bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contact tracing efficiency, transmission heterogeneity, and accelerating COVID-19 epidemics
Authors: Gardner Billy J. , Kilpatrick A. Marm 
Published: September 2020

AbstractSimultaneously controlling COVID-19 epidemics and limiting economic and societal impacts presents a difficult challenge, especially with limited public health budgets. Testing, contact tracing, and isolating/quarantining is a key strategy that has been used to reduce transmission of SARS-CoV-2, the virus that causes COVID-19. However, manual contact tracing is a time-consuming process and as case numbers increase it takes longer to reach each cases’ contacts, leading to additional virus spread. Delays between symptom onset and being tested (and receiving results), and a low fraction of symptomatic cases being tested and traced can also reduce the impact of contact tracing on transmission. We examined the relationship between cases and delays and the pathogen reproductive number Rt, and the implications for infection dynamics using a stochastic compartment model of SARS-CoV-2. We found that Rt increases sigmoidally with the number of cases due to decreasing contact tracing efficacy. This relationship results in accelerating epidemics because Rt increases, rather than declines, as infections increase. Shifting contact tracers from locations with high and low case burdens relative to capacity to locations with intermediate case burdens maximizes their impact in reducing Rt (but minimizing total infections is more complicated). Contact tracing efficacy also decreased with increasing delays between symptom onset and tracing and with lower fraction of symptomatic infections being tested. Finally, testing and tracing reductions in Rt can sometimes greatly delay epidemics due to the highly heterogeneous transmission dynamics of SARS-CoV-2. These results demonstrate the importance of having an expandable or mobile team of contact tracers that can be used to control surges in cases, and the value of easy access, high testing capacity and rapid turn-around of testing results, as well as outreach efforts to encourage symptomatic infections to be tested immediately after symptom onset.Author SummaryA key tool in the control of infectious diseases is contact tracing – the identification of individuals who have contacted the case and may have been infected by a newly detected case. However, to successfully contact and quarantine individuals requires time, and as cases rise, this can result in delays in reaching contacts during which time they may infect other people. Here we examine the quantitative relationships between increasing case numbers, contact tracing efficiency, and the pathogen reproductive number Rt (the number of cases infected by each case) and how these relationships vary with delays and incomplete participation in the testing and tracing process. We built
Efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Northern Papua and Jambi, Indonesia
Authors: Asih Puji BS , Rozi Ismail E , Dewayanti Farahana K , Wangsamuda Suradi , Zulfah Syarifah , Robaha Marthen , Hutahaean Jonny , Anggraeni Nancy D , Kusumaningsih Marti , Mulyani Pranti S , Sariwati Elvieda , Basri Herdiana H , Bustos Maria Dorina G , Syafruddin Din 
Published: September 2020

ABSTRACTDihydroartemisinin-piperaquine (DHA-PPQ) has been adopted as first-line therapy for uncomplicated falciparum malaria in Indonesia since 2010. The efficacy of DHA-PPQ was evaluated in 2 sentinel sites in Keerom District, Papua and Merangin District, Jambi Provinces from April 2017 to April 2018. Clinical and parasitological parameters were monitored over a 42-day period following the WHO standard in vivo protocol and subjects meeting the inclusion criteria were treated with DHA-PPQ once daily for 3 days, administered orally. In Keerom District, 6339 subjects were screened through active and passive cases detection. A total of 114 subjects infected by P. falciparum and 83 subjects infected by P. vivax agreed to take a part through written informed consent. Kaplan-Meier analysis of microscopy readings and PCR-corrected falciparum cases revealed a 93.1% (95%CI:86.4-97.2) and 97.9% (95%CI:92.7-99.7) DHA-PPQ efficacy, respectively and were classified as Adequate Clinical Parasitological Responses (ACPRs). For vivax malaria, the DHA-PPQ efficacy were 89% (95%CI: 80.2 - 94.9) and 100% (95%CI: 95.1-100) respectively. In Merangin District, 751 subjects were screened and 41 subjects infected by P. vivax were recruited. Microscopy reading and PCR-corrected analysis revealed a 97.4% (95%CI:86.2-99.9) and 100% (95%CI: 90.5-100) DHA-PPQ efficacy, respectively. No severe adverse events were found in both sites. In both sites, there was no delay in parasite clearance and no mutations in the PfK13 and PvK12 genes. Of the 6 recurrent P. falciparum found, 2 indicated recrudescent and 4 cases were re-infection. Analysis of the PfPM2 gene at day 0 and day of recurrence in recrudescent cases revealed the same single copy number, whereas 3 of the 4 re-infection cases carried 2-3 copy numbers. In conclusion, treatment of falciparum and vivax malaria cases with DHA-PPQ showed a high efficacy and safety. DHA-PPQ regimen is also efficacious against P. vivax cases in the absence of primaquine.
Embeddings from deep learning transfer GO annotations beyond homology
Authors: Littmann Maria , Heinzinger Michael , Dallago Christian , Olenyi Tobias , Rost Burkhard 
Published: September 2020

AbstractKnowing protein function is crucial to advance molecular and medical biology, yet experimental function annotations through the Gene Ontology (GO) exist for fewer than 0.5% of all known proteins. Computational methods bridge this sequence-annotation gap typically through homology-based annotation transfer by identifying sequence-similar proteins with known function or through prediction methods using evolutionary information. Here, we propose predicting GO terms through annotation transfer based on proximity of proteins in the SeqVec embedding rather than in sequence space. These embeddings originate from deep learned language models (LMs) for protein sequences (SeqVec) transferring the knowledge gained from predicting the next amino acid in 33 million protein sequences. Replicating the conditions of CAFA3, our method reaches an Fmaxof 37±2%, 50±3%, and 57±2% for BPO, MFO, and CCO, respectively. Numerically, this appears close to the top ten CAFA3 methods. When restricting the annotation transfer to proteins with <20% pairwise sequence identity to the query, performance drops (FmaxBPO 33±2%, MFO 43±3%, CCO 53±2%); this still outperforms naïve sequence-based transfer. Preliminary results from CAFA4 appear to confirm these findings. Overall, this new concept is likely to change the annotation of proteins, in particular for proteins from smaller families or proteins with intrinsically disordered regions.
The interplay of wind and uplift facilitates over-water flight in facultative soaring birds
Authors: Nourani Elham , Bohrer Gil , Becciu Paolo , Bierregaard Richard O. , Duriez Olivier , Figuerola Jordi , Gangoso Laura , Giokas Sinos , Higuchi Hiroyoshi , Kassara Christina , Kulikova Olga , Lecomte Nicolas , Monti Flavio , Pokrovsky Ivan , Sforzi Andrea , Therrien Jean-François , Tsiopelas Nikos , Vansteelant Wouter M.G. , Viana Duarte S. , Yamaguchi Noriyuki M. , Wikelski Martin , Safi Kamran 
Published: September 2020

AbstractFlying over the open sea is energetically costly for terrestrial birds. Despite this, over-water journeys of many birds, sometimes hundreds of kilometers long, are uncovered by bio-logging technology. To understand how these birds afford their flights over the open sea, we investigated the role of atmospheric conditions, specifically wind and uplift, in subsidizing over-water flight at the global scale. We first established that ΔT, the temperature difference between sea surface and air, is a meaningful proxy for uplift over water. Using this proxy, we showed that the spatio-temporal patterns of sea-crossing in terrestrial migratory birds is associated with favorable uplift conditions. We then analyzed route selection over the open sea for five facultative soaring species, representing all major migratory flyways. The birds maximized wind support when selecting their sea-crossing routes and selected higher uplift when suitable wind support was available. They also preferred routes with low long-term uncertainty in wind conditions. Our findings suggest that, in addition to wind, uplift may play a key role in the energy seascape for bird migration that in turn determines strategies and associated costs for birds crossing ecological barriers such as the open sea.
Effects of phylogeny on coexistence in model communities
Authors: Serván Carlos A. , Capitán José A. , Miller Zachary R. , Allesina Stefano 
Published: September 2020

AbstractA species’ traits influence the way in which it interacts with the environment. Thus, we expect traits to play a role in determining whether a given set of species coexists. Traits are, in turn, the outcome of an eco-evolutionary process summarized by a phylogenetic tree. Therefore, the phylogenetic tree associated with a set of species should encode information about the assembly properties of the community. Many studies have high-lighted the potentially complex ways in which phylogenetic information is translated into species’ ecological properties. However, much less emphasis has been placed on developing expectations for community properties under a particular hypothesis.In this work, we couple a simple model of trait evolution on a phylogenetic tree with local community dynamics governed by Lotka-Volterra equations. This allows us to derive properties of the community of coexisting species as a function of the number of traits, tree topology and the size of the species pool. Our results highlight how phylogenies and traits, in concert, affect the coexistence of a set of species.In this way, our work provides new baseline expectations for the ways in which phylogenetic information is reflected in the structure of and coexistence within local communities.
Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection
Authors: Moore Anne C. , Dora Emery G. , Peinovich Nadine , Tucker Kiersten P. , Lin Karen , Cortese Mario , Tucker Sean N. 
Published: September 2020

SUMMARYThere is an urgent need to develop efficacious vaccines against SARS-CoV-2 that also address the issues of deployment, equitable access, and vaccine acceptance. Ideally, the vaccine would prevent virus infection and transmission as well as preventing COVID-19 disease. We previously developed an oral adenovirus-based vaccine technology that induces both mucosal and systemic immunity in humans. Here we investigate the immunogenicity of a range of candidate adenovirusbased vaccines, expressing full or partial sequences of the spike and nucleocapsid proteins, in mice. We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Antigen-specific CD4+ and CD8+ T cells were induced by this leading vaccine candidate at low and high doses. This fulllength spike antigen plus nucleocapsid adenovirus construct has been prioritized for further clinical development.
Self-Supervised Contrastive Learning of Protein Representations By Mutual Information Maximization
Authors: Lu Amy X. , Zhang Haoran , Ghassemi Marzyeh , Moses Alan 
Published: September 2020

AbstractPretrained embedding representations of biological sequences which capture meaningful properties can alleviate many problems associated with supervised learning in biology. We apply the principle of mutual information maximization between local and global information as a self-supervised pretraining signal for protein embeddings. To do so, we divide protein sequences into fixed size fragments, and train an autoregressive model to distinguish between subsequent fragments from the same protein and fragments from random proteins. Our model, CPCProt, achieves comparable performance to state-of-the-art self-supervised models for protein sequence embeddings on various downstream tasks, but reduces the number of parameters down to 2% to 10% of benchmarked models. Further, we explore how downstream assessment protocols affect embedding evaluation, and the effect of contrastive learning hyperparameters on empirical performance. We hope that these results will inform the development of contrastive learning methods in protein biology and other modalities.
An early Cambrian ecdysozoan with a terminal mouth but no anus
Authors: Liu Yunhuan , Zhang Huaqiao , Xiao Shuhai , Shao Tiequan , Duan Baichuan 
Published: September 2020

ABSTRACTThe ecdysozoans are the most diverse animal group on Earth1, 2. Molecular clock studies indicate that the ecdysozoans may have diverged and diversified in the Ediacaran Period3, 4, but unambiguous ecdysozoan fossils first appear in the earliest Cambrian and are limited to cycloneuralians5–7. Here we report new material of the early Cambrian microscopic animalSaccorhytus coronarius, which was previously interpreted as a deuterostome8.Saccorhytus coronariusis reconstructed as a millimetric and ellipsoidal meiobenthic animal with a spinose armor and an anterior mouth but no anus. Purported pharyngeal gills in support of the deuterostome hypothesis8are shown to be taphonomic artifacts. Phylogenetic analyses indicate thatSaccorhytus coronariusbelongs to the total-group Ecdysozoa, highlighting the morphological and ecological diversity of early Cambrian ecdysozoans.
The association between COVID-19 and preterm delivery: A cohort study with a multivariate analysis
Authors:   Spanish Obstetric Emergency Group, Pérez Oscar Martínez 
Published: September 2020

Structured AbstractObjectiveTo determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity.Design and settingThroughout Spain, 45 hospitals took part in universal screening of pregnant women going into labour using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020.MethodsThe cohort of exposed and unexposed pregnancies was followed up until 6-weeks post-partum. Multivariate logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of COVID-19 exposure, compared to non-exposure, with infection-related obstetric outcomes.Main outcome measuresPreterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions.ResultsIn the cohort of 1,009 screened pregnancies, 246 were COVID-19 positive. Compared to non-exposure, COVID-19 exposure increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32–3.36, p = 0.002), premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11–2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43 – 8.94, p< 0.001).ConclusionThis first prospective cohort study demonstrated that pregnant women infected with SARS- CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research.
Discovery of a Potent and Dual-Selective Bisubstrate Inhibitor for Protein Arginine Methyltransferase 4/5
Authors: Al-Hamashi Ayad A. , Chen Dongxing , Deng Youchao , Dong Guangping , Huang Rong 
Published: September 2020

AbstractProtein arginine methyltransferases (PRMTs) have been implicated in the progression of many diseases. Understanding substrate recognition and specificity of individual PRMT would facilitate the discovery of selective inhibitors towards future drug discovery. Herein, we reported the design and synthesis of bisubstrate analogues for PRMTs that incorporate a S-adenosylmethionine (SAM) analogue moiety and a tripeptide through an alkyl substituted guanidino group. CompoundAH237is a potent and selective inhibitor for PRMT4 and PRMT5 with a half-maximal inhibition concentration (IC50) of 2.8 nM and <1.5 nM, respectively. Computational studies provided a plausible explanation for the high potency and selectivity ofAH237for PRMT4/5 over other 40 methyltransferases. This proof-of-principle study outlines an applicable strategy to develop potent and selective bisubstrate inhibitors for PRMTs, providing valuable probes for future structural studies.
Characterization of gustatory receptor 7 in the brown planthopper reveals functional versatility
Authors: Ojha Abhishek , Zhang Wenqing 
Published: September 2020

AbstractInsect pests consume tastants as their necessary energy and nutrient sources. Gustatory receptors play important roles in insect life and can form within an extremely complicated regulatory network. However, there are still many gustatory genes that have a significant impact on insect physiology, but their functional mechanism is still unknown. Here, we purified and characterized a gustatory receptor (protein) coding gene,NlGr7, from the brown planthopper (BPH)Nilaparvata lugens, which is an important insect pest of rice. Our results revealed thatNlGr7 has an active association with various ligands, such as lectins, lipids (phospho- and sphingolipid) and copper. The mass-spectrometry result showed thatNlGr7 is a sugar receptor, andNlGr7 is validated by different types of insoluble polysaccharides and a varied range of tastants. Furthermore, we observed thatNlGr7-bound ATP hydrolysed on the ATPase activity assay, which indicated thatNlGr7 may be associated with important biological functions in the BPH. The importantNlGr7 for chemoreception has now been characterized in the BPH. We showed thatNlGr7 in the BPH is required for various protein-ligands, as well as protein-sugars interactions, to play crucial roles in this pest. This study will provide valuable information for further functional studies of chemoreception mechanisms in this important agricultural pest.
BacAnt: A Combination Annotation Server for Bacterial DNA Sequences to Identify Antibiotic Resistance Genes, Integrons, and Transposable Elements
Authors: Hua Xiaoting , Liang Qian , Deng Min , He Jintao , Wang Meixia , Hong Wenjie , Wu Jun , Lu Bian , Leptihn Sebastian , Yu Yunsong , Chen Huan 
Published: September 2020

AbstractWhole genome sequencing (WGS) of bacteria has become a routine method in diagnostic laboratories. One of the clinically most useful advantages of WGS is the ability to predict antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) in bacterial sequences. This allows comprehensive investigations of such genetic features but can also be used for epidemiological studies. A plethora of software programs have been developed for the detailed annotation of bacterial DNA sequences, such as RAST (Rapid Annotation using Subsystem Technology), Resfinder, ISfinder, INTEGRALL and The Transposon Registry. Unfortunately, to this day, a reliable annotation tool of the combination of ARGs and MGEs is not available, and the generation of genbank files requires much manual input. Here, we present a new webserver which allows the annotation of ARGs, integrons, and transposable elements at the same time. The pipeline generates genbank files automatically, which are compatible with easyfig for comparative genomic analysis. Our BacAnt code and standalone software package are available athttps://github.com/xthua/bacantwith an accompanying web application athttp://bacant.net.Graphical Abstract
Transcription initiation mapping in 31 bovine tissues reveals complex promoter activity, pervasive transcription, and tissue-specific promoter usage
Authors: Goszczynski D.E. , Halstead M.M. , Islas-Trejo A.D. , Zhou H. , Ross P.J. 
Published: September 2020

ABSTRACTCharacterizing transcription start sites is essential for understanding the regulatory mechanisms that control gene expression. Recently, a new bovine genome assembly (ARS-UCD1.2) with high continuity, accuracy, and completeness was released; however, the functional annotation of the bovine genome lacks precise transcription start sites and contains a low number of transcripts in comparison to human and mouse. Using the RAMPAGE approach, this study identified transcription start sites at high resolution in a large collection of bovine tissues. We found several known and novel transcription start sites attributed to promoters of protein coding and lncRNA genes that were validated through experimental andin silicoevidence. With these findings, the annotation of transcription start sites in cattle reached a level comparable to the mouse and human genome annotations. In addition, we identified and characterized transcription start sites for antisense transcripts derived from bidirectional promoters, potential lncRNAs, mRNAs, and pre-miRNAs. We also analyzed the quantitative aspects of RAMPAGE to produce a promoter activity atlas, reaching highly reproducible results comparable to traditional RNA-seq. Co-expression networks revealed considerable use of tissue specific promoters, especially between brain and testicle, which expressed several genes in common from alternate loci. Furthermore, regions surrounding co-expressed modules were enriched in binding factor motifs representative of each tissue. The comprehensive annotation of promoters in such a large collection of tissues will substantially contribute to our understanding of gene expression in cattle and other mammalian species, shortening the gap between genotypes and phenotypes.
Functional metagenomics of bark microbial communities from avocado trees (Persea americana Mill.) reveals potential for bacterial primary productivity
Authors: Aguirre-von-Wobeser Eneas 
Published: September 2020

SummaryBark microbial communities are poorly understood, and information on the metabolic capacities of their inhabitants is lacking. Bark microbial communities share part of their taxonomic composition with soil, but the functional differences and similarities are unknown. By comparing bark microbial communities of avocado trees (Persea americana, Mill.) with rhizospheric soil, functional processes relevant to the bark environment were identified. DNA from bark and soil communities was extracted from the same trees, and shotgun metagenomics sequencing was performed using nextSeq technology. Genes were identified by BLAST methods, and functional annotation was performed with KEGG databases as a reference. Bacterial oxygenic and anoxygenic photosynthesis genes were highly abundant in bark as compared to soil. Furthermore, increased presence of nitrogenase genes suggests a potential for nitrogen fixation. Genes for methanol utilization were abundant in bark, but no evidence of methane utilization potential was observed. Bark microbial communities have the genetic information for potential primary productivity, which might contribute to microbial growth independent of plant-derived carbon substrates.