bluuebunny/crossref_metadata_2025_split huggingface dataset:
md_harmonize: a Python package for atom-level harmonization of public metabolic databases
Authors: Jin Huan , Moseley Hunter N.B. 
Published: December 2022

AbstractSummaryA big challenge to integrating public metabolic resources is the use of different nomenclatures by individual databases. This paper presents md_harmonize, an open-source Python package for harmonizing compounds and metabolic reactions across various metabolic databases. md_harmonize utilizes a neighborhood-specific graph coloring method for generating a unique identifier for each compound via atom identifiers based on the compound structure. The resulting harmonized compounds and reactions can be used to construct metabolic networks and models for various downstream analyses, including metabolic flux analysis.AvailabilityThe md_harmonize package is implemented in Python and freely available athttps://github.com/MoseleyBioinformaticsLab/md_harmonizeContacthunter.moseley@uky.eduSupplementary informationSupplementary data are available athttps://doi.org/10.6084/m9.figshare.21699683.
The effect of vaccination on transmission of SARS-CoV-2 (COVID-19): a rapid review
Authors: Williams Jessica , Barratte Sasha , Winfield Tom , Elston Lauren , McDermott Katie , Jarrom David , Hasler Elise , Potter Caron , Lewis Ruth , Cooper Alison , Edwards Adrian 
Published: December 2022

AbstractThis is an update (literature search up to 15 March 2022) of arapid reviewexamining whether vaccination against SARS-CoV-2 (COVID-19) affects transmission of SARS-CoV-2.Streamlined systematic methodologies were used to accelerate the review process.The update identified 17 additional studies: 6 studies reported on transmission and 11 studies reported viral load. There was high heterogeneity across studies, which varied in design, participant characteristics and SARS-CoV-2 variants reported. Evidence from this update supports previous findings that that transmission of Omicron and Delta variants is lowest in booster-vaccinated people, followed by fully vaccinated people, with the highest rate of transmission in unvaccinated people. Additionally, some studies compared transmission between different variants or sub-variants; risk of transmission appears to be higher with Omicron than Delta, regardless of vaccination status.Funding statementHealth Technology Wales was funded for this work by the Wales COVID-19 Evidence Centre, itself funded by Health and Care Research Wales on behalf of Welsh Government.
Cuticle supplementation and nitrogen recycling by a dual bacterial symbiosis in a family of xylophagous beetles (Coleoptera: Bostrichidae)
Authors: Kiefer Julian Simon Thilo , Bauer Eugen , Okude Genta , Fukatsu Takema , Kaltenpoth Martin , Engl Tobias 
Published: December 2022

AbstractMany insects engage in stable nutritional symbioses with bacteria that supplement limiting essential nutrients to their host. While several plant sap-feeding Hemipteran lineages are known to be simultaneously associated with two or more endosymbionts with complementary biosynthetic pathways to synthesize amino acids or vitamins, such co-obligate symbioses have not been functionally characterized in other insect orders. Here, we report on the characterization of a dual co-obligate, bacteriome-localized symbiosis in a family of xylophagous beetles using comparative genomics, fluorescence microscopy, and phylogenetic analyses. Across the beetle family Bostrichidae, all investigated species harbored the Bacteroidota symbiontShikimatogenerans bostrichidophilusthat encodes the shikimate pathway to produce tyrosine precursors in its severely reduced genome, likely supplementing the beetles’ cuticle biosynthesis, sclerotisation, and melanisation. One clade of Bostrichid beetles additionally housed the co-obligate symbiontBostrichicola ureolyticusthat is inferred to complement the function ofShikimatogeneransby recycling urea and provisioning the essential amino acid lysine, thereby providing additional benefits on nitrogen-poor diets. Both symbionts represent ancient associations within the Bostrichidae that have subsequently experienced genome erosion and co-speciation with their hosts. WhileBostrichicolawas repeatedly lost,Shikimatogeneranshas been retained throughout the family and exhibits a perfect pattern of co-speciation. Our results reveal that co-obligate symbioses with complementary metabolic capabilities occur beyond the well-known sap-feeding Hemiptera and highlight the importance of symbiont-mediated cuticle supplementation and nitrogen recycling for herbivorous beetles.Significance statementNutritional symbioses evolved frequently in insects and contribute diverse metabolites to their hosts’ physiology. Associations with dual symbionts providing complementary nutrients evolved in multiple Hemiptera lineages, compensating eroded biosynthetic capabilities of primary symbionts. Bostrichidae, a family of xylophagous beetles, harbor consistently a Flavobacterial symbiont encoding exclusively the Shikimate pathway to synthesis precursors of tyrosine. However, in two families a second, closely Flavobacterial symbiont capable of recycling urea and synthesizing lysine was retained. Both symbionts exhibit high genomic syntheny and tight co-cladogenesis with the host phylogeny, indicating ancestral, ecological highly beneficial symbioses.
The Arabidopsis Target of Rapamycin (TOR) kinase regulates ammonium assimilation and glutamine metabolism
Authors: Ingargiola Camille , Jéhanno Isabelle , Forzani Céline , Marmagne Anne , Broutin Justine , Clément Gilles , Leprince Anne-Sophie , Meyer Christian 
Published: December 2022

AbstractIn Eukaryotes, Target of Rapamycin (TOR) is a well conserved kinase that controls cell metabolism and growth in response to nutrients and environmental factors. Nitrogen (N) is an essential element for plants and TOR functions as a crucial N and amino acid sensor in animals and yeast. However, the knowledge on the connections between TOR and the overall N metabolism and assimilation in plants is still limited. In this study, we investigate the regulation of TOR in Arabidopsis by the N source as well as the impact of TOR deficiency on N metabolism. Inhibition of TOR globally decreases ammonium uptake while triggering a massive accumulation of amino acids such as Gln, but also of polyamines. Coherently, TOR complex mutants were found to be hypersensitive to Gln. We also show that the glutamine synthetase inhibitor glufosinate abolishes Gln accumulation resulting from TOR inhibition and improves the growth of TOR complex mutants. These results suggest that a high level of Gln contributes to the reduction in plant growth resulting from TOR inhibition. Glutamine synthetase activity was reduced by TOR inhibition while the enzyme amount increased. In conclusion our findings show that the TOR pathway is intimately connected to N metabolism and that a decrease in TOR activity results in a glutamine synthetase-dependent Gln and amino acids accumulation.One sentence summaryThe conserved Target of Rapamycin (TOR) kinase is an important sensor and regulator of the nitrogen metabolism and here we show that inhibiting this kinase affects ammonium uptake and results in Gln accumulation in a glutamine synthetase-dependent manner.
Cuticle development and underlying transcriptome-metabolome associations during early seedling establishment
Authors: Chen Keting , Bhunia Rupam Kumar , McNinch Colton , Campidilli Grace , Hassan Ahmed , Li Ling , Nikolau Basil J. , Yandeau-Nelson Marna D. 
Published: December 2022

ABSTRACTThe plant cuticle is a complex extracellular lipid barrier that provides protection from numerous environmental stressors and is critical for normal organ development. In this study, we investigated cuticle deposition by integrating metabolomics and transcriptomics data gathered from six different maize seedling organs of four genotypes, the inbred lines B73 and Mo17, and their reciprocal hybrids. These datasets captured the developmental transition of the seedling from heterotrophic skotomorphogenic growth to autotrophic photomorphogenic growth, which is a transition that is highly vulnerable to environmental stresses. Statistical interrogation of these data reveals that the predominant determinant of cuticle composition is seedling organ type, whereas the seedling genotype has a smaller effect on this phenotype. Gene-to-metabolite associations assessed by joint statistical analyses of transcriptome and metabolome datasets identified three gene networks connected with the deposition of different fractions of the cuticle: a) cuticular waxes; b) cutin of aerial organs and suberin of roots; and c) both of these fractions. These networks consist of genes that encode known components of the machinery that supports cuticle deposition, demonstrating the utility of this integrated omics approach. Moreover, these gene networks reveal three additional metabolic programs that appear to support cuticle deposition, including processes of a) chloroplast biogenesis, b) lipid metabolism, and c) molecular regulation (e.g., transcription factors, post-translational regulators and phytohormones). This study demonstrates the wider physiological metabolic context that can determine cuticle deposition and lays the groundwork for new targets for modulating properties of this protective barrier.
The Use and Safety Risk of Repurposed Drugs for COVID-19 patients: Lessons Learned Utilizing the Food and Drug Administration’s Adverse Event Reporting System
Authors: Alsuhaibani Deemah S. , Edrees Heba H. , Alshammari Thamir M 
Published: December 2022

AbstractObjectivesThis study was designed to assess the disproportionality analyses of adverse drug reactions (ADRs) related to hydroxychloroquine and remdesivir and how ADR reporting fluctuated during the COVID-19 pandemic.MethodsA retrospective observational study was conducted utilizing the Food and Drug Administration’s Adverse Event Reporting System (FAERS) data between 2019 and 2021. The study was conducted in two phases. In the first phase, all reports associated with the drugs of interest were evaluated to assess all related adverse drug reactions. In the second phase, specific outcomes of interest (i.e., QT prolongation and renal and hepatic events) were determined to study their association with the drugs of interest. A descriptive analysis was conducted for all adverse reactions related to the drugs being studied. In addition, disproportionality analyses were conducted to compute the reporting odds ratio, the proportional reporting ratio, the information component, and the empirical Bayes geometric mean. All analyses were conducted using RStudio.ResultsA total of 9,443 ADR reports related to hydroxychloroquine; 6,160 (71.49) patients were female, and higher percentage of patients of both sexes were over the age of 65 years. QT prolongation (1.48%), pain (1.38%), and arthralgia (1.25%) were most frequently reported ADRs during the COVID-19 pandemic. The association of QT prolongation with use of hydroxychloroquine was statistically significant (ROR 47.28 [95% CI 35.95-62.18]; PRR 42.41 [95% CI 32.25-55.78]; EBGM 16.08; IC 4.95) compared with fluoroquinolone. The outcome was serious medical events in 48.01% of ADR reports; 27.42% required hospitalization and 8.61% resulted in death. Of 6,673 ADR reports related to remdesivir, 3,928 (61.13%) patients were male. During 2020, the top three ADR reports were elevated liver function tests (17.26%), acute kidney injury (5.95%) and death (2.84%). Additionally, 42.71% of ADR reports indicated serious medical events; 19.69% resulted in death and 11.71% indicated hospitalization. The ROR and PRR of hepatic and renal events associated with remdesivir were statistically significant, (4.81 [95% CI 4.46-5.19] and 2.96 [95% CI 2.66-3.29], respectively.ConclusionOur study showed that several serious ADRs were reported with the use of hydroxychloroquine, which resulted in hospitalization and death. Trends with the use of remdesivir were similar, but to a lesser extent. Therefore, this study showed us that off-label use should be based on thorough evidence-based evaluation.
Identification of Barley Enhancers across Genome via STARR-seq
Authors: Zhou Wanlin , Shi Haoran , Wang Zhiqiang , Huang Yuxin , Ni Lin , Chen Xudong , Liu Yan , Li Haojie , Li Caixia , Liu Yaxi 
Published: December 2022

AbstractEnhancers are DNA sequences that can strengthen transcription initiation. However, the global identification of plant enhancers is complicated due to uncertainty in the distance and orientation of enhancers, especially in species with large genomes. In this study, we performed self-transcribing active regulatory region sequencing (STARR-seq) for the first time to identify enhancers across the barley genome. A total of 7323 enhancers were successfully identified, and among 45 randomly selected enhancers, over 75% were effective as validated by a dual-luciferase reporter assay system in the lower epidermis of tobacco leaves. Interestingly, up to 53.5% of the barley enhancers were repetitive sequences, especially transposable elements (TEs), thus reinforcing the vital role of repetitive enhancers in gene expression. Both the common active transcription marker H3K4me3 and repressive histone marker H3K27me3 were abundant among the barley STARR-seq enhancers. In addition, the functional range of barley STARR-seq enhancers seemed much broader than that of rice or maize and extended to ± 100 KB of the gene body, and this finding was consistent with the high expression levels of genes in the genome. This work specifically depicts the unique features of barley enhancers and provides available barley enhancers for further utilization.
Different neuroendocrine cell types in thepars intercerebralisofPeriplaneta americanaproduce their own specific IGF-related peptides
Authors: Veenstra Jan A. 
Published: December 2022

AbstractOf the nine genes of the American cockroach,Periplaneta americana, coding for peptides related to insulin and insulin-like growth factor, seven show significant expression in the central nervous system as demonstrated by the polymerase chain reaction on reverse transcribed RNA.In situhybridisation shows that five of those are expressed by cells in thepars intercerebralis. Antisera raised to the predicted peptides show that these cells are neuroendocrine in nature and project to thecorpora cardiaca. Interestingly, there are at least three cell types that each express different genes. This contrasts withDrosophilawhere a single cell type expresses a number of genes expressing several such peptides. Whereas inDrosophilathe neuroendocrine cells producing insulin-like peptides also express sulfakinins, the arthropod orthologs of gastrin and cholecystokinin, inPeriplanetathe sulfakinins are produced by different cells. Other neuropeptides known to be produced by thepars intercerebralisinPeriplanetaand other insect species, such as the CRF-like diuretic hormone, neuroparsin, leucokinin or myosuppressin, neither colocalize with an insulin-related peptide. The separate cellular localization of these peptides and the existence of multiple insulin receptors in this species implies a more complex regulation by insulin and IGF-related peptides in cockroaches than in the fruit fly.
Use of an ultrasound picture archiving and communication system (PACS) to answer research questions: description of data cleaning methods
Authors: Moore Matthew K , Whalley Gillian , Jones Gregory T , Coffey Sean 
Published: December 2022

AbstractBackgroundUltrasound picture archiving and communication system (PACS) databases are useful for quality improvement and clinical research, but frequently contain free text that is not easily readable. Here, we present a method to extract and clean a semi-structured echocardiography (cardiac ultrasound) PACS database.MethodsEchocardiography studies between 1 January 2010 and 31 December 2018 were extracted using a data mining tool. Numeric variables were recoded with extreme values excluded. Analysis of free text, including descriptions of the heart valves and right and left ventricular size and function, was performed using a rule-based system. Different levels of free text variables were initially identified using commonly used phrases, and then iteratively developed. Randomly selected sets of 100 studies were compared to the electronic health record to validate the data cleaning process.ResultsThe data validation step was performed three times in total, with the Cohen’s kappa ranging between 0.88 and 1.00 for the final set of data validation across all measures.ConclusionFree text cleaning of semi-structured PACS databases is possible using freely available open source software. The accuracy of this method is high, and the resulting dataset can be linked to administrative data to answer research questions. We present a method that could be used to answer clinical questions or to develop quality improvement initiatives.
Horizontal transmission of penicillin binding protein 1A caused a nationwide spread of β-lactam resistance in pneumococci
Authors: Nakano Satoshi , Fujisawa Takao , Chang Bin , Ito Yutaka , Kitamura Norikazu , Suga Shigeru , Matsumura Yasufumi , Yamamoto Masaki , Nagao Miki , Ohnishi Makoto , Sugai Motoyuki 
Published: December 2022

AbstractThe emergence and spread of drug-resistant bacteria continue to be a global crisis. The mechanism of the resistance spread via mobile genetic elements such as plasmids is well known, however, the impact of the natural transformation on the spread remains unclear.Streptococcus pneumoniaeis well known to be a transformable pathogen by natural competence and they become β-lactam resistance by the acquisition of chromosomal genetic elements including mutated PBPs by natural transformation. To trace the transmission of pneumococcal PBPs among nationwide pediatric population and analyze the impact of transformed PBPs to β-lactam resistance, we collected and analyzed more than 1300 isolates ofS. pneumoniaethrough nationwide surveillance study for pediatric pneumococcal diseases between 2012-2017 in Japan.We discovered a high prevalence of a specific PBP1A type (pbp1a-13) in β-lactam resistant pneumococci that had a 370SSMK substitution in their β-lactam binding SXXK motif, suggesting that thispbp1a-13 transferred horizontally between different clones resulting in emergence and spread of β-lactam resistant pneumococcal clones. Divergence dating analysis suggested thatpbp1a-13 was inserted into major resistant lineages in the early 1990s through the 2000s, before introduction of pneumococcal conjugate vaccines in Japan. Our additional analysis for pneumococcal isolates that were recovered in the 90s in Japan suggested thatpbp1a-13 in GPSC1 (serotype 19F-CC236) and GPSC14 (serotype 23F-CC242) isolates were the origin of the currently spreadpbp1a-13. We provide evidence ofpbp1ahorizontal transmission at a nationwide scale and highlight the importance of PBP profile monitoring for identifying the emergence and spread of resistant pneumococci lineages.
Isolation of highly purified genomic material from mitochondria of muscle tissue cells
Authors: Tatarkina M.A. , Lobanova V.V. , I.I. Kozenkov I.I. , Efimenko B.E. , Dzhigkaev A. K. , Popadin K.Y. , Gunbin K.V. , Goncharov A.G. 
Published: December 2022

AbstractIn this work, we adapted a method for isolation of a highly purified fraction of mitochondrial DNA from muscle tissues suitable for further sample preparation of libraries without an amplification step for sequencing tasks on various NGS platforms and a method for evaluating the purity of DNA from contamination by nuclear genome regions.We optimized several techniques7,8for enrichment of the mitochondrial fractions and purifying mtDNA. Here, we describe a protocol that allows getting from 80-100 mg of muscle tissues up to 1000 ng mtDNA, almost free from impurities of RNA and fragments of the nuclear genome.To assess the degree of purity of human mtDNA fraction from impurities of the nuclear genome, we adapted the PCR-screening technique7for the beta-actin gene region and AluSx-repeats in the human genome.This methodology avoids false-heteroplasmy calls (PCR biases or NUMT contamination) that occur when long-range PCR amplification is used for mtDNA enrichment.
Improved N- and O-Glycopeptide Identification using High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS)
Authors: Alagesan Kathirvel , Ahmed-Begrich Rina , Charpentier Emmanuelle 
Published: December 2022

AbstractMass spectrometry is the premier tool for identifying and quantifying site-specific protein glycosylation globally. Analysis of intact glycopeptides often requires an enrichment step, after which the samples remain highly complex and exhibit a broad dynamic range of abundance.Here, we evaluated the analytical benefits of high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to nano-liquid chromatography mass spectrometry (nLC-MS) for analyses of intact glycopeptide devoid of any enrichment step. We compared the effects of compensation voltage on the transmission of N- and O-glycopeptides derived from heterogeneous protein mixtures using two FAIMS devices. We comprehensively demonstrate the performance characteristics of the FAIMS device for glycopeptide analysis and recommend optimal electrode temperature and compensation voltage (CV) settings for N- and O-glycopeptide analysis.Under optimal CV settings, FAIMS-assisted gas-phase fractionation in conjunction with chromatographic reverse phase separation resulted in a 31% increase in the detection of both N- and O-glycopeptide compared to control experiments without FAIMS. Overall, our results demonstrate that FAIMS provides an alternative means to access glycopeptides without any enrichment providing an unbiased global glycoproteome landscape. In addition, our work provides the framework to verify ‘difficult-to-identify’ glycopeptide features.
Ancestry dynamics and trait selection in a designer cat breed
Authors: Kaelin Christopher B. , McGowan Kelly A. , Hutcherson Anthony D. , Delay John M. , Barsh Gregory S. 
Published: December 2022

SummaryThe Bengal cat breed was developed from intercrosses between the Asian leopard cat,Prionailurus bengalensis, and the domestic cat,Felis silvestris catus, with a last common ancestor 6 million years ago. Predicted to contain ~95% of their genome from domestic cats, regions of the leopard cat genome are thought to account for unique pelage traits and ornate color patterns of the Bengal breed, which are similar to those of ocelots and jaguars. We explore ancestry distribution and selection signatures in the Bengal breed using reduced representation and whole genome sequencing from 905 cats. Overall, leopard cat introgressions are reduced twofold from expectation and include examples of genetic incompatibility—reduced expression of a leopard cat gene in a domestic cat background—underlying the color traitsCharcoaland contributing to coat color variation. Leopard cat introgressions do not show strong signatures of selection; instead, selective sweeps in Bengal cats are associated with domestic, rather than leopard cat haplotypes, and harbor candidate genes for pelage and color pattern. We identify the molecular and phenotypic basis of one selective sweep as reduced expression of theFgfr2gene, which underliesGlitter, a desirable trait that affects hair texture and light reflectivity.