bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-adaptive Unsupervised Auditory Attention Decoding Using EEG-based Stimulus Reconstruction
Authors: Geirnaert Simon , Francart Tom , Bertrand Alexander 
Published: January 2022

AbstractThe goal of auditory attention decoding (AAD) is to determine to which speaker out of multiple competing speakers a listener is attending based on the brain signals recorded via, e.g., electroencephalography (EEG). AAD algorithms are a fundamental building block of so-called neuro-steered hearing devices that would allow identifying the speaker that should be amplified based on the brain activity. A common approach is to train a subject-specific stimulus decoder that reconstructs the amplitude envelope of the attended speech signal. However, training this decoder requires a dedicated ‘ground-truth’ EEG recording of the subject under test, during which the attended speaker is known. Furthermore, this decoder remains fixed during operation and can thus not adapt to changing conditions and situations. Therefore, we propose an online time-adaptive unsupervised stimulus reconstruction method that continuously and automatically adapts over time when new EEG and audio data are streaming in. The adaptive decoder does not require ground-truth attention labels obtained from a training session with the end-user and instead can be initialized with a generic subject-independent decoder or even completely random values. We propose two different implementations: a sliding window and recursive implementation, which we extensively validate on three independent datasets based on multiple performance metrics. We show that the proposed time-adaptive unsupervised decoder outperforms a time-invariant supervised decoder, representing an important step toward practically applicable AAD algorithms for neuro-steered hearing devices.
Analysis of historical selection in winter wheat
Authors: Yang Chin Jian , Ladejobi Olufunmilayo , Mott Richard , Powell Wayne , Mackay Ian 
Published: January 2022

AbstractWinter wheat is a major crop with a rich selection history in the modern era of crop breeding. Genetic gains across economically important traits like yield have been well characterized and are the major force driving its production. Winter wheat is also an excellent model for analyzing historical genetic selection. As a proof of concept, we analyze two major collections of winter wheat varieties that were bred in western Europe from 1916 to 2010, namely the Triticeae Genome (TG) and WAGTAIL panels, which include 333 and 403 varieties respectively. We develop and apply a selection mapping approach, Regression of Alleles on Years (RALLY), in these panels, as well as in simulated populations. RALLY maps loci under sustained historical selection by using a simple logistic model to regress allele counts on years of variety release. To control for drift-induced allele frequency change, we develop a hybrid approach of genomic control and delta control. Within the TG panel, we identify 22 significant RALLY quantitative selection loci (QSLs) and estimate the local heritabilities for 12 traits across these QSLs. By correlating predicted marker effects with RALLY regression estimates, we show that alleles whose frequencies have increased over time are heavily biased towards conferring positive yield effect, but negative effects in flowering time, lodging, plant height and grain protein content. Altogether, our results (1) demonstrate the use of RALLY to identify selected genomic regions while controlling for drift, and (2) reveal key patterns in the historical selection in winter wheat and guide its future breeding.Key MessageModelling of the distribution of allele frequency over year of variety release identifies major loci involved in historical breeding of winter wheat.
Orally administered antigen can reduce or exacerbate pathology in an animal model of inflammatory arthritis dependent upon the timing of administration
Authors: Meehan Gavin R , McInnes Iain B , Brewer James M , Garside Paul 
Published: January 2022

AbstractCurrently, treatments for rheumatoid arthritis (RA) are focussed on treatment of disease symptoms rather than addressing the cause of disease, which could lead to remission and cure. Central to disease development is the induction of autoimmunity through a breach of self-tolerance. There is considerable research in RA focussed on antigens and approaches to re-establish antigen specific tolerance. A crucial step in this research is to employ appropriate animal models to test prospective antigen specific immunotherapies, preferably in the context of joint inflammation.In this short communication, we use our previously developed model of antigen specific inflammatory arthritis in which OVA-specific TcR tg T cells drive breach of tolerance to endogenous antigens to determine the impact that the timing of therapy administration has upon disease progression. Using antigen feeding to induce tolerance we demonstrate that administration prior to articular challenge results in a reduced disease score as evidenced by pathology and serum antibody responses. By contrast, feeding antigen after articular challenge had the opposite effect and resulted in the exacerbation of pathology.Although preliminary, these data suggest that the timing of antigen administration may be key to the success of tolerogenic immunotherapies. This has important implications for the timing of potential tolerogenic therapies in patients.
Towards a unified model of naive T cell dynamics across the lifespan
Authors: Rane Sanket , Hogan Thea , Lee Edward S. , Seddon Benedict , Yates Andrew J. 
Published: January 2022

AbstractNaive CD4 and CD8 T cells are cornerstones of adaptive immunity, but the dynamics of their establishment early in life and how their kinetics change as they mature following release from the thymus are poorly understood. Further, due to the diverse signals implicated in naive T cell survival, it has been a long-held and conceptually attractive view that they are sustained by active homeostatic control as thymic activity wanes. Here we employ multiple experimental systems to identify a unified model of naive CD4 and CD8 T cell population dynamics across the mouse lifespan. We infer that both subsets divide rarely and progressively increase their survival capacity with cell age. Strikingly, this simple model captures naive CD4 T cell dynamics throughout life. In contrast, we find that newly generated naive CD8 T cells are lost more rapidly during the first 3–4 weeks of life, likely due to increased recruitment into memory. We find no evidence for elevated division rates in neonates, or for feedback regulation of naive T cell numbers at any age. We show how confronting mathematical models with diverse datasets can reveal a quantitative and remarkably simple picture of naive T cell dynamics from birth into old age.
Interspecies transfer of syntenic RAMOSA1 orthologs and promoter cis sequences impacts maize inflorescence architecture
Authors: Strable Josh , Unger-Wallace Erica , Raygoza Alejandro Aragón , Briggs Sarah , Vollbrecht Erik 
Published: January 2022

ABSTRACTGrass inflorescences support floral structures that each bear a single grain, where variation in branch architecture directly impacts yield. The maize RAMOSA1 (ZmRA1) transcription factor acts as a key regulator of inflorescence development by imposing branch meristem determinacy. Here, we show RA1 transcripts accumulate in boundary domains adjacent to spikelet meristems in Sorghum bicolor (Sb) and Setaria viridis (Sv) inflorescences similar as in the developing maize tassel and ear. To evaluate functional conservation of syntenic RA1 orthologs and promoter cis sequences in maize, sorghum and setaria, we utilized interspecies gene transfer and assayed genetic complementation in a common inbred background by quantifying recovery of normal branching in highly ramified ra1-R mutants. A ZmRA1 transgene that includes endogenous upstream and downstream flanking sequences recovered normal tassel and ear branching in ra1-R. Interspecies expression of two transgene variants of the SbRA1 locus, modeled as the entire endogenous tandem duplication or just the non-frameshifted downstream copy, complemented ra1-R branching defects and induced novel fasciation and branch patterns. The SvRA1 locus lacks conserved, upstream noncoding cis sequences found in maize and sorghum; interspecies expression of an SvRA1 transgene did not or only partially recovered normal inflorescence forms. Driving expression of the SvRA1 coding region by the ZmRA1 upstream region, however, recovered normal inflorescence morphology in ra1-R. These data leveraging interspecies gene transfer suggest that cis-encoded temporal regulation of RA1 expression is a key factor in modulating branch meristem determinacy that ultimately impacts grass inflorescence architecture.
Compartmentalized Cell Envelope Biosynthesis in Mycobacterium tuberculosis
Authors: Puffal Julia , Sparks Ian L. , Brenner James R. , Li Xuni , Leszyk John D. , Hayashi Jennifer M. , Shaffer Scott A. , Morita Yasu S. 
Published: January 2022

AbstractThe intracellular membrane domain (IMD) is a metabolically active and laterally discrete membrane domain initially discovered in Mycobacterium smegmatis. The IMD correlates both temporally and spatially with the polar cell envelope elongation in M. smegmatis. Whether or not a similar membrane domain exists in pathogenic species remains unknown. Here we show that the IMD is a conserved membrane structure found in Mycobacterium tuberculosis. We used two independent approaches, density gradient fractionation of membrane domains and visualization of IMD-associated proteins through fluorescence microscopy, to determine the characteristics of the plasma membrane compartmentalization in M. tuberculosis. Proteomic analysis revealed that the IMD is enriched in metabolic enzymes that are involved in the synthesis of conserved cell envelope components such as peptidoglycan, arabinogalactan, and phosphatidylinositol mannosides. Using a fluorescent protein fusion of IMD-associated proteins, we demonstrated that this domain is concentrated in the polar region of the rod-shaped cells, where active cell envelope biosynthesis is taking place. Proteomic analysis further revealed the enrichment of enzymes involved in synthesis of phthiocerol dimycocerosates and phenolic glycolipids in the IMD. We validated the IMD association of two enzymes, α1,3-fucosyltransferase and fucosyl 4- O-methyltransferase, which are involved in the final maturation steps of phenolic glycolipid biosynthesis. Taken together, these data indicate that functional compartmentalization of membrane is an evolutionarily conserved feature found in both M. tuberculosis and M. smegmatis, and M. tuberculosis utilizes this membrane location for the synthesis of its surface- exposed lipid virulence factors.IMPORTANCEM. tuberculosis remains an important public health threat, with more than one million deaths every year. The pathogen’s ability to survive in the human host for decades highlights the importance of understanding how this bacterium regulates and coordinates its metabolism, cell envelope elongation, and growth. The IMD is a membrane structure that associates with the subpolar growth zone of actively growing mycobacteria, but its existence is only known in a non- pathogenic model, M. smegmatis. Here, we demonstrated the presence of the IMD in M. tuberculosis, making the IMD an evolutionarily conserved plasma membrane compartment in mycobacteria. Furthermore, our study revealed that the IMD is the factory for synthesizing phenolic glycolipids, virulence factors produced by slow-growing pathogenic species.
SARS-CoV-2-positive patients display considerable differences in proteome diversity in urine, nasopharyngeal, gargle solution and bronchoalveolar lavage fluid samples
Authors: Okendo Javan , Musanabaganwa Clarisse , Mwangi Peter , Nyaga Martin , Onywera Harris 
Published: January 2022

AbstractBackgroundProteome profile changes post-severe acute respiratory syndrome coronavirus 2 (post-SARS-CoV-2) infection in different body sites of humans remains an active scientific investigation whose solutions stand a chance of providing more information on what constitutes SARS-CoV-2 pathogenesis. While proteomics has been used to understand SARS-CoV-2 pathogenesis, there are limited data about the status of proteome profile in different human body sites infected by the sarscov2 virus. To bridge the gap, our study aims to profile the proteins secreted in urine, bronchoalveolar lavage fluid (BALF), gargle solution, and nasopharyngeal samples and assess the proteome differences in these body samples collected from SARS-CoV-2-positive patients.Materials and methodsWe downloaded publicly available proteomic data from (https://www.ebi.ac.uk/pride/). The data we downloaded had the following identifiers: i) PXD019423, n=3 from Charles Tanford Protein Center in Germany. ii) PXD018970, n=15 from Beijing Proteome Research Centre, China. iii)PXD022085, n=5 from Huazhong University of Science and Technology, China, and iv) PXD022889, n=18 from Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905 USA. MaxQuant was used for the peptide spectral matching using humans, and SARS-CoV-2 was downloaded from the UniProt database (access date 13th October 2021).ResultsThe individuals infected with SARS-CoV-2 viruses displayed a different proteome diversity from the different body sites we investigated. Overall, we identified 1809 proteins across the four different sample types we compared. Urine and BALF samples had significantly more abundant SARS-CoV-2 proteins than the other body sites we compared. Urine samples had 257(33.7%) unique proteins, followed by nasopharyngeal with 250(32.8%) unique proteins. Garage solution and BALF had 38(5%) and 73(9.6%) unique proteins.ConclusionsUrine, gargle solution, nasopharyngeal, and bronchoalveolar lavage fluid samples have different protein diversity in individuals infected with SARS-CoV-2. Moreover, our data demonstrated that a given body site is characterized by a unique set of proteins in SARS-CoV-2 seropositive individuals.
A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron
Authors: Lai Eric , Becker David , Brzoska Pius , Cassens Tyler , Davis-Turak Jeremy , Diamond Evan , Furtado Manohar , Gandhi Manoj , Gort Dale , Greninger Alexander L. , Hajian Pooneh , Hayashibara Kathleen , Kennedy Emily B. , Laurent Marc , Lee William , Leonetti Nicole A. , Lozach Jean , Lu James , Nguyen Jason M. , O’Donovan K. M. Clair , Peck Troy , Radcliffe Gail E. , Ramirez Jimmy M. , Roychoudhury Pavitra , Sandoval Efren , Walsh Brian , Weinell Marianne , Wesselman Cassandra , Wesselman Timothy , White Simon , Williams Stephen , Wong David , Yu Yufei , Creager Richard S. 
Published: January 2022

AbstractThe rapid emergence of new SARS-CoV-2 variants raises a number of public health questions including the capability of diagnostic tests to detect new strains, the efficacy of vaccines, and how to map the geographical distribution of variants to better understand patterns of transmission and possible load on healthcare resources. Next-Generation Sequencing (NGS) is the primary method for detecting and tracing the emergence of new variants, but it is expensive, and it can take weeks before sequence data is available in public repositories. Here, we describe a Polymerase Chain Reaction (PCR)-based genotyping approach that is significantly less expensive, accelerates reporting on SARS-CoV-2 variants, and can be implemented in any testing lab performing PCR.Specific Single Nucleotide Polymorphisms (SNPs) and indels are identified that have high positive percent agreement (PPA) and negative percent agreement (NPA) compared to NGS for the major genotypes that circulated in 2021. Using a 48-marker panel, testing on 1,128 retrospective samples yielded a PPA and NPA in the 96.3 to 100% and 99.2 to 100% range, respectively, for the top 10 most prevalent lineages. The effect on PPA and NPA of reducing the number of panel markers was also explored.In addition, with the emergence of Omicron, we also developed an Omicron genotyping panel that distinguishes the Delta and Omicron variants using four (4) highly specific SNPs. Data from testing demonstrates the capability to use the panel to rapidly track the growing prevalence of the Omicron variant in the United States in December 2021.
Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures
Authors: Taeschler Patrick , Cervia Carlo , Zurbuchen Yves , Hasler Sara , Pou Christian , Tan Ziyang , Adamo Sarah , Raeber Miro E. , Bächli Esther , Rudiger Alain , Stüssi-Helbling Melina , Huber Lars C. , Brodin Petter , Nilsson Jakob , Probst-Müller Elsbeth , Boyman Onur 
Published: January 2022

AbstractBackgroundSeveral autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19.MethodsWe performed highly sensitive indirect immunofluorescence assays to detect anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed-up to one year after infection, eleven vaccinated individuals, and 41 unexposed controls.ResultsCompared to healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA- negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B cell compartment after recovery.ConclusionHighly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased anti-viral humoral immune responses and inflammatory immune signatures.
Estimation of the test to test distribution as a proxy for generation interval distribution for the Omicron variant in England
Authors: Abbott Sam , Sherratt Katharine , Gerstung Moritz , Funk Sebastian 
Published: January 2022

AbstractBackgroundEarly estimates from South Africa indicated that the Omicron COVID-19 variant may be both more transmissible and have greater immune escape than the previously dominant Delta variant. The rapid turnover of the latest epidemic wave in South Africa as well as initial evidence from contact tracing and household infection studies has prompted speculation that the generation time of the Omicron variant may be shorter in comparable settings than the generation time of the Delta variant.MethodsWe estimated daily growth rates for the Omicron and Delta variants in each UKHSA region from the 23rd of November to the 23rd of December 2021 using surveillance case counts by date of specimen and S-gene target failure status with an autoregressive model that allowed for time-varying differences in the transmission advantage of the Delta variant where the evidence supported this. By assuming a gamma distributed generation distribution we then estimated the generation time distribution and transmission advantage of the Omicron variant that would be required to explain this time varying advantage. We repeated this estimation process using two different prior estimates for the generation time of the Delta variant first based on household transmission and then based on its intrinsic generation time.ResultsVisualising our growth rate estimates provided initial evidence for a difference in generation time distributions. Assuming a generation time distribution for Delta with a mean of 2.5-4 days (90% credible interval) and a standard deviation of 1.9-3 days we estimated a shorter generation time distribution for Omicron with a mean of 1.5-3.2 days and a standard deviation of 1.3-4.6 days. This implied a transmission advantage for Omicron in this setting of 160%-210% compared to Delta. We found similar relative results using an estimate of the intrinsic generation time for Delta though all estimates increased in magnitude due to the longer assumed generation time.ConclusionsWe found that a reduction in the generation time of Omicron compared to Delta was able to explain the observed variation over time in the transmission advantage of the Omicron variant. However, this analysis cannot rule out the role of other factors such as differences in the populations the variants were mixing in, differences in immune escape between variants or bias due to using the test to test distribution as a proxy for the generation time distribution.
The skin we live in: pigmentation traits and tanning behaviour in British young adults, an observational and genetically-informed study
Authors: Bonilla Carolina , Mejia-Lancheros Cilia 
Published: January 2022

AbstractBackgroundSkin cancer incidence has been increasing worldwide, representing a particularly high burden for populations of European ancestry. Outdoor and indoor tanning using ultraviolet radiation (UVR) devices are major risk factors for skin cancer. While tanning behaviours can be modified by targeted interventions to reduce skin cancer rates, there is insufficient evidence on the motivations for tanning preferences and their relationship with pigmentation phenotypes. The present observational and genetically- informed study investigates motives for tanning and the role that pigmentation phenotypes play on outdoor and indoor tanning behaviour in British young adults.MethodsThis study included 3722 participants from the Avon Longitudinal Study of Parents and Children in South West England. Skin, hair and eye colour features, and tanning ability and preferences were collected using a questionnaire applied when participants were ∼25 years of age. Genotypes for 41 single nucleotide polymorphisms (SNPs) associated with pigmentation were obtained from a subset of participants who provided a biological sample, and used to estimate the probability of having particular pigmentation traits with the HIrisPlex-S system.ResultsLiking to tan and outdoor tanning were strongly influenced by skin, hair and eye pigmentation, and tanning ability. However, the association of these traits with UV indoor tanning was weaker. Conversely, females, participants of lower socioeconomic position, individuals who were unhappy with their pigmentation phenotype during adolescence, and participants who believed that tanning helps prevent sunburn were more likely to have used UVR-based tanning devices.ConclusionOur results provide evidence to support the implementation of skin cancer preventative interventions that consider individual biological characteristics and motives for undergoing outdoor and indoor tanning.