow in the data analysis of a commercial human serum pool spiked with 68 lipid standards acquired in the full scan, DDA and DIA modes. When focusing on the detected lipid standard features and total identified lipids, LipidMS 3.0 data pre-processing performance is similar to XCMS, whereas it complements the annotations provided by MS-DIAL, one of the most widely used tools in lipidomics. To extend and facilitate LipidMS 3.0 usage among less experienced R-programming users, the workflow was also implemented as a web-based application.Availability and ImplementationThe LipidMS R-package is freely available at https://CRAN.R-project.org/package=LipidMS and as a website at http://www.lipidms.com.Contactjuancarlos_garcia@iislafe.es, agustin.lahoz@uv.es
Human mesenchymal stem cells and derived extracellular vesicles reduce sensory neuron hyperexcitability and pain-related behaviors in a mouse model of osteoarthritis
Authors: Ai Minji , Hotham William E. , Pattison Luke A. , Ma Qingxi , Henson Frances M.D. , Smith Ewan St. John. 
Published: February 2022

AbstractOsteoarthritis (OA) is a common degenerative joint disease characterized by joint pain and stiffness. In humans, mesenchymal stem cells (MSCs) and derived extracellular vesicles (MSC-EVs) have been reported to alleviate pain in knee OA. Here, we used the destabilization of the medial meniscus (DMM) mouse model of OA to investigate mechanisms by which MSCs and MSC-EVs influence pain-related behavior. We found that MSC and MSC-EV treated DMM mice displayed improved OA pain-related behavior (i.e. locomotion, digging and sleep) compared to untreated DMM mice. Improved behavior was not the result of reduced joint damage, but rather knee-innervating sensory neurons from MSC and MSC-EV treated mice did not display the hyperexcitability observed in untreated DMM mice. Furthermore, we found that MSC-EVs normalize sensory neuron hyperexcitability induced by nerve growth factorin vitro. Our study suggests that MSCs and MSC-EVs may reduce pain in OA by direct action on peripheral sensory neurons.TeaserMesenchymal stem cells and secreted extracellular vesicles normalize sensory neuron excitability to reduce pain.
The GENOMES UNCOUPLED1 protein has an ancient, highly conserved role in chloroplast gene expression but not in retrograde signalling
Authors: Honkanen Suvi , Small Ian 
Published: February 2022

SummaryThe pentatricopeptide repeat protein GENOMES UNCOUPLED1 (GUN1) is required for chloroplast-to-nucleus signalling in response to plastid stress during chloroplast development in Arabidopsis thaliana but its exact molecular function remains unknown.We analysed GUN1 sequences in land plants and streptophyte algae. We tested functional conservation by complementation of the Arabidopsis gun1 mutant with GUN1 genes from the streptophyte alga Coleochate orbicularis or the liverwort Marchantia polymorpha. We also analysed the transcriptomes of M. polymorpha gun1 knock-out mutant lines during chloroplast development.GUN1 evolved within the streptophyte algal ancestors of land plants and is highly conserved among land plants but missing from the Rafflesiaceae that lack chloroplast genomes. GUN1 genes from C. orbicularis and M. polymorpha restore chloroplast retrograde signalling and suppress the cold-sensitive phenotype of the Arabidopsis gun1 mutant. However, GUN1 is not required for chloroplast retrograde signalling in the liverwort M. polymorpha.Our findings suggest that GUN1 is an ancient protein that evolved within the streptophyte algal ancestors of land plants before the first plants colonised land more than 470 million years ago. Its primary role is likely to be in chloroplast gene expression and its role in chloroplast retrograde signalling probably evolved more recently.
Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies
Authors: De Bastiani Marco Antônio , Bellaver Bruna , Brum Wagner S. , Souza Debora G. , Ferreira Pamela C. L. , Rocha Andreia S. , Povala Guilherme , Ferrari-Souza João Pedro , Benedet Andrea L. , Ashton Nicholas J. , Karikari Thomas K. , Zetterberg Henrik , Blennow Kaj , Rosa-Neto Pedro , Pascoal Tharick A. , Zimmer Eduardo R. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2022

AbstractIntroductionIn Alzheimer’s disease clinical research, glial fibrillary acidic protein (GFAP) released into the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis. However, it was demonstrated that GFAP levels differ in individuals presenting with amyloid-β (Aβ) or tau pathology. The molecular underpinnings behind this specificity are unexplored. Here we investigated biomarker and transcriptomic associations of GFAP-positive astrocytes with Aβ and tau pathologies in humans and mouse models.MethodsWe studied 90 individuals with plasma GFAP, Aβ- and Tau-PET to investigate the association between biomarkers. Then, transcriptomic analysis in hippocampal GFAP-positive astrocytes isolated from mouse models presenting Aβ (PS2APP) or tau (P301S) pathologies was applied to explore differentially expressed genes (DEGs), Gene Ontology processes, and protein-protein interaction networks associated with each phenotype.ResultsIn humans, we found that plasma GFAP associates with Aβ but not tau pathology. Unveiling the unique nature of GFAP-positive astrocytic responses to Aβ or tau pathology, mouse transcriptomics showed scarce overlap of DEGs between the Aβ and tau mouse models, While Aβ GFAP-positive astrocytes were overrepresented with genes associated with proteostasis and exocytosis-related processes, tau hippocampal GFAP-positive astrocytes presented greater abnormalities in functions related to DNA/RNA processing and cytoskeleton dynamics.ConclusionOur results offer insights into Aβ- and tau-driven specific signatures in GFAP-positive astrocytes. Characterizing how different underlying pathologies distinctly influence astrocyte responses is critical for the biological interpretation of astrocyte-related biomarker and suggests the need to develop context-specific astrocyte targets to study AD.FundingThis study was supported by Instituto Serrapilheira, Alzheimer’s Association, CAPES, CNPq and FAPERGS.