bluuebunny/crossref_metadata_2025_split huggingface dataset:
Good and bad lettuce leaf microbes? Unravelling the genetic architecture of the microbiome to inform plant breeding for enhanced food safety and reduced food waste
Authors: Damerum A , Arnold EC , Bernard V , Smith HK , Taylor G 
Published: August 2021

ABSTRACTLettuce is a high value food crop, consumed raw around the world. Engineering of the leaf microbiome could provide significant benefits for enhanced crop yield and stress resistance and help to reduce food waste caused by microbial spoilage. Lettuce leaves also act as a vector for human pathogens, implicated in several high-profile food-borne disease outbreaks. Since host genotype helps determine microbiome composition, we hypothesize that leaf surface traits can be defined that associate with ‘good’ bacterial microbiomes providing benefits to the crop and that ‘bad’ microbiomes, where spoilage organisms and human pathogens are abundant, can also be associated to underlying leaf genetics, providing key targets for future crop breeding. Using a Recombinant Inbred Line (RIL) population, we show that cultivated and wild parental genotypes differ with reduced bacterial diversity, larger leaves and fewer, larger stomata, smaller epidermal cells and more hydrophilic leaf surfaces found in the cultivated compared to wild lettuce. Functional analysis of the associated microbiome revealed increased abundance of genes associated with disease virulence for the cultivated lettuce genotype, suggesting domestication has had broad impacts on leaf and associated bacterial microbiome traits. We defined the core lettuce bacterial microbiome from 171 RILs, comprised of 45 taxa in the phyla Proteobacteria, Actinobacteria, Firmicutes, Chloroflexi and Deinococcus-Thermus. Leaf surface characteristics important in influencing bacterial diversity and abundance were identified as stomatal size (length and width), epidermal cell area and number and leaf surface hydrophobicity of the abaxial leaf surface. Quantitative trait loci (QTL) for leaf surface traits, frequently mapped alongside those for the extended phenotype of bacterial taxa abundance, including for human pathogensCampylobacterspp.,Escherichia-Shigellaspp.,Clostridiumspp. (LG 4, 5 and 6) and spoilage bacteria,Pseudomonasspp. (LG 1, 3, 4, 6 and 9). Candidate genes underlying these QTL were enriched in GO terms for cell wall assembly and modification, defence response, hormone-mediated signalling and biosynthesis and anatomical structure development. This work provides the first insight into the genetic architecture of host surface traits in a leafy crop alongside the mapped genetic architecture of bacterial communities and has identified areas of the lettuce genome as important targets for future microbiome engineering.
Shotgun proteomic profiling of dormant, ‘non-culturable’Mycobacterium tuberculosis
Authors: Nikitushkin V. , Shleeva M. , Loginov D. , Dycka F. , Sterba J. , Kaprelyants A. 
Published: August 2021

AbstractDormant cells ofMycobacterium tuberculosis, in addition to low metabolic activity and a high level of drug resistance, are characterized by ‘non-culturability’ – a specific reversible state of the inability of the cells to grow on solid media. The biochemical characterization of this physiological state of the pathogen is only superficial, pending clarification of the metabolic processes that may exist in such cells. In this study, applying LC-MS proteomic profiling, we report the analysis of proteins accumulated in dormant, ‘non-culturable’M. tuberculosiscells in anin vitromodel of self-acidification of mycobacteria in the post-stationary phase, simulating thein vivopersistence conditions. This approach revealed the accumulation of a significant number of proteins (1379) in cells after 4 months of storage in dormancy; among them, 468 proteins were significantly different from those in the actively growing cells and bore a positive fold change (FC). Differential analysis revealed the proteins of the pH-dependent regulatory system phoP and allowed the reconstruction of the reactions of central carbon/glycerol metabolism, as well as revealing the salvaged pathways of mycothiol and UMP biosynthesis, establishing the cohort of survival enzymes of dormancy. The annotated pathways mirror the adaptation of the mycobacterial metabolic machinery to life within lipid-rich macrophages, especially the involvement of the methyl citrate and glyoxylate pathways. Thus, the currentin vitromodel ofM. tuberculosisself-acidification reflects the biochemical adaptation of these bacteria to persistencein vivo. Comparative analysis with published proteins with antigenic properties makes it possible to distinguish immunoreactive proteins (40) among the proteins bearing a positive FC in dormancy, which may include specific antigens of latent tuberculosis. Additionally, the biotransformatory enzymes (oxidoreductases and hydrolases) capable of prodrug activation and stored up in the dormant state were annotated. These findings may potentially lead to the discovery of immunodiagnostic tests for early latent tuberculosis and trigger the discovery of efficient drugs/prodrugs with potency against non-replicating, dormant populations of mycobacteria.
In vitro activity of bedaquiline and imipenem against actively growing, nutrient-starved, and intracellular Mycobacterium abscessus
Authors: Martins Olumide , Lee Jin , Kaushik Amit , Ammerman Nicole C. , Dooley Kelly E. , Nuermberger Eric L. 
Published: August 2021

AbstractMycobacterium abscessus lung disease is difficult to treat due to intrinsic drug resistance and the persistence of drug-tolerant bacteria. Currently, the standard of care is a multi-drug regimen with at least 3 active drugs, preferably including a β-lactam (imipenem or cefoxitin). These regimens are lengthy, toxic, and have limited efficacy. The search for more efficacious regimens led us to evaluate bedaquiline, a diarylquinoline licensed for treatment of multidrug-resistant tuberculosis. We performed in vitro time-kill experiments to evaluate the activity of bedaquiline alone and in combination with the first-line drug imipenem against M. abscessus under various conditions. Against actively growing bacteria, bedaquiline was largely bacteriostatic and antagonized the bactericidal activity of imipenem. Contrarily, against nutrient-starved persisters, bedaquiline was bactericidal, while imipenem was not, and bedaquiline drove the activity of the combination. In an intracellular infection model, bedaquiline and imipenem had additive bactericidal effects. Correlations between ATP levels and the bactericidal activity of imipenem and its antagonism by bedaquiline were observed. Interestingly, the presence of Tween 80 in the media affected the activity of both drugs, enhancing the activity of imipenem and reducing that of bedaquiline. Overall, these results show that bedaquiline and imipenem interact differently depending on culture conditions. Previously reported antagonistic effects of bedaquiline on imipenem were limited to conditions with actively multiplying bacteria and/or the presence of Tween 80, whereas the combination was additive or indifferent against nutrient-starved and intracellular M. abscessus, where promising bactericidal activity of the combination suggests it may have a role in future treatment regimens.
Machine learning detects SARS-CoV-2 and variants rapidly on DNA aptamer metasurfaces
Authors: Torun Hulya , Bilgin Buse , Ilgu Muslum , Yanik Cenk , Batur Numan , Celik Suleyman , Ozturk Meric , Dogan Ozlem , Ergonul Onder , Solaroglu Ihsan , Can Fusun , Onbasli Mehmet Cengiz 
Published: August 2021

AbstractCOVID-19 is detected using reverse transcription polymerase chain reaction (RT-PCR) of nasal swabs. A very sensitive and rapid detection technique using easily-collected fluids like saliva must be developed for safe and precise mass testing. Here, we introduce a metasurface platform for direct sensing of COVID-19 from unprocessed saliva. We computationally screen gold metasurfaces out of a pattern space of 2100 combinations for strongly-enhanced light-virus interaction with machine learning and use it to investigate the presence and concentration of the SARS-CoV-2. We use machine learning to identify the virus from Raman spectra with 95.2% sensitivity and specificity on 36 PCR positive and 33 negative clinical samples and to distinguish wild-type, alpha, and beta variants. Our results could pave the way for effective, safe and quantitative preventive screening and identification of variants.
COVID-19 in Brazilian children and adolescents: findings from 21 hospitals
Authors: Liu Priscila Menezes Ferri , de Melo Maria do Carmo Barros , Diniz Lilian Martins Oliveira , Dias Cristiane dos Santos , de Moura Costa André Soares , Farace Bárbara Lopes , da Silva Carla Thais Candida Alves , Anschau Fernando , Aranha Fernando Graça , Nascimento Guilherme Fagundes , Duani Helena , Costa Jamille Hemétrio Salles Martins , Ruschel Karen Brasil , Nogueira Matheus Carvalho Alves , de Oliveira Neimy Ramos , Pozza Roberta , Francisco Saionara Cristina , Lage Thalita Martins , Ramires Yuri Carlotto , Pereira Daniella Nunes , Reis Zilma Silveira Nogueira , Chatkin José Miguel , Marcolino Milena Soriano 
Published: August 2021

AbstractIntroductionChildren and adolescents with Covid-19 have been shown lower mortality less intense symptoms when compared to adults, but studies in Brazil have been based on the compulsory notifying system only.ObjectiveTo analyse clinical, laboratory, radiological characteristics and outcomes of hospitalized patients under 20 years with Covid-19.MethodsCases series of hospitalized patients with confirmed Covid-19 under 20 years, obtained from a cohort study in 37 hospitals from five states of Brazil.ResultsFrom 36 patients, 20 (55.5%) were adolescentes, 20 (55.5%) were male, 18 (50.0%) had comorbidities, 2 were pregnant and in 7 (19.4%), initial symptoms occurred during hospitalization for other causes, of whom 3 were possibly infected in the hospital. Fever (61.1%), dyspnea (33.3%) and neurological symptoms (33.0%) were the most common complaints. C-reactive protein was higher than 50mg/L in 16.7% and D-dimer was above the reference limit in 22.2%. Chest X-rays were performed in 20 (55.5%) patients, 9 had abnormalities, and chest tomography in 5. Hospital length of stay ranged from 1-40 days (median 5 [interquartile range 3-10]), 16 (44.4%) needed intensive therapy, 6 (16.7%) required mechanical ventilation and one patient (2.8%) died.ConclusionIn case series patients under 20 years from hospitals from 5 states of Brazil, comorbidities were frequent, and most common symptoms were fever, dyspnea and neurological symptoms. Forty-four percent required intensive therapy, showing that the disease was not as mild as it was expected, and one patient died.
Immunogenicity of BNT162b2 vaccine Against the Alpha and Delta Variants in Immunocompromised Patients
Authors: Hadjadj Jérome , Planas Delphine , Ouedrani Amani , Buffier Solene , Delage Laure , Nguyen Yann , Bruel Timothée , Stolzenberg Marie-Claude , Staropoli Isabelle , Ermak Natalia , Macraigne Laure , Morbieu Caroline , Henriquez Soledad , Veyer David , Péré Hélène , Casadevall Marion , Mouthon Luc , Rieux-Laucat Frédéric , Chatenoud Lucienne , Schwartz Olivier , Terrier Benjamin 
Published: August 2021

AbstractBackgroundThe emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. To what extent Delta evades vaccine-induced immunity in immunocompromised individuals with systemic inflammatory diseases remains unclear.MethodsWe conducted a prospective study in patients with systemic inflammatory diseases (cases) and controls receiving two doses of BNT162b2. Primary end points were anti-spike antibodies levels and cross-neutralization of Alpha and Delta variants after BNT162b2 vaccine. Secondary end points were T-cell responses, breakthrough infections and safety.ResultsSixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analyzed. Kinetics of anti-spike IgG and IgA after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralizing response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralized Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralizing activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after 2 doses of BNT162b2.ConclusionsRituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals (Funded by the Fonds IMMUNOV;ClinicalTrials.govnumber,NCT04870411).
The effect of eye protection on SARS-CoV-2 transmission: a systematic review
Authors: Byambasuren Oyungerel , Beller Elaine , Clark Justin , Collignon Peter , Glasziou Paul 
Published: August 2021

AbstractBackgroundThe effect of eye protection to prevent SARS-CoV-2 infection in the real-world remains uncertain. We aimed to synthesize all available research on the potential impact of eye protection on transmission of SARS-CoV-2.MethodsWe searched PROSPERO, PubMed, Embase, The Cochrane Library for clinical trials and comparative observational studies in CENTRAL, and Europe PMC for pre-prints. We included studies that reported sufficient data to estimate the effect of any form of eye protection including face shields and variants, goggles, and glasses, on subsequent confirmed infection with SARS-CoV-2.FindingsWe screened 898 articles and included 6 reports of 5 observational studies from 4 countries (USA, India, Columbia, and United Kingdom) that tested face shields, googles and wraparound eyewear on 7567 healthcare workers. The three before-and-after and one retrospective cohort studies showed statistically significant and substantial reductions in SARS-CoV-2 infections favouring eye protection with odds ratios ranging from 0.04 to 0.6, corresponding to relative risk reductions of 96% to 40%. These reductions were not explained by changes in the community rates. However, the one case-control study reported odds ratio favouring no eye protection (OR 1.7, 95% CI 0.99, 3.0). The high heterogeneity between studies precluded any meaningful meta-analysis. None of the studies adjusted for potential confounders such as other protective behaviours, thus increasing the risk of bias, and decreasing the certainty of evidence to very low.InterpretationCurrent studies suggest that eye protection may play a role in prevention of SARS-CoV-2 infection in healthcare workers. However, robust comparative trials are needed to clearly determine effectiveness of eye protections and wearability issues in both healthcare and general populations.FundingThere was no funding source for this study. All authors had full access to all data and agreed to final manuscript to be submitted for publication.
A novel method for robust estimation of ants’ walking speed and curvature on convoluted trajectories derived from their gait pattern
Authors: Choi Jibeom , Kim Woojoo , Song Woncheol , Lee Sang-im , Jablonski Piotr Grzegorz 
Published: August 2021

AbstractAccurate measurements of travel distance and speed are crucial for the analysis of animal movements. Measuring the movements of ants entails measuring the change in locations registered at time intervals. This process involves dilemma of setting the proper time window: a short time window is vulnerable to spatial errors in observation, while a long time window leads to underestimation of the travel distance. To overcome these difficulties, we propose a novel algorithm that successively interpolates two consecutive points of ant’s trajectory for a given time window by embracing the alternating tripod gait of ants. We demonstrate that this algorithm is more reliable compared to the conventional method of travel distance estimation based on the sum of the consecutive straight-line displacements (SLD). After obtaining speed estimates for a range of sampling time windows, we applied a fitting method that can estimate the actual speed without prior knowledge of spatial error distribution. We compared results from several methods of speed and curvature extracted from the empirical data of ant trajectories. We encourage empirical scientists to utilize the proposed methods rather than the conventional SLD method of speed estimation as this process is a more reliable and subjective selection of the sampling time window can be avoided.
Modeling the C. elegans Germline Stem Cell Genetic Network using Automated Reasoning
Authors: Amar Ani , Hubbard E. Jane Albert , Kugler Hillel 
Published: August 2021

ABSTRACTComputational methods and tools are a powerful complementary approach to experimental work for studying regulatory interactions in living cells and systems. We demonstrate the use of formal reasoning methods as applied to the Caenorhabditis elegans germ line, which is an accessible model system for stem cell research. The dynamics of the underlying genetic networks and their potential regulatory interactions are key for understanding mechanisms that control cellular decision-making between stem cells and differentiation. We model the “stem cell fate” versus entry into the “meiotic development” pathway decision circuit in the young adult germ line based on an extensive study of published experimental data and known/hypothesized genetic interactions. We apply a formal reasoning framework to derive predictive networks for control of differentiation. Using this approach we simultaneously specify many possible scenarios and experiments together with potential genetic interactions, and synthesize genetic networks consistent with all encoded experimental observations. In silico analysis of knock-down and overexpression experiments within our model recapitulate published phenotypes of mutant animals and can be applied to make predictions on cellular decision-making. This work lays a foundation for developing realistic whole tissue models of the C. elegans germ line where each cell in the model will execute a synthesized genetic network.
Cell type determination for cardiac differentiation occurs soon after seeding of human induced pluripotent stem cells
Authors: Jiang Connie L. , Goyal Yogesh , Jain Naveen , Wang Qiaohong , Truitt Rachel E. , Coté Allison J. , Emert Benjamin , Mellis Ian A. , Kiani Karun , Yang Wenli , Jain Rajan , Raj Arjun 
Published: August 2021

AbstractCardiac directed differentiation of human induced pluripotent stem cells consistently produces a mixed population of cardiomyocytes and non-cardiac cell types even when using very well-characterized protocols. We wondered whether differentiated cell types might result from intrinsic differences in hiPS cells prior to the onset of differentiation. By associating individual differentiated cells that share a common hiPS cell precursor, we were able to test whether expression variability in differentiated cells was pre-determined from the hiPS cell state. Although within a single experiment, differentiated cells that share an hiPS cell progenitor were more transcriptionally similar to each other than to other cells in the differentiated population, when the same hiPS cells were differentiated in parallel, we did not observe high transcriptional similarity across differentiations. Additionally, we found that substantial cell death occurred during differentiation in a manner that suggested that all cells were equally likely to survive or die, suggesting that there was no intrinsic selection bias for cells descended from particular hiPS cell progenitors. These results led us to wonder about how cells grow out spatially during the directed differentiation process. Labeling cells by their expression of a few canonical cell type marker genes, we showed that cells expressing the same marker tended to occur in patches observable by visual inspection, suggesting that cell type determination across multiple cell types, once initiated, is maintained in a cell-autonomous manner for multiple divisions. Altogether, our results show that while there is substantial heterogeneity in the initial hiPS cell population, that heterogeneity is not responsible for heterogeneous outcomes, and that the window during which cell type specification occurs is likely to begin shortly after the seeding of hiPS cells for differentiation.
Empirical Transmit Field Bias Correction of T1w/T2w Myelin Maps
Authors: Glasser Matthew F. , Coalson Timothy S. , Harms Michael P. , Xu Junqian , Baum Graham L. , Autio Joonas A. , Auerbach Edward J. , Greve Douglas N. , Yacoub Essa , Van Essen David C. , Bock Nicholas A. , Hayashi Takuya 
Published: August 2021

AbstractT1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a ‘pseudo-transmit’ approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.