bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of COVID-19 Vaccines and Post-vaccination SARS-COV 2 Infection, Hospitalization, and Mortality: a Systematic Review and Meta-analysis of Observational Studies
Authors: Rahmani Kazem , Shavaleh Rasoul , Forouhi Mahtab , Disfani Hamideh Feiz , Kamandi Mostafa , Zadegan Dezfuli Aram Asareh , Oskooi Rozita Khatamian , Foogerdi Molood , Soltani Moslem 
Published: November 2021

AbstractIntroduction & ObjectiveVaccination is one of the most important and effective ways of preventing infectious diseases, and has recently been used in the COVID-19 epidemic and pandemic. The present meta-analysis study aimed to evaluate the effectiveness of COVID-19 vaccines in reducing the incidence of infection, hospitalization, and mortality in observational studies.Materials and MethodsA systematic search was performed independently in Scopus, PubMed, ProQuest, and Google Scholar electronic databases as well as Preprint servers using the keywords under study. The heterogeneity of the studies was assessed using I2and χ2 statistics, according to which the I2 of > 50% and P -value <0.1 was reported as heterogeneity of the studies. In addition, the Pooled Vaccine Effectiveness (PVE) obtained from the studies was calculated by converting (1-Pooled estimate × 100%) based on the type of outcome.ResultsA total of 54 records were included in this meta-analysis. The rate of PVE against SARS-COV 2 infection was about 71% (OR = 0.29, 95% CI: 0.23-0.36) in the first dose and 87% (OR = 0.13, 95% CI: 0.08-0.21) in the second, and the highest effectiveness in the first and second doses was that of BNT162b2 mRNA and combined studies. The PVE versus COVID-19-associated hospitalization was 73% (OR = 0.27, 95% CI: 0.18-0.41) in the first dose and 89% (OR = 0.11, 95% CI: 0.07-0.17) in the second. mRNA-1273 and combined studies in the first dose and ChAdOx1 and mRNA-1273 in the second dose had the highest effectiveness. Regarding the COVID-19-related mortality, PVE was about 28% (HR = 0.39, 95% CI: 0.23-0.45) in the first dose and 89% (HR = 0.11, 95% CI: 0.03-0.43) in the second.ConclusionThe evidence obtained from this study showed that the effectiveness of BNT162b2 mRNA, mRNA-1273, and ChAdOx1 in the first and second doses, and even combined studies were associated with increased effectiveness against SARS-COV2 infection, hospitalization, and death from COVID-19. In addition, considering that the second dose was significantly more efficient than the first one, a booster dose injection could be effective in high-risk individuals. On the other hand, it was important to observe other prevention considerations in the first days after taking the first dose.
Downsizing of contact tracing during COVID-19 vaccine roll-out
Authors: Martignoni Maria M. , Renault Josh , Baafi Joseph , Hurford Amy 
Published: November 2021

AbstractContact tracing is a key component of successful management of COVID-19. Contacts of infected individuals are asked to quarantine, which can significantly slow down (or prevent) community spread. Contact tracing is particularly effective when infections are detected quickly (e.g., through rapid testing), when contacts are traced with high probability, when the initial number of cases is low, and when social distancing and border restrictions are in place. However, the magnitude of the individual contribution of these factors in reducing epidemic spread and the impact of vaccination in determining contact tracing outputs is not fully understood. We present a delayed differential equation model to investigate how vaccine roll-out and the relaxation of social distancing requirements affect contact tracing practises. We provide an analytical criteria to determine the minimal contact tracing efficiency (defined as the the probability of identifying and quarantining contacts of symptomatic individuals) required to keep an outbreak under control, with respect to the contact rate and vaccination status of the population. Additionally, we consider how delays in outbreak detection and increased case importation rates affect the number of contacts to be traced daily. We show that in vaccinated communities a lower contact tracing efficiency is required to avoid uncontrolled epidemic spread, and delayed outbreak detection and relaxation of border restrictions do not lead to a significantly higher risk of overwhelming contact tracing. We find that investing in testing programs, rather than increasing the contact tracing capacity, has a larger impact in determining whether an outbreak will be controllable. This is because early detection activates contact tracing, which will slow, and eventually reverse exponential growth, while the contact tracing capacity is a threshold that will easily become overwhelmed if exponential growth is not curbed. Finally, we evaluate quarantine effectiveness during vaccine roll-out, by considering the proportion of people that will develop an infection while in isolation in relation to the vaccination status of the population and for different viral variants. We show that quarantine effectiveness decreases with increasing proportion of fully vaccinated individuals, and increases in the presence of more transmissible variants. These results suggest that a cost-effective approach during vaccine roll-out is to establish different quarantine rules for vaccinated and unvaccinated individuals, where rules should depend on viral trans-missibility. Altogether, our study provides quantitative information for contact tracing downsizing during vaccine roll-out, to guide COVID-19 exit strategies.
Recombination landscape dimorphism contributes to sex chromosome evolution in the dioecious plant Rumex hastatulus
Authors: Rifkin Joanna L. , Hnatovska Solomiya , Yuan Meng , Sacchi Bianca M. , Choudhury Baharul I. , Gong Yunchen , Rastas Pasi , Barrett Spencer C.H. , Wright Stephen I. 
Published: November 2021

SummaryThere is growing evidence across diverse taxa for sex differences in the genomic landscape of recombination, but the causes and consequences of these differences remain poorly understood. Strong recombination landscape dimorphism between the sexes could have important implications for the dynamics of sex chromosome evolution and turnover because low recombination in the heterogametic sex can help favour the spread of sexually antagonistic alleles. Here, we present a sex-specific linkage map and revised genome assembly of Rumex hastatulus, representing the first characterization of sex differences in recombination landscape in a dioecious plant. We provide evidence for strong sex differences in recombination, with pericentromeric regions of highly suppressed recombination in males that cover over half of the genome. These differences are found on autosomes as well as sex chromosomes, suggesting that pre-existing differences in recombination may have contributed to sex chromosome formation and divergence. Analysis of segregation distortion suggests that haploid selection due to pollen competition occurs disproportionately in regions with low male recombination. Our results are consistent with the hypothesis that sex differences in the recombination landscape contributed to the formation of a large heteromorphic pair of sex chromosomes, and that pollen competition is an important determinant of recombination dimorphism.
High-plex Multiomic Analysis in FFPE at Subcellular Level by Spatial Molecular Imaging
Authors: He Shanshan , Bhatt Ruchir , Brown Carl , Brown Emily A. , Buhr Derek L. , Chantranuvatana Kan , Danaher Patrick , Dunaway Dwayne , Garrison Ryan G. , Geiss Gary , Gregory Mark T. , Hoang Margaret L. , Khafizov Rustem , Killingbeck Emily E. , Kim Dae , Kim Tae Kyung , Kim Youngmi , Klock Andrew , Korukonda Mithra , Kutchma Alecksandr , Lewis Zachary R. , Liang Yan , Nelson Jeffrey S. , Ong Giang T. , Perillo Evan P. , Phan Joseph C. , Phan-Everson Tien , Piazza Erin , Rane Tushar , Reitz Zachary , Rhodes Michael , Rosenbloom Alyssa , Ross David , Sato Hiromi , Wardhani Aster W. , Williams-Wietzikoski Corey A. , Wu Lidan , Beechem Joseph M. 
Published: November 2021

AbstractThe Spatial Molecular Imaging platform (CosMxTM SMI, NanoString Technologies, Seattle, WA) utilizes high-plex in-situ imaging chemistry for both RNA and protein detection. This automated instrument provides 1000’s of plex, at high sensitivity (1 to 2 copies/cell), very low error rate (0.0092 false calls/cell) and background (∼0.04 counts/cell). The imaging system generates three-dimensional super-resolution localization of analytes at ∼2 million cells per sample, four samples per run. Cell segmentation is morphology-based using antibodies, compatible with FFPE samples. Multiomic data (980 RNAs, 108 proteins) were measured at subcellular resolution using FFPE tissues (non-small cell lung (NSCLC) and breast cancer) and allowed identification of over 18 distinct cell types, 10 unique tumor microenvironments, and 100 pairwise ligand-receptor interactions. Over 800,000 single cells and ∼260 million transcripts data are released into the public domain allowing extended data analysis by the entire spatial biology research community.
Trim41 is essential for preventing X chromosome chaotic synapsis in male mice
Authors: Oura Seiya , Hino Toshiaki , Satoh Takashi , Noda Taichi , Koyano Takayuki , Isotani Ayako , Matsuyama Makoto , Akira Shizuo , Ishiguro Kei-ichiro , Ikawa Masahito 
Published: November 2021

AbstractMeiosis is a hallmark event in germ cell development that accompanies sequential chromosome events executed by numerous molecules. Therefore, characterization of these factors is one of the best strategies to clarify the mechanism of meiosis. Here, we report tripartite motif-containing 41 (TRIM41), a ubiquitin ligase E3, as an essential factor for proper meiotic progression and fertility in male mice. Trim41 KO spermatocytes exhibited synaptonemal complex protein 3 (SYCP3) overloading, especially on the X chromosome, showing extensive self-synapsis of X chromosome and non-homologous synapsis between the X chromosome and autosomes. Furthermore, the mutant mice lacking the RING domain of TRIM41, required for the ubiquitin ligase E3 activity, phenocopied Trim41 KO mice. We then examined the behavior of mutant TRIM41 (ΔRING-TRIM41) and found that ΔRING-TRIM41 accumulated on the chromosome axes with overloaded SYCP3. This result showed that TRIM41 exerts the function on the chromosome axes. In summary, our study revealed that Trim41 is essential for preventing SYCP3 overloading and chaotic synapsis of the X chromosome, suggesting a TRIM41-mediated mechanism for regulating unsyapsed axes during male meiotic progression.Summary statementTrim41-disruption caused abnormal synapsis configuration of the X chromosome and complete infertility in male mice. Thus, TRIM41 prevents the sex chromosome from chaotic synapsis.
Restricting a single amino acid cross-protects D. melanogaster from nicotine poisoning through mTORC1 and GCN2 signalling
Authors: Fulton Tahlia L. , Mirth Christen K. , Piper Matthew D. W. 
Published: November 2021

AbstractDietary interventions that restrict protein intake have repeatedly been shown to offer beneficial health outcomes to the consumer. Benefits such as increased stress tolerance can be observed in response to restricting individual amino acids, thus mimicking dietary protein restriction. Here, we sought to further understand the relationship between dietary amino acids and stress tolerance using Drosophila melanogaster. Utilising a chemically defined medium for Drosophila, we found that transiently restricting adult flies of a single essential amino acid generally protects against a lethal dose of the naturally occurring insecticide, nicotine. This protection was conferred during the pre-treatment window, was specific for individual amino acids and depended on the identity of the focal amino acid, as well as the duration and intensity of its restriction. For instance, complete isoleucine deprivation for 7 days maximised its protective effect - increasing survival during nicotine exposure by 100%. However, a dose of 25% threonine was required to maximise its protective effect (53% enhanced survival). To understand the molecular basis of these effects, we modified the signalling of two cellular sensors of amino acids, GCN2 (General control non-derepressible) and mTORC1 (mechanistic Target of Rapamycin Complex 1) in combination with amino acid restriction. We found that GCN2 was necessary for diets to protect against nicotine, whereas suppression of mTORC1 was sufficient to induce nicotine resistance. This finding implies that amino acid restriction acts via amino acid signalling to cross-protect against seemingly unrelated stressors. Altogether, our study offers new insights into the physiological responses to restriction of individual amino acids that confer stress tolerance. This has broad potential for application in animal and human health.
Evolution during seed production for ecological restoration? A molecular analysis of 19 species finds only minor genomic changes
Authors: Conrady Malte , Lampei Christian , Bossdorf Oliver , Durka Walter , Bucharova Anna 
Published: November 2021

AbstractA growing number of restoration projects require large amounts of seeds. As harvesting natural populations cannot cover the demand, wild plants are often propagated in large-scale monocultures. There are concerns that this cultivation process may cause genetic drift and unintended selection, which would alter the genetic properties of the cultivated populations and reduce their genetic diversity. Such changes could reduce the pre-existing adaptation of restored populations, and limit their adaptability to environmental change.We used single nucleotide polymorphism (SNP) markers and a pool-sequencing approach to test for genetic differentiation and changes in gene diversity during cultivation in 19 wild grassland species, comparing the source populations and up to four consecutive cultivation generations grown from these sources. We then linked the magnitudes of genetic changes to the species’ breeding systems and seed dormancy, to understand the roles of these traits in genetic change.The propagation of native seeds for ecosystem restoration changed the genetic composition of the cultivated generations only moderately. The genetic differentiation we observed as a consequence of cultivation was much lower than the natural genetic differentiation between different source regions, and the propagated generations harbored even higher gene diversity than wild-collected seeds. Genetic change was stronger in self-compatible species, probably as a result of increased outcrossing in the monocultures.Synthesis and applicationsOur study indicates that large-scale seed production maintains the genetic integrity of natural populations. Increased genetic diversity may even increase the adaptive potential of propagated seeds, which makes them especially suitable for ecological restoration. However, we have been working with seeds from Germany and Austria, where the seed production is regulated and certified. Whether other seed production systems perform equally well remains to be tested.
Chemical inhibition of pathological reactive astrocytes promotes neural protection
Authors: Clayton Benjamin L.L. , Kristell James D. , Allan Kevin C. , Karl Molly , Garrison Eric , Maeno-Hikichi Yuka , Sturno Annalise M. , Shick H. Elizabeth , Miller Robert H. , Tesar Paul J. 
Published: November 2021

AbstractDisease, injury, and aging induce reactive astrocyte states with pathological functions1-4. In neurodegenerative diseases, inflammatory reactive astrocytes are abundant and contribute to progressive cell loss. Modulating the state or function of these reactive astrocytes thereby represents an attractive therapeutic goal5,6. Leveraging a cellular phenotypic screening platform, we show that chemical inhibitors of HDAC3 effectively block pathological astrocyte reactivity. Inhibition of HDAC3 reduces molecular and functional features of reactive astrocytes in vitro including inflammatory gene expression, cytokine secretion, and antigen presentation. Transcriptional and chromatin mapping studies show that HDAC3 inhibition mediates a switch between pro-inflammatory and anti-inflammatory states, which disarms the pathological functions of reactive astrocytes. Systemic administration of a blood-brain barrier penetrant chemical inhibitor of HDAC3, RGFP966, blocks reactive astrocyte formation and promotes axonal protection in vivo. Collectively, these results establish a platform for discovering chemical modulators of reactive astrocyte states, inform the mechanisms controlling astrocyte reactivity, and demonstrate the therapeutic potential of modulating astrocyte reactivity for neurodegenerative diseases.
Identification of candidate therapeutics and signaling pathways for multiple myeloma
Authors: Gu Hanming 
Published: November 2021

AbstractMultiple myeloma (MM), a plasma cell malignancy, is related to critical morbidity due to end-organ destruction. A number of factors affect the MM cell proliferation and functions. Though MM is not curable, novel targets and inhibitors have shown great effects on MM patients. Here, we aim to identify significant genes and signaling pathways of MM with SI2 treatment using a bioinformatics method. The GSE156871 dataset was originally produced by using the high-throughput BGISEQ-500. The KEGG and GO results suggested that biological pathways such as “the complement and coagulation cascades” and “the transcription activator activity” are mostly affected in the SI2 treatment of MM cells. Moreover, we identified several genes including SRC, KNG1, and PI3KCG were involved in the treatment of MM cells. Therefore, our study provides further insights into the treatment of MM.
The Role of Genetic Variation in Maize Response to Beneficial Endophytes
Authors: Schultz Corey , Brantley Kamaya , Wallace Jason 
Published: November 2021

AbstractBackgroundGrowth-promoting endophytes have great potential to boost crop production and sustainability. There is, however, a lack of research on how differences in the plant host affect an endophyte’s ability to promote growth. We set out to quantify how different maize genotypes respond to specific growth-promoting endophytes. We inoculated genetically diverse maize lines with three different known beneficial endophytes: Herbaspirillum seropedicae (a gram-negative bacteria), Burkholderia WP9 (a gram-negative bacteria), and Serendipita vermifera Subsp. bescii (a Basidiomycota fungus). Maize seedlings were grown for 3 weeks under controlled conditions in the greenhouse and assessed for various growth promotion phenotypes.ResultsWe found Herbaspirillum seropedicae to increase chlorophyll content, plant height, root length, and root volume significantly in different maize genotypes, while Burkholderia WP9 did not significantly promote growth in any lines under these conditions. Serendipita bescii significantly increased root and shoot mass for 4 maize genotypes, and growth promotion correlated with measured fungal abundance. Although plant genetic variation by itself had a strong effect on phenotype, its interaction with the different endophytes was weak, and the endophytes rarely produced consistent effects across different genotypes.ConclusionsThis genome-by-genome interaction indicates that the relationship between a plant host and beneficial endophytes is complex, and it may partly explain why many microbe-based growth stimulants fail to translate from laboratory settings to the field. Detangling these interactions will provide a ripe area for future studies to understand how to best harness beneficial endophytes for agriculture.
Sprod for De-noising Spatial Transcriptomics Data Based on Position and Image Information
Authors: Wang Yunguan , Song Bing , Wang Shidan , Chen Mingyi , Xie Yang , Xiao Guanghua , Wang Li , Wang Tao 
Published: November 2021

ABSTRACTSpatial transcriptomics (ST) technologies provide gene expression close to or even superior to single-cell resolution while retaining the physical locations of sequencing and often also providing matched pathology images. However, the expression data captured by ST technologies suffer from high noise levels, as a result of the shallow coverage in each sequencing unit. The extra experimental steps for preserving the spatial locations of sequencing could result in even more severe noises, compared to regular single-cell RNA-sequencing (scRNA-seq). Fortunately, such noises could be largely removed by leveraging information from the physical locations of sequencing, and the tissue and cellular organization reflected by corresponding pathology images. In this work, we demonstrated the extensive levels of noise in ST data. We developed a mathematical model, named Sprod, to impute accurate ST gene expression based on latent space and graph learning of matched location and imaging data. We comprehensively validated Sprod and demonstrated its advantages over prior methods for removing drop-outs in scRNA-seq data. We further showed that, after adequate imputation by Sprod, differential expression analyses, pseudotime analyses, and cell-to-cell interaction inferences yield significantly more informative results. Overall, we envision denoising by Sprod to become a key first step to empower ST technologies for biomedical discoveries and innovations.
Cas9-Assisted Biological Containment of a Genetically Engineered Human Commensal Bacterium and Genetic Elements
Authors: Hayashi Naoki , Lai Yong , Mimee Mark , Lu Timothy K. 
Published: November 2021

ABSTRACTSophisticated gene circuits built by synthetic biology can enable bacteria to sense their environment and respond predictably. Biosensing bacteria can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. To provide robust biocontainment for engineered bacteria, we devised a Cas9-assisted auxotrophic biocontainment system combining thymidine auxotrophy, an Engineered Riboregulator (ER) for controlled gene expression, and a CRISPR Device (CD). The CD prevents the engineered bacteria from acquiring thyA via horizontal gene transfer, which would disrupt the biocontainment system, and inhibits the spread of genetic elements by killing bacteria harboring the gene cassette. This system tunably controlled gene expression in the human gut commensal bacterium Bacteroides thetaiotaomicron, prevented escape from thymidine auxotrophy, and blocked transgene dissemination for at least 10 days. These capabilities were validated in vitro and in vivo. This biocontainment system exemplifies a powerful strategy for bringing genetically engineered microorganisms safely into biomedicine.