bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting the role of the human microbiome in COVID-19 via metagenome-assembled genomes
Authors: Ke Shanlin , Weiss Scott T. , Liu Yang-Yu 
Published: September 2022

AbstractCoronavirus disease 2019 (COVID-19), primarily a respiratory disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is often accompanied by gastrointestinal symptoms. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that most previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. Here we used whole-metagenome shotgun sequencing data together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from 514 COVID-19 related nasopharyngeal and fecal samples in six independent cohorts. We reconstructed a total of 11,584 medium-and high-quality microbial MAGs and obtained 5403 non-redundant MAGs (nrMAGs) with strain-level resolution. We found that there is a significant reduction of strain richness for many species in the gut microbiome of COVID-19 patients. The gut microbiome signatures can accurately distinguish COVID-19 cases from healthy controls and predict the progression of COVID-19. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. Finally, we demonstrated that the main findings of our study can be largely validated in three independent cohorts. The presented results highlight the importance of incorporating the human gut microbiome in our understanding of SARS-CoV-2 infection and disease progression.
Metagenomic and metatranscriptomic insights into sulfate-reducing bacteria in a revegetated acidic mine wasteland
Authors: Li Jin-tian , Jia Pu , Wang Xiao-juan , Ou Shu-ning , Yang Tao-tao , Feng Shi-wei , Lu Jing-li , Fang Zhou , Liu Jun , Liao Bin , Shu Wen-sheng , Liang Jie-Liang 
Published: September 2022

AbstractThe widespread occurrence of sulfate-reducing microorganisms (SRMs) in temporarily oxic/hypoxic aquatic environments indicates an intriguing possibility that SRMs can prevail in constantly oxic/hypoxic terrestrial sulfate-rich environments. However, little attention has been given to this possibility, leading to an incomplete understanding of microorganisms driving the terrestrial part of the global sulfur (S) cycle. In this study, genome-centric metagenomics and metatranscriptomics were employed to explore the diversity, metabolic potential, and gene expression profile of SRMs in a revegetated acidic mine wasteland under constantly oxic/hypoxic conditions. We recovered 16 medium- to high-quality metagenome-assembled genomes (MAGs) containing reductive dsrAB. Among them, 12 and four MAGs belonged to Acidobacteria and Deltaproteobacteria, respectively, harboring three new SRM genera. Comparative genomic analysis based on seven high-quality MAGs (completeness >90% and contamination <10%; including six acidobacterial and one deltaproteobacterial) and genomes of three additional cultured model species showed that Acidobacteria-related SRMs had more genes encoding glycoside hydrolases, oxygen-tolerant hydrogenases, and cytochrome c oxidases than Deltaproteobacteria-related SRMs. The opposite pattern was observed for genes encoding superoxide reductases and thioredoxin peroxidases. Using VirSorter, viral genome sequences were found in five of the 16 MAGs and in all three cultured model species. These prophages encoded enzymes involved in glycoside hydrolysis and antioxidation in their hosts. Moreover, metatranscriptomic analysis revealed that 15 of the 16 SRMs reported here were active in situ. An acidobacterial MAG containing a prophage dominated the SRM transcripts, expressing a large number of genes involved in its response to oxidative stress and competition for organic matter.
Practical tips in bronchiectasis for Primary Care
Authors: Martinez-Garcia Miguel Angel , Garcia-Ortega Alberto , Oscullo Grace 
Published: September 2022

AbstractBronchiectasis is the third most common chronic inflammatory airway disease, after chronic obstructive pulmonary disease (COPD) and asthma with a prevalence clearly underestimated probably because of its clinical similitudes with other chronic airway diseases. Bronchiectasis can be caused by a dozen of pulmonary and extra-pulmonary diseases and a variable number and severity of exacerbations can appear throughout its natural history, usually with an infectious profile. The dilation of the airway and the inflammation/infection is their radiological and pathophysiological hallmarks. Primary Care should play an important play in many aspects of the bronchiectasis assessment. In this article, we will try to offer a series of important concepts and practical tips on some key aspects of the diagnosis and management of bronchiectasis in Primary Care: clinical suspicion, diagnostic methods, severity assessment, overlap with asthma and COPD and microbiological and therapeutic aspects.
Composable end-to-end security of Gaussian quantum networks with untrusted relays
Authors: Ghalaii Masoud , Papanastasiou Panagiotis , Pirandola Stefano 
Published: September 2022

AbstractGaussian networks are fundamental objects in network information theory. Here many senders and receivers are connected by physically motivated Gaussian channels, while auxiliary Gaussian components, such as Gaussian relays, are entailed. Whilst the theoretical backbone of classical Gaussian networks is well established, the quantum analog is yet immature. Here, we theoretically tackle composable security of arbitrary Gaussian quantum networks, with generally untrusted nodes, in the finite-size regime. We put forward a general methodology for parameter estimation, which is only based on the data shared by the remote end-users. Taking a chain of identical quantum links as an example, we further demonstrate our study. Additionally, we find that the key rate of a quantum amplifier-assisted chain can ideally beat the fundamental repeaterless limit with practical block sizes. However, this objective is practically questioned leading the way to future network/chain designs.
Development of an attenuated vaccine against Koi Herpesvirus Disease (KHVD) suitable for oral administration and immersion
Authors: Klafack Sandro , Schröder Lars , Jin Yeonhwa , Lenk Matthias , Lee Pei-Yu , Fuchs Walter , Avarre Jean-Christophe , Bergmann Sven M. 
Published: September 2022

AbstractSince the end of the1990ies,Cyprinid herpesvirus 3(also known as koi herpesvirus, KHV) has caused mass mortality events of koi and common carp all over the globe. This induced a high economic impact, since the KHV disease cannot be cured up to now, but only prevented by vaccination. Unfortunately, there is only one commercial vaccine available which is not approved in most countries. Therefore, there is an urgent need for new, safe and available vaccines. In this study, a live attenuated vaccine virus was generated by cell culture passages of virulent KHV, and shown to protect carp or koi after immersion or oral application against wild type challenge. An advantage of boost immunization was demonstrated, especially after oral application. Vaccination induced no or mild clinical signs and protecting antibodies have been measured. Additionally, the vaccine virus allowed differentiation of infected from vaccinated animals (DIVA) by PCR. The attenuation of the newly generated vaccine was tracked down to a partial deletion of open reading frame 150. This was confirmed by the generation of engineered ORF150 deletion mutants of wild-type KHV which exhibited a similar attenuation in vivo.
Rational attenuation of RNA viruses with zinc finger antiviral protein
Authors: Gonçalves-Carneiro Daniel , Mastrocola Emily , Lei Xiao , DaSilva Justin , Chan Yoke Fun , Bieniasz Paul D. 
Published: September 2022

AbstractAttenuation of a virulent virus is a proven approach for generating vaccines but can be unpredictable. For example, synonymous recoding of viral genomes can attenuate replication but sometimes results in pleiotropic effects that confound rational vaccine design. To enable specific, conditional attenuation of viruses, we examined target RNA features that enable zinc finger antiviral protein (ZAP) function. ZAP recognized CpG dinucleotides and targeted CpG-rich RNAs for depletion, but RNA features such as CpG numbers, spacing and surrounding nucleotide composition that enable specific modulation by ZAP were undefined. Using synonymously mutated HIV-1 genomes, we defined several sequence features that govern ZAP sensitivity and enable stable attenuation. We applied rules derived from experiments with HIV-1 to engineer a mutant enterovirus A71 genome whose attenuation was stable and strictly ZAP-dependent, both in cell culture and in mice. The conditionally attenuated enterovirus A71 mutant elicited neutralizing antibodies that were protective against wild-type enterovirus A71 infection and disease in mice. ZAP sensitivity can thus be readily applied for the rational design of conditionally attenuated viral vaccines.
Impact of embryonic manipulations on core body temperature dynamics and survival in broilers exposed to cyclic heat stress
Authors: Ncho Chris Major , Goel Akshat , Gupta Vaishali , Jeong Chae-Mi , Choi Yang-Ho 
Published: September 2022

AbstractAmbient temperature-associated stress has been shown to affect the normal physiological functions of birds. The recent literature indicated that both, embryonic thermal manipulation (ETM) and in ovo feeding (IOF) of γ-aminobutyric acid (GABA) can mitigate the deleterious effects of heat stress (HS) in young broiler chicks. Therefore, this study intended to assess the effects of cyclic HS (32 ± 1 °C, 4 h/day from day 29 to 35) on rectal temperatures (RTs) and survival in broiler chickens after ETM and in IOF of GABA. A total of 275 RT data points and survival data were collected from chicks assigned to the following five treatments: chicks hatched from control eggs (CON); chicks hatched from control eggs but exposed to HS (CON + HS); chicks hatched from eggs injected at 17.5 days of incubation with 0.6 mL of 10% GABA and exposed to HS (G10 + HS); chicks hatched from thermally manipulated eggs (39.6 °C, 6 h/day from embryonic days 10 to 18) and exposed to HS (TM + HS); chicks hatched from eggs that received both previous treatments during incubation and exposed to HS (G10 + TM + HS). Under thermoneutral conditions, RTs increased quadratically from 39.9 ± 0.2 °C at hatching to 41.4 ± 0.1 °C at 8 days of age. When exposed to cyclic HS during the last week of rearing, the birds’ RTs tended to decrease at the end of the heat stress challenge (from 43.0 ± 0.2 °C on day 29 to 42.4 ± 0.1 °C on day 35). A stepwise Cox regression indicated that treatment was predictive of birds’ survival. Hazard ratios (HR) and their confidence intervals (CI) were calculated to assess the likelihood of death during the trial. The birds, belonging to the G10 + TM + HS group, were less likely to die under HS (HR 0.11, 95% CI 0.02 to 0.91, P = 0.041) compared to the CON + HS birds. Taken together, the combination of ETM and GABA IOF may help mitigate the drawbacks of cyclic HS by improving the survival of broilers.
A pocket-based 3D molecule generative model fueled by experimental electron density
Authors: Wang Lvwei , Bai Rong , Shi Xiaoxuan , Zhang Wei , Cui Yinuo , Wang Xiaoman , Wang Cheng , Chang Haoyu , Zhang Yingsheng , Zhou Jielong , Peng Wei , Zhou Wenbiao , Huang Bo 
Published: September 2022

AbstractWe report for the first time the use of experimental electron density (ED) as training data for the generation of drug-like three-dimensional molecules based on the structure of a target protein pocket. Similar to a structural biologist building molecules based on their ED, our model functions with two main components: a generative adversarial network (GAN) to generate the ligand ED in the input pocket and an ED interpretation module for molecule generation. The model was tested on three targets: a kinase (hematopoietic progenitor kinase 1), protease (SARS‐CoV‐2 main protease), and nuclear receptor (vitamin D receptor), and evaluated with a reference dataset composed of over 8000 compounds that have their activities reported in the literature. The evaluation considered the chemical validity, chemical space distribution-based diversity, and similarity with reference active compounds concerning the molecular structure and pocket-binding mode. Our model can generate molecules with similar structures to classical active compounds and novel compounds sharing similar binding modes with active compounds, making it a promising tool for library generation supporting high-throughput virtual screening. The ligand ED generated can also be used to support fragment-based drug design. Our model is available as an online service to academic users via https://edmg.stonewise.cn/#/create.
Study of gut microbiota alterations in Alzheimer's dementia patients from Kazakhstan
Authors: Kaiyrlykyzy Aiym , Kozhakhmetov Samat , Babenko Dmitriy , Zholdasbekova Gulnaz , Alzhanova Dinara , Olzhayev Farkhad , Baibulatova Aida , Kushugulova Almagul R. , Askarova Sholpan 
Published: September 2022

AbstractWe have investigated the diversity and composition of gut microbiotas isolated from AD (Alzheimer's disease) patients (n = 41) and healthy seniors (n = 43) from Nur-Sultan city (Kazakhstan). The composition of the gut microbiota was characterized by 16S ribosomal RNA sequencing. Our results demonstrated significant differences in bacterial abundance at phylum, class, order, and genus levels in AD patients compared to healthy aged individuals. Relative abundance analysis has revealed increased amount of taxa belonging to Acidobacteriota, Verrucomicrobiota, Planctomycetota and Synergistota phyla in AD patients. Among bacterial genera, microbiotas of AD participants were characterized by a decreased amount of Bifidobacterium, Clostridia bacterium, Castellaniella, Erysipelotrichaceae UCG-003, Roseburia, Tuzzerella, Lactobacillaceae and Monoglobus. Differential abundance analysis determined enriched genera of Christensenellaceae R-7 group, Prevotella, Alloprevotella, Eubacterium coprostanoligenes group, Ruminococcus, Flavobacterium, Ohtaekwangia, Akkermansia, Bacteroides sp. Marseille-P3166 in AD patients, whereas Levilactobacillus, Lactiplantibacillus, Tyzzerella, Eubacterium siraeum group, Monoglobus, Bacteroides, Erysipelotrichaceae UCG-003, Veillonella, Faecalibacterium, Roseburia, Haemophilus were depleted. We have also found correlations between some bacteria taxa and blood serum biochemical parameters. Adiponectin was correlated with Acidimicrobiia, Faecalibacterium, Actinobacteria, Oscillospiraceae, Prevotella and Christensenellaceae R-7. The Christensenellaceae R-7 group and Acidobacteriota were correlated with total bilirubin, while Firmicutes, Acidobacteriales bacterium, Castellaniella alcaligenes, Lachnospiraceae, Christensenellaceae and Klebsiella pneumoniae were correlated with the level of CRP in the blood of AD patients. In addition, we report the correlations found between disease severity and certain fecal bacteria. This is the first reported study demonstrating gut microbiota alterations in AD in the Central Asian region.
Determination for a suitable ratio of dried black pepper and cinnamon powder in the development of mixed-spice ice cream
Authors: Aumpa Pajaree , Khawsud Amita , Jannu Taruedee , Renaldi Gerry , Utama-Ang Niramon , Bai-Ngew Shitapan , Walter Ponjan , Samakradhamrongthai Rajnibhas Sukeaw 
Published: September 2022

AbstractBlack pepper powder (BPP) and cinnamon powder (CP) are traditionally used as food ingredients and can apply related to developing a functional product. In this study, BPP and CP were used as an ingredient in mixed-spice ice cream (MSIC). The physicochemical properties, textural properties, and sensory qualities were investigated as key points. BPP (0.51–17.49 g) and CP (8.79–51.21 g) were combined using a central composite design (CCD) with 2 centerpoints. The optimized BPP and CP for the MSIC were 15.00 g and 34.00 g, which exhibited firmness and overrun at 3210.65 ± 105.74 g.force and 61.63 ± 0.60%. The MSIC with optimized BPP and CP also provides high bioactive compounds and antioxidant activities with cinnamaldehyde and piperine as flavor characteristics. The findings indicated that BPP and CP can enhance the functional properties and provide alternative flavors in the food product, providing an innovative approach to deliver health-beneficial combinations for consumer satisfaction.
Circulating tumor DNA sequencing provides comprehensive mutation profiling for pediatric central nervous system tumors
Authors: Bonner Erin R. , Harrington Robin , Eze Augustine , Bornhorst Miriam , Kline Cassie N. , Gordish-Dressman Heather , Dawood Adam , Das Biswajit , Chen Li , Pauly Rini , Williams P. Mickey , Karlovich Chris , Peach Amanda , Howell D’andra , Doroshow James , Kilburn Lindsay , Packer Roger J. , Mueller Sabine , Nazarian Javad 
Published: September 2022

AbstractMolecular profiling of childhood CNS tumors is critical for diagnosis and clinical management, yet tissue access is restricted due to the sensitive tumor location. We developed a targeted deep sequencing platform to detect tumor driver mutations, copy number variations, and heterogeneity in the liquid biome. Here, we present the sensitivity, specificity, and clinical relevance of our minimally invasive platform for tumor mutation profiling in children diagnosed with CNS cancer.
Data-driven causal model discovery and personalized prediction in Alzheimer's disease
Authors: Zheng Haoyang , Petrella Jeffrey R. , Doraiswamy P. Murali , Lin Guang , Hao Wenrui ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2022

AbstractWith the explosive growth of biomarker data in Alzheimer’s disease (AD) clinical trials, numerous mathematical models have been developed to characterize disease-relevant biomarker trajectories over time. While some of these models are purely empiric, others are causal, built upon various hypotheses of AD pathophysiology, a complex and incompletely understood area of research. One of the most challenging problems in computational causal modeling is using a purely data-driven approach to derive the model’s parameters and the mathematical model itself, without any prior hypothesis bias. In this paper, we develop an innovative data-driven modeling approach to build and parameterize a causal model to characterize the trajectories of AD biomarkers. This approach integrates causal model learning, population parameterization, parameter sensitivity analysis, and personalized prediction. By applying this integrated approach to a large multicenter database of AD biomarkers, the Alzheimer’s Disease Neuroimaging Initiative, several causal models for different AD stages are revealed. In addition, personalized models for each subject are calibrated and provide accurate predictions of future cognitive status.
Precise identification of cancer cells from allelic imbalances in single cell transcriptomes
Authors: Trinh Mi K. , Pacyna Clarissa N. , Kildisiute Gerda , Thevanesan Christine , Piapi Alice , Ambridge Kirsty , Anderson Nathaniel D. , Khabirova Eleonora , Prigmore Elena , Straathof Karin , Behjati Sam , Young Matthew D. 
Published: September 2022

AbstractA fundamental step of tumour single cell mRNA analysis is separating cancer and non-cancer cells. We show that the common approach to separation, using shifts in average expression, can lead to erroneous biological conclusions. By contrast, allelic imbalances representing copy number changes directly detect the cancer genotype and accurately separate cancer from non-cancer cells. Our findings provide a definitive approach to identifying cancer cells from single cell mRNA sequencing data.
Engineered marble-like bovine fat tissue for cultured meat
Authors: Zagury Yedidya , Ianovici Iris , Landau Shira , Lavon Neta , Levenberg Shulamit 
Published: September 2022

AbstractCultured meat can provide a sustainable and more ethical alternative to conventional meat. Most of the research in this field has been focused on developing muscle tissue, as it is the main component of meat products, while very few studies address cultured fat tissue, an essential component in the human diet and determinant of meat quality, flavor, juiciness, and tenderness. Here, we engineered bovine fat tissue for cultured meat and incorporated it within engineered bovine muscle tissue. Mesenchymal stem cells (MSCs) were derived from bovine adipose tissue and exhibited the typical phenotypic profile of adipose-derived MSCs. MSC adipogenic differentiation and maturation within alginate-based three-dimensional constructs were optimized to yield a fat-rich edible engineered tissue. Subsequently, a marble-like construct, composed of engineered bovine adipose and muscle tissues, was fabricated, mimicking inter- and intra-muscular fat structures.
Fine-mapping and identification of candidate causal genes for tail length in the Merinolandschaf breed
Authors: Lagler Dominik Karl , Hannemann Elisabeth , Eck Kim , Klawatsch Jürgen , Seichter Doris , Russ Ingolf , Mendel Christian , Lühken Gesine , Krebs Stefan , Blum Helmut , Upadhyay Maulik , Medugorac Ivica 
Published: September 2022

AbstractDocking the tails of lambs in long-tailed sheep breeds is a common practice worldwide. But this practice is associated with pain. Breeding for a shorter tail could offer an alternative. Therefore, this study aimed to analyze the natural tail length variation in the Merinolandschaf and to identify causal alleles for the short tail phenotype segregating within long-tailed breeds. We used SNP-based association analysis and haplotype-based mapping in 362 genotyped (Illumina OvineSNP50) and phenotyped Merinolandschaf lambs. Genome-wide significant regions were capture sequenced in 48 lambs and comparatively analyzed in various long and short-tailed sheep breeds and wild sheep subspecies. Here we show a SNP located in the first exon of HOXB13 and a SINE element located in the promotor of HOXB13 as promising candidates. These results enable more precise breeding towards shorter tails, improve animal welfare by amplification of ancestral alleles and contribute to a better understanding of differential embryonic development.
LDLR, LRP1, and Megalin redundantly participate in the uptake of Clostridium novyi alpha-toxin
Authors: Zhou Yao , Li Danyang , Li Diyin , Chen Aizhong , He Liuqing , Luo Jianhua , Tao Liang 
Published: September 2022

AbstractClostridium novyi alpha-toxin (Tcnα) is a potent exotoxin that induces severe symptoms including gas gangrene, myositis, necrotic hepatitis, and sepsis. Tcnα binds to sulfated glycosaminoglycans (sGAG) for cell-surface attachment and utilizes low-density lipoprotein receptor (LDLR) for rapid entry. However, it was also shown that Tcnα may use alternative entry receptors other than LDLR. Here, we define that LRP1 and Megalin can also facilitate the cellular entry of Tcnα by employing reconstitutive LDLR family proteins. LDLR, LRP1, and Megalin recognize Tcnα via their ligand-binding domains (also known as LDL receptor type A repeats). Notably, LDLR and LRP1 have contrasting expression levels in many different cells, thus the dominant entry receptor for Tcnα could be cell-type dependent. These findings together increase our knowledge of the Tcnα actions and further help to understand the pathogenesis of C. novyi infection-associated diseases.