bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine Protection Against the SARS-CoV-2 Omicron Variant in Macaques
Authors: Chandrashekar Abishek , Yu Jingyou , McMahan Katherine , Jacob-Dolan Catherine , Liu Jinyan , He Xuan , Hope David , Anioke Tochi , Barrett Julia , Chung Benjamin , Hachmann Nicole P. , Lifton Michelle , Miller Jessica , Powers Olivia , Sciacca Michaela , Sellers Daniel , Siamatu Mazuba , Surve Nehalee , VanWyk Haley , Wan Huahua , Wu Cindy , Pessaint Laurent , Valentin Daniel , Van Ry Alex , Muench Jeanne , Boursiquot Mona , Cook Anthony , Velasco Jason , Teow Elyse , Boon Adrianus C.M. , Suthar Mehul S. , Jain Neharika , Martinot Amanda J. , Lewis Mark G. , Andersen Hanne , Barouch Dan H. 
Published: February 2022

ABSTRACTBackgroundThe rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. Immune correlates of vaccine protection against Omicron are not known.Methods30 cynomolgus macaques were immunized with homologous and heterologous prime-boost regimens with the mRNA-based BNT162b2 vaccine and the adenovirus vector-based Ad26.COV2.S vaccine. Following vaccination, animals were challenged with the SARS-CoV-2 Omicron variant by the intranasal and intratracheal routes.ResultsOmicron neutralizing antibodies were observed following the boost immunization and were higher in animals that received BNT162b2, whereas Omicron CD8+ T cell responses were higher in animals that received Ad26.COV2.S. Following Omicron challenge, sham controls showed more prolonged virus in nasal swabs than in bronchoalveolar lavage. Vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs, showing that current vaccines provide substantial protection against Omicron in this model. However, vaccinated animals that had moderate levels of Omicron neutralizing antibodies but negligible Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Virologic control correlated with both antibody and T cell responses.ConclusionsBNT162b2 and Ad26.COV2.S provided robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in macaques. Protection against this highly mutated SARS-CoV-2 variant correlated with both humoral and cellular immune responses.
Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity
Authors: Eckold Clare , van Doorn Cassandra L.R. , Ruslami Rovina , Ronacher Katharina , Riza Anca-Lelia , van Veen Suzanne , Lee Ji-Sook , Kumar Vinod , Kerry-Barnard Sarah , Malherbe Stephanus T. , Kleynhans Léanie , Stanley Kim , Joosten Simone A. , Critchley Julia A , Hill Philip C. , van Crevel Reinout , Wijmenga Cisca , Haks Mariëlle C. , Ioana Mihai , Alisjahbana Bachti , Walzl Gerhard , Ottenhoff Tom H. M. , Dockrell Hazel M. , Vianello Eleonora , Cliff Jacqueline M. 
Published: February 2022

AbstractBackgroundPeople with diabetes are more likely to develop tuberculosis (TB) and to have poor TB treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB-diabetes (TB-DM) co-morbidity have excessive inflammatory and reduced interferon responses at TB diagnosis. It is unknown whether this persists through treatment, potentially underlying adverse outcomes.MethodsPulmonary TB patients were recruited in South Africa, Indonesia and Romania, and classified as having TB-DM, TB with prediabetes, TB-related hyperglycaemia or uncomplicated TB, based on glycated haemoglobin (HbA1c) concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood samples collected at diagnosis and at regular intervals throughout treatment was measured by unbiased RNA-Seq and targeted Multiplex Ligation-dependent Probe Amplification.ResultsGene expression was modulated by TB treatment in all groups but to different extents, such that differences remained in people with TB-DM relative to TB-only throughout, including genes involved in innate responses, anti-microbial immunity and the inflammasome. People with prediabetes or with TB-related hyperglycaemia had gene expression more similar to people with TB-DM than TB-only throughout treatment. The overall pattern of change was similar across clinical groups irrespective of glycaemic index, permitting models predictive of TB treatment to be developed.ConclusionsThe exacerbated transcriptome changes seen in TB-DM take longer to resolve during TB treatment, indicating that prolonged treatment or host-directed therapy may be needed to improve TB treatment outcomes. Development of transcriptome-based biomarker signatures of TB-treatment response should include people with diabetes to be useful across populations.Key PointsHost blood transcriptomes are altered in tuberculosis, and further altered with diabetes co-morbidity. We have shown that there is similar resolution of transcriptomes through treatment, but with differing magnitude and kinetics in TB patients with or without diabetes.
Increased household transmission and immune escape of the SARS-CoV-2 Omicron variant compared to the Delta variant: evidence from Norwegian contact tracing and vaccination data
Authors: Jalali Neda , Brustad Hilde K. , Frigessi Arnoldo , MacDonald Emily , Meijerink Hinta , Feruglio Siri , Nygård Karin , Rø Gunnar Isaksson , Madslien Elisabeth H. , De Blasio Birgitte Freiesleben 
Published: February 2022

AbstractUnderstanding the rapid epidemic growth of the novel SARS-CoV-2 Omicron variant is critical for public health management. We compared the secondary attack rate (SAR) of the Omicron and Delta variants in households using Norwegian contact tracing data from December 2021 to January 2022. Omicron SAR was higher (51%) than Delta (36%), with a relative risk (RR) of 1.41 (95% CI 1.27-1.56). We observed increased susceptibility to Omicron infection in household contacts compared to Delta independent of vaccination status; however, considering booster vaccinated contacts, the mean SAR was lower for both variants. We found increased Omicron transmissibility in all vaccination groups of primary cases, except partially vaccinated, compared to Delta. In particular, Omicron SAR for boosted primary cases was high, 46% vs 11 % for Delta (RR 4.34; 95% CI 1.52-25.16). In conclusion, booster doses decrease the infection risk of Delta and Omicron but have limited effect in preventing Omicron transmission.
Identifying variation in GP referral rates: an observational study of outpatient headache referrals
Authors: Biggin Fran , Davies Quinta , Howcroft Timothy , Emsley Hedley , Knight Jo 
Published: February 2022

AbstractObjectiveTo identify GP surgeries with unexpected rates of referral to specialist services, using headache referrals to outpatient neurology as an example. Identifying surgeries with unexpectedly high or low referral rates allows for further investigation and potential support to be targeted where it is most likely to be effective.MethodsThis is a retrospective observational study using routinely collected and open-source data. Data was collected from a single consultant outpatient neurology clinic and 202 GP surgeries across seven CCGs in the Northwest of England. The number of headache referrals from each GP surgery during a study period of 3 ¼ years was used as the primary outcome in a poisson model. The standardised residuals from this model were then used to identify GP surgeries that were likely to have referred unexpected patient numbers for headaches to an outpatient neurology clinic during the study period.ResultsWe identified four GP surgeries with unexpected numbers of referrals. This model also showed that there were two main predictors of headache referral, namely other neurology referrals and the distance of the GP surgery from the outpatient clinic.ConclusionGP surgeries with unexpected numbers of referrals to specialist services were identified using a flexible methodology. This methodology was demonstrated using headache referrals but could be adapted to any type of referral or geographical area.
Factors associated with higher levels of grief and support needs among people bereaved during the pandemic: Results from a national online survey
Authors: Selman LE , Farnell D J J , Longo M , Goss S , Torrens-Burton A , Seddon K , Mayland C R , Machin L , Byrne A , Harrop E J 
Published: February 2022

AbstractBackgroundThe COVID-19 pandemic has affected millions of people’s experiences of bereavement. We aimed to identify risk factors for grief and support needs.MethodsOnline survey of people bereaved in the UK (deaths 16 March 2020-2 January 2021), recruited via media, social media, national associations/organisations. Grief was assessed using the Adult Attitude to Grief (AAG) scale, which calculates an overall index of vulnerability (IOV) (range 0-36). Practical and emotional support needs were assessed in 13 domains.Results711 participants, mean age 49.5 (SD 12.9, range 18-90). 628 (88.6%) were female. Mean age of the deceased 72.2 (SD 16.1). 311 (43.8%) deaths were from confirmed/suspected COVID-19. Mean IOV was 20.41 (95% CI = 20.06 to 20.77). 28.2% exhibited severe vulnerability (IOV ≥ 24). In six support domains relating to psycho-emotional support, 50% to 60% of respondents reported high/fairly high levels of need. Grief and support needs increased strongly for close relationships with the deceased (versus more distant) and with reported social isolation and loneliness (P < 0.001), whereas they reduced with age of the deceased above 40 to 50. Other risk factors were place of death and reduced support from health professionals after death (P < 0.05).ConclusionsHigh overall levels of vulnerability in grief and support needs were observed. Relationship with the deceased, age of the deceased, and social isolation and loneliness are potential indicators of those at risk of even higher vulnerability in grief and support needs. Healthcare professional support after death is associated with more positive bereavement outcomes.
Time to reinfection and vaccine breakthrough SARS-CoV-2 infections: a retrospective cohort study
Authors: Molani Sevda , Baumgartner Andrew M. , Hwang Yeon Mi , Duvvuri Venkata R. , Goldman Jason D. , Hadlock Jennifer J. 
Published: February 2022

AbstractBackgroundIt is important to understand how BNT162b2, mRNA-1273, and JNJ-78436735 COVID-19 vaccines, as well as prior infection, protect against breakthrough cases and reinfections. Real world evidence on acquired immunity from vaccines, and from SARS-CoV-2 infection, can help public health decision-makers understand disease dynamics and viral escape to inform resource allocation for curbing the spread of pandemic.MethodsThis retrospective cohort study presents demographic information, survival functions, and probability distributions for 2,627,914 patients who received recommended doses of COVID-19 vaccines, and 63,691 patients who had a prior COVID-19 infection. In addition, patients receiving different vaccines were matched by age, sex, ethnic group, state of residency, and the quarter of the year in 2021 the COVID-19 vaccine was completed, to support survival analysis on pairwise matched cohorts.FindingsEach of the three vaccines and infection-induced immunity all showed a high probability of survival against breakthrough or reinfection cases (mRNA-1273: 0.997, BNT162b2: 0.997, JNJ-78436735: 0.992, previous infection: 0.965 at 180 days). The incidence rate of reinfection among those unvaccinated and previously infected was higher than that of breakthrough among the vaccinated population (reinfection: 0.9%; breakthrough:0.4%). In addition, 280 vaccinated patients died (0.01% all-cause mortality) within 21 days of the last vaccine dose, and 5898 (3.1 %) died within 21 days of a positive COVID-19 test.ConclusionsDespite a gradual decline in vaccine-induced and infection-induced immunity, both acquired immunities were highly effective in preventing breakthrough and reinfection. In addition, for unvaccinated patients with COVID-19, those who did not die within 90 days of their initial infection (9565 deaths, 5.0% all-cause mortality rate), had a comparable asymptotic pattern of breakthrough infection as those who acquired immunity from a vaccine. Overall, the risks associated with COVID-19 infection are far greater than the marginal advantages of immunity acquired by prior infection.
Spatio-temporal monitoring of lake fish spawning activity using environmental DNA metabarcoding
Authors: Di Muri C. , Lawson Handley L. , Bean C. W. , Benucci M. , Harper L. R. , James B. , Li J. , Winfield I. J. , Hänfling B. 
Published: February 2022

AbstractDetermining the timing and location of fish reproductive events is crucial for the implementation of correct management and conservation schemes. Conventional methods used to monitor these events are often unable to assess the spawning activity directly or can be invasive and therefore problematic. This is especially the case when threatened fish populations are the study subject, such as the Arctic charr (Salvelinus alpinus L.) populations in Windermere (Cumbria, UK). Arctic charr populations have been studied in this lake since the 1940s, and the locations and characteristics of spawning grounds have been described in detail using techniques such as hydroacoustics, as well as physical and visual surveys of the lake bottom. Here, in conjunction with established netting surveys, we added an environmental DNA (eDNA) metabarcoding approach to assess the spatial distribution of Arctic charr in the lake throughout the year to test whether this tool could allow us to identify spawning locations and activity. Sampling was carried out between October 2017 and July 2018 at three locations in the lake, covering putative and known spawning sites. eDNA metabarcoding provided accurate spatial and temporal characterisation of Arctic charr spawning events. Peaks of Arctic charr read counts from eDNA metabarcoding were observed during the spawning season and at specific locations of both putative and known spawning sites. Net catches of mature Arctic charr individuals confirmed the association between the Arctic charr spawning activity and the peaks of eDNA metabarcoding read counts. This study demonstrates the ability of eDNA metabarcoding to effectively and efficiently characterize the spatial and temporal nature of fish spawning in lentic systems.
NGS data reveals the phyllosphere microbiome of wheat plants infected by the fungal pathogen Zymoseptoria tritici
Authors: Barroso-Bergada Didac , Massot Marie , Vignolles Noémie , d’Arcier Julie Faivre , Chancerel Emilie , Guichoux Erwan , Walker Anne-Sophie , Vacher Corinne , Bohan David A. , Laval Valérie , Suffert Frédéric 
Published: February 2022

AbstractThe fungal pathogen Zymoseptoria tritici is the causal agent of Septoria tritici blotch (STB), a major wheat disease in Western Europe. Microorganisms inhabiting wheat leaves might act as beneficial, biocontrol or facilitating agents that could limit or stimulate the development of Z. tritici. Improving our understanding of microbial communities in the wheat phyllosphere would lead to new insights into STB management. This resource announcement provides fungal and bacterial metabarcoding datasets obtained by sampling wheat leaves differing in the presence of symptoms caused by Z. tritici. Tissues were sampled from three wheat commercial varieties on three sampling dates during a cropping season. Weeds around wheat fields were sampled as well. In total, more than 450 leaf samples were collected. The pathogen Z. tritici was quantified using qPCR. We provide the raw metabarcoding datasets, the Amplicon Sequence Variant (ASV) tables obtained after bioinformatic processing, the metadata associated to each sample (sampling date, wheat variety and tissue health condition), a preliminary descriptive analysis of the data, and the code used for bioinformatic and descriptive statistical analysis.
Glycan shield of the ebolavirus envelope glycoprotein GP
Authors: Peng W. , Rayaprolu V. , Parvate A.D. , Pronker M.F. , Hui S. , Parekh D. , Shaffer K. , Yu X. , Saphire E.O. , Snijder J. 
Published: February 2022

AbstractThe envelope glycoprotein GP of the ebolaviruses is essential for host cell attachment and entry. It is also the primary target of the protective and neutralizing antibody response in both natural infection and vaccination. GP is heavily glycosylated with up to 17 predicted N-linked sites, numerous O-linked glycans in its disordered mucin-like domain (MLD), and three predicted C-linked mannosylation sites. Glycosylation of GP is important for host cell attachment to cell-surface lectins, as well as GP stability and fusion activity. Moreover, it has been shown to shield GP from neutralizing activity of serum antibodies. Here, we use mass spectrometry-based glycoproteomics to profile the site-specific glycosylation patterns of ebolavirus GP. We detect up to 16 unique O-linked glycosylation sites in the mucin-like domain, as well as two O-linked sites in the head and glycan cap domains of the receptor-binding GP1 subunit. Multiple O-linked glycans are observed at the S/T residues of N-linked glycosylation sequons, suggesting possible crosstalk between the two types of modifications. We also confirmed the presence of C-mannosylation at W288 in the context of trimeric GP. We find heterogenous, complex N-linked glycosylation at the majority of predicted sites as expected. By contrast, the two conserved sites N257 and N563 are enriched in unprocessed high-mannose and hybrid glycans, suggesting a role in host-cell attachment via DC-SIGN/L-SIGN. We discuss our findings in the context of antibody recognition to show how glycans contribute to and restrict neutralization epitopes. This information on how N-, O-, and C-linked glycans together build the heterogeneous glycan shield of GP can guide future immunological studies and functional interpretation of ebolavirus GP-antibody interactions.
Non-synaptic alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior
Authors: Malgady Jeffrey M. , Baez Alexander , Jimenez Kimberly , Hobel Zachary B. , Prager Eric M. , Zhang Qiangge , Feng Guoping , Plotkin Joshua L. 
Published: February 2022

SummaryDeletion of the OCD-associated gene SAP90/PSD-95-associated protein 3 (Sapap3), which encodes a postsynaptic anchoring protein at corticostriatal synapses, causes OCD-like motor behaviors in mice. While corticostriatal synaptic dysfunction is central to this phenotype, the striatum efficiently adapts to pathological changes, often in ways that expand upon the original circuit impairment. Here we show that SAPAP3 deletion causes non-synaptic and pathwayspecific alterations in dorsolateral striatum circuit function. While somatic excitability was elevated in striatal projection neurons (SPNs), dendritic excitability was exclusively enhanced in direct pathway SPNs. Layered on top of this, cholinergic modulation was altered in opposing ways: striatal cholinergic interneuron density and evoked acetylcholine release were elevated, while basal muscarinic modulation of SPNs was reduced. These data describe how SAPAP3 deletion alters the striatal landscape upon which impaired corticostriatal inputs will act, offering a basis for how pathological synaptic integration and unbalanced striatal output underlying OCD-like behaviors may be shaped.
Identification of functional Spo0A residues critical for sporulation in Clostridioides difficile
Authors: DiCandia Michael A. , Edwards Adrianne N. , Jones Joshua B. , Swaim Grace L. , Mills Brooke D. , McBride Shonna M. 
Published: February 2022

ABSTRACTClostridioides difficile is an anaerobic, Gram-positive pathogen that is responsible for C. difficile infection (CDI). To survive in the environment and spread to new hosts, C. difficile must form metabolically-dormant spores. The formation of spores requires activation of the transcription factor Spo0A, which is the master regulator of sporulation in all endospore-forming bacteria. Though the sporulation initiation pathway has been delineated in the Bacilli, including the model spore-former Bacillus subtilis, the direct regulators of Spo0A in C. difficile remain undefined. C. difficile Spo0A shares highly conserved protein interaction regions with the B. subtilis sporulation proteins Spo0F and Spo0A, although many of the interacting factors present in B. subtilis are not encoded in C. difficile. To determine if comparable Spo0A residues are important for C. difficile sporulation initiation, site-directed mutagenesis was performed at conserved receiver domain residues and the effects on sporulation were examined. Mutation of residues important for homodimerization and interaction with both positive and negative regulators of B. subtilis Spo0A and Spo0F impacted C. difficile Spo0A function. The data also demonstrated that mutation of many additional conserved residues altered C. difficile Spo0A activity, even when the corresponding Bacillus interacting proteins are not apparent in the C. difficile genome. Finally, the conserved aspartate residue at position 56 of C. difficile Spo0A was determined to be the phosphorylation site that is necessary for Spo0A activation. The finding that Spo0A interacting motifs maintain functionality suggests that C. difficile Spo0A interacts with yet unidentified proteins that regulate its activity and control spore formation.
High-throughput widefield fluorescence imaging of 3D samples using deep learning for 2D projection image restoration
Authors: Forsgren Edvin , Edlund Christoffer , Oliver Miniver , Barnes Kalpana , Sjögren Rickard , Jackson Timothy R. 
Published: February 2022

AbstractFluorescence microscopy has become a core tool for visualizing and quantifying the spatial and temporal dynamics of complex biological processes. Thanks to its low cost and ease-of-use, widefield fluorescent imaging remains one of the most widely used fluorescence microscopy imaging modalities. To accomplish imaging of 3D samples, conventional fluorescence imaging entails acquiring a sequence of 2D images spaced along the z-dimension, typically called a z-stack. Oftentimes, the next step is to project the 3D volume into a single 2D image, as 3D image data can be cumbersome to manage and challenging to analyze and interpret, effectively limiting the utlity of z-dimensional information. Furthermore, z-stack acquisition is often time-consuming and consequently may induce photodamage to the biological sample, which are both major hurdles for its application in experiments that require high-throughput, such as drug screening. As an alternative to z-stacks, axial sweep acquisition schemes have been proposed to circumvent these drawbacks and offers potential of 100-fold faster image acquisition for 3D-samples compared to z-stack acquisition but unfortunately results in blurry, low-quality raw 2D z-projected images. We propose a novel workflow to combine axial z-sweep acquisition with deep learning-based image restoration, ultimately enabling high-throughput and high-quality imaging of complex 3D-samples using 2D projection images. To demonstrate the capabilities of our proposed workflow, we apply it to live-cell imaging of 3D tumor spheroids and find we can produce high-fidelity images appropriate for quantitative analysis. Therefore, we conclude that combining axial z-sweep image acquisition with deep learning-based image restoration enables high-throughput and high-quality fluorescence imaging of complex 3D biological samples.