bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Neural Networks can Predict Incident Atrial Fibrillation from the 12-lead Electrocardiogram and may help Prevent Associated Strokes
Authors: Raghunath Sushravya , Pfeifer John M. , Ulloa-Cerna Alvaro E. , Nemani Arun , Carbonati Tanner , Jing Linyuan , vanMaanen David P. , McCarty Bern E. , Hartzel Dustin N. , Ruhl Jeffery A. , Stoudt Nathan J. , Johnson Kipp W. , Zimmerman Noah , Leader Joseph B. , Kirchner H. Lester , Griessenauer Christoph , Hafez Ashraf , Good Christopher W. , Fornwalt Brandon K. , Haggerty Christopher M. 
Published: April 2020

AbstractBackgroundAtrial fibrillation (AF) is associated with substantial morbidity, especially when it goes undetected. If new onset AF could be predicted, targeted population screening could be used to find it early. We hypothesized that a deep neural network could predict new onset AF from the resting 12-lead electrocardiogram (ECG) and that this prediction may help prevent AF-related stroke.MethodsWe used 1.6M resting 12-lead ECG voltage-time traces from 430k patients collected from 1984-2019 in this study. Deep neural networks were trained to predict new onset AF (within 1 year) in patients without a history of AF. Performance was evaluated using areas under the receiver operating characteristic curve (AUROC) and precision-recall curve (AUPRC). We performed an incidence-free survival analysis for a period of 30 years following the ECG stratified by model predictions. To simulate real-world deployment, we trained a separate model using all ECGs prior to 2010 and evaluated model performance on a test set of ECGs from 2010 through 2014 that were linked to our stroke registry. We used standard metrics to explore different prediction thresholds for the model and also calculated how many AF-related strokes might be potentially prevented.ResultsThe AUROC and AUPRC were 0.83 and 0.21, respectively, for predicting new onset AF within 1 year of an ECG. Adding age and sex improved the AUROC to 0.85 and the AUPRC to 0.23. The hazard ratio for the predicted high- vs. low-risk groups over a 30-year span was 7.2 [95% confidence interval: 6.9 – 7.6]. In a simulated deployment scenario, using the F2 score to select the risk prediction threshold, the model predicted new onset AF at 1 year with a sensitivity of 69%, specificity of 81%, and positive predictive value (PPV) of 12%. This model correctly predicted new onset AF in 62% of all patients that experienced an AF-related stroke within 3 years of the ECG.ConclusionsDeep learning can predict new onset AF from the 12-lead ECG in patients with no prior history of AF. This prediction may prove useful in preventing AF-related strokes.
Predicting the Dengue Epidemic in Guangzhou, China by Meteorological Parameter Methods
Authors: Chen Jing , Liu Kang-Kang , Xiao Hui , Hu Gang , Xiao Xiang , Lin Yu , Yue Qian , Han Yan , Mao Xiao-Fei , Dong Guang-Hui , Bu Jin 
Published: April 2020

AbstractThis study was aimed to determine dengue season, and further establish a prediction model by meteorological methods. The dengue and meteorological data were collected from Guangdong Meteorological Bureau and Guangdong Provincial Center for Disease Prevention and Control, respectively. We created a sliding accumulated temperature method to accurately calculate the beginning and ending day of dengue season. Probabilistic Forecast model was derived under comprehensive consideration of various weather processes including typhoon, rainstorm, and so on. We found: 1) The dengue fever season enters when effective accumulated temperature of a continuing 45 days (T45) ≥0 °C, and it finishes when effective accumulated temperature of a continuing 6 days (T6) <0 °C. 2) A Probabilistic Forecast Model for dengue epidemic was established with good forecast effects, which were verified by the actual incidence of dengue in Guangzhou. The Probabilistic Forecast Model provides markedly improved forecasting techniques for dengue prediction.
Geo-social gradients in predicted COVID-19 prevalence and severity in Great Britain: results from 2,266,235 users of the COVID-19Symptoms Tracker app
Authors: Bowyer Ruth C E , Varsavsky Thomas , Sudre Carole H. , Murray Benjamin A K , Freidin Maxim B , Yarand Darioush , Ganesh Sajaysurya , Capdevila Joan , Thompson Ellen J , Bakker Elco , Cardoso M. Jorge , Davies Richard , Wolf Jonathan , Spector Tim D , Ourselin Sebastien , Steves Claire J , Menni Cristina 
Published: April 2020

ABSTRACTUnderstanding the geographical distribution of COVID-19 through the general population is key to the provision of adequate healthcare services. Using self-reported data from 2,266,235 unique GB users of theCOVID Symptom Tracker app, we find that COVID-19 prevalence and severity became rapidly distributed across the UK within a month of the WHO declaration of the pandemic, with significant evidence of “urban hot-spots”. We found a geo-social gradient associated with disease severity and prevalence suggesting resources should focus on urban areas and areas of higher deprivation. Our results demonstrate use of self-reported data to inform public health policy and resource allocation.
Estimating population immunity without serological testing
Authors: Lesniewski Andrew 
Published: April 2020

AbstractWe propose an approximate methodology for estimating the overall level of immunity against COVID-19 in a population that has been affected by the recent epidemic. The methodology relies on the currently available mortality data and utilizes the properties of the SIR model. We illustrate the application of the method by estimating the recent levels of immunity in 10 US states with highest case numbers of COVID-19.
A biorefinery concept for the production of fuel ethanol, probiotic yeast and whey protein from a by-product of the cheese industry
Authors: Pendón María Dolores , Madeira José V. , Romanin David E. , Rumbo Martín , Gombert Andreas K. , Garrote Graciela L. 
Published: April 2020

1.AbstractAgroindustrial by-products and residues can be transformed into valuable compounds in biorefineries. Here we present a new concept: production of fuel ethanol, whey protein and probiotic yeast from cheese whey. An initial screening under industrially relevant conditions, involving thirtyKluyveromyces marxianusstrains, was carried out using spot assays to evaluate their capacity to grow on cheese whey or on whey permeate (100 g lactose/L), under aerobic or anaerobic conditions, in the absence or presence of 5% ethanol, at pH 5.8 or pH 2.5. The four best growingK. marxianusstrains were selected and further evaluated in a miniaturized industrial fermentation process using reconstituted whey permeate (100 g lactose/L) with cell recycling (involving sulfuric acid treatment). After five consecutive fermentation cycles, the ethanol yield on sugar reached 90% of the theoretical maximum in the best cases, with 90% cell viability. Cells harvested at this point displayed probiotic properties such as capacity to survive the passage through the gastrointestinal tract and capacity to modulate innate immune response of intestinal epithelium, bothin vitro. Furthermore, the CIDCA 9121 strain was able to protect against histopathological damage in an animal model of acute colitis. Our findings demonstrate thatK. marxianusCIDCA 9121 is capable of efficiently fermenting the lactose present in whey permeate to ethanol and that the remaining yeast biomass has probiotic properties, enabling an integrated process for the obtainment of whey protein, fuel ethanol and probiotics from cheese whey.2.ImportanceCheese whey is the liquid remaining following the precipitation and removal of milk casein during cheese-making. This by-product represents about 85-95% of the milk volume and retains 55% of milk nutrients so it can be exploited as a source of valuable end products. However, at a global level around 50% of cheese whey is wasted, representing an important environmental impact and indicating the need to develop alternative processes to recover value.Kluyveromyces marxianusis capable of fermenting lactose, generally regarded as safe, and has been explored separately as an ethanol producer and as a viable bioactive microorganism. The significance of our research is to establish the proof of concept that a biorefinery for fuel ethanol production using whey andK. marxianuscan also be exploited to obtain viable probiotic biomass, conferring an added value to the process and providing an alternative to reduce environmental impact.
Phytochrome mediated responses inAgrobacterium fabrum: growth, swimming, plant infection and interbacterial competition
Authors: Xue Peng , Bai Yingnan , Rottwinkel Gregor , Averbukh Elizaveta , Ma Yuanyuan , Roeder Thomas , Scheerer Patrick , Krauß Norbert , Lamparter Tilman 
Published: April 2020

AbstractThe soil bacteriumAgrobacterium fabrumC58 infects plants by a unique DNA transfer mechanism.A. fabrumhas two phytochrome photoreceptors, Agp1 and Agp2. We found that DNA transfer into plants byA. fabrumis down regulated by light and that phytochrome knockout mutants have diminished DNA transfer rates. The regulation pattern matches with that of bacterial conjugation reported earlier. Growth, swimming and interbacterial competition were also affected in phytochrome knockout mutants, although these effects were often not affected by light. We can thus distinguish between light-regulated and light-independent phytochrome responses. In microarray studies, transcription of only 4 genes was affected by light, indicating that most light responses are regulated post-transcriptionally. In a mass spectrometery-based proteomic study, 24 proteins were different between light and dark grown bacteria, whereas 382 proteins differed between wild type and phytochrome knockout mutants, pointing again to light-dependent and light-independent roles of Agp1 and Agp2.
Pancreatic beta-cell specific deletion of VPS41 causes diabetes due to defects in insulin secretion
Authors: Burns Christian H. , Yau Belinda , Rodriguez Anjelica , Triplett Jenna , Maslar Drew , An You Sun , van der Welle Reini E.N. , Kossina Ross G. , Fisher Max R. , Strout Gregory W. , Bayguinov Peter O. , Veenendaal Tineke , Chitayat David , Fitzpatrick James A.J. , Klumperman Judith , Kebede Melkam A. , Asensio Cedric S. 
Published: April 2020

AbstractInsulin secretory granules (SGs) mediate the regulated secretion of insulin, which is essential for glucose homeostasis. The basic machinery responsible for this regulated exocytosis consists of specific proteins present both at the plasma membrane and on insulin SGs. The protein composition of insulin SGs thus dictates their release properties, yet the mechanisms controlling insulin SG formation, which determines this molecular composition, remain poorly understood. VPS41, a component of the endo-lysosomal tethering HOPS complex, was recently identified as a cytosolic factor involved in the formation of neuroendocrine and neuronal granules. We now find that VPS41 is required for insulin SG biogenesis and regulated insulin secretion. Loss of VPS41 in pancreatic β-cells leads to a reduction in insulin SG number, changes in their transmembrane protein composition, and defects in granule regulated exocytosis. Exploring a human point mutation, identified in patients with neurological but no endocrine defects, we show that the effect on SG formation is independent of HOPS complex formation. Finally, we report that mice with a deletion of VPS41 specifically in β-cells develop diabetes due to severe depletion of insulin SG content and a defect in insulin secretion. In sum, our data demonstrate that VPS41 contributes to glucose homeostasis and metabolism.
State-selective Modulation of Heterotrimeric Gαs Signaling with Macrocyclic Peptides
Authors: Dai Shizhong A. , Hu Qi , Gao Rong , Peacock Hayden , Blythe Emily E. , Zhang Ziyang , von Zastrow Mark , Suga Hiroaki , Shokat Kevan M. 
Published: April 2020

SUMMARYThe G protein-coupled receptor (GPCR) cascade leading to production of the second messenger cAMP is replete with pharmacologically targetable receptors and enzymes with the exception of the Gα subunit, Gαs. GTPases remain largely undruggable given the difficulty of displacing high-affinity guanine nucleotides and the lack of other drug binding sites. We explored a chemical library of 1012cyclic peptides in order to expand the chemical search for inhibitors of this enzyme class. We identified two macrocyclic peptides, GN13 and GD20, that antagonize the active and inactive states of Gαs, respectively. Both macrocyclic peptides fine-tune Gαs activity with high nucleotide-binding-state selectivity and G protein class-specificity. Co-crystal structures reveal that GN13 and GD20 distinguish the conformational differences within the switch II/α3 pocket and block effector interactions. The Gαs inhibitors showed strong activity in cellular contexts through binding to crystallographically defined pockets. The discovery of cyclic peptide inhibitors targeting Gαs provides a path for further development of state-dependent GTPase inhibitors.
Heterologous production of 1-tuberculosinyladenosine inMycobacterium kansasiimodels pathoevolution towards the transcellular lifestyle ofMycobacterium tuberculosis
Authors: Ghanem Marwan , Dubé Jean-Yves , Wang Joyce , McIntosh Fiona , Houle Daniel , Domenech Pilar , Reed Michael B. , Raman Sahadevan , Buter Jeffrey , Minnaard Adriaan J. , Moody D. Branch , Behr Marcel A. 
Published: April 2020

ABSTRACTMycobacterium kansasiiis an environmental non-tuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to theM. tuberculosiscomplex. UsingM. kansasiias a proxy for theM. kansasii-M. tuberculosis-common ancestor, we asked whether introducing theM. tuberculosis-specific gene pairRv3377c-Rv3378cintoM. kansasiiaffects the course of experimental infection. Expression of these genes resulted in the production of an adenosine-linked lipid species, known as 1-tuberculosinyladenosine (1-TbAd), but did not alter growthin vitrounder standard conditions. Production of 1-TbAd enhanced growth ofM. kansasiiunder acidic conditions through a bacterial cell-intrinsic mechanism independent of controlling pH in the bulk extracellular and intracellular spaces. Production of 1-TbAd led to greater burden ofM. kansasiiin the lung of C57Bl/6 mice during the first 24 hours after infection andex vivoinfections of alveolar macrophages recapitulated this phenotype within the same time frame. However, in long-term infections, production of 1-TbAd resulted in impaired bacterial survival in both C57Bl/6 mice andCcr2-/-mice. We have demonstrated thatM. kansasiiis a valid surrogate ofM. tuberculosisto study virulence factors acquired by the latter organism, yet shown the challenge inherent to studying the complex evolution of mycobacterial pathogenicity with isolated gene complementation.IMPORTANCEThis work sheds light on the role of the lipid 1-tuberculosinyladenosine in the evolution of an environmental ancestor toM. tuberculosis. On a larger scale, it reinforces the importance of horizontal gene transfer in bacterial evolution and examines novel models and methods to provide a better understanding of the subtle effects of individualM. tuberculosis-specific virulence factors in infection settings that are relevant to the pathogen.
Phytotoxin synthesis genes and type III effector genes ofPseudomonas syringaepv.actinidiaebiovar 6 are regulated by culture conditions
Authors: Hirose Karin , Ishiga Yasuhiro , Fujikawa Takashi 
Published: April 2020

AbstractThe kiwifruit bacterial canker (Pseudomonas syringaepv.actinidiae; Psa) causes severe damage to kiwifruit production worldwide. Psa biovar 6 (Psa6), which was isolated in Japan in 2015, produces two types of phytotoxins: coronatine and phaseolotoxin. To date, no other phytopathogenic bacteria are known to produce two phytotoxins. To elucidate the unique virulence of Psa6, we performed transcriptomic analysis of phytotoxin synthesis genes and type III effector genes inin vitrocultivation using various media. The genes related to phytotoxin synthesis and effectors of Psa6 were strictly regulated in the coronatine-inducing mediums (HS and HSC); 14 of 23 effector genes and ahrpLsigma factor gene were induced at 3 h after transferring to the media (early-inducible genes), and phytotoxin synthesis genes such asargDof phaseolotoxin andcflof coronatine were induced at 6 and 12 h after transferring to the media (late-inducible genes). In contrast, induction of these genes was not observed in thehrp-inducing medium. Next, to examine whether the changes in gene expression in different media is specific to Psa6, we investigated gene expression in other related bacteria. For Psa biovar 1 (Psa1), biovar 3 (Psa3), andP. s.pv.glycinea(Psg), no clear trends were observed in expression behavior across various culture media and incubation times. Therefore, Psa6 seems to exert its virulence efficiently by using two phytotoxins and effectors according to environmental changes. This is not seen in other biovars and pathovars, so it is thought that Psa6 has acquired its own balance of virulence.
Gain of gene regulatory network interconnectivity at the origin of vertebrates
Authors: Gil-Gálvez Alejandro , Jiménez-Gancedo Sandra , Acemel Rafael D. , Bertrand Stephanie , Schubert Michael , Escrivá Héctor , Tena Juan J. , Gómez-Skarmeta José Luis 
Published: April 2020

AbstractSignaling pathways control a large number of gene regulatory networks (GRNs) during animal development, acting as major tools for body plan formation1. Remarkably, in contrast to the large number of transcription factors present in animal genomes, only a few of these pathways operate during development2. Moreover, most of them are largely conserved along metazoan evolution3. How evolution has generated a vast diversity of animal morphologies with such a limited number of tools is still largely unknown. Here we show that gain of interconnectivity between signaling pathways, and the GRNs they control, may have played a critical contribution to the origin of vertebrates. We perturbed the retinoic acid, Wnt, FGF and Nodal signaling pathways during gastrulation in amphioxus and zebrafish and comparatively examined its effects in gene expression and cis-regulatory elements (CREs). We found that multiple developmental genes gain response to these pathways through novel CREs in the vertebrate lineage. Moreover, in contrast to amphioxus, many of these CREs are highly interconnected and respond to multiple pathways in zebrafish. Furthermore, we found that vertebrate-specific cell types are more enriched in highly interconnected genes than those tissues with more ancestral origin. Thus, the increase of CREs in vertebrates integrating inputs from different signaling pathways probably contributed to gene expression complexity and the formation of new cell types and morphological novelties in this lineage.
Polycationic gold nanorods as multipurposein vitromicrotubule markers
Authors: Wedler Viktoria , Strauß Fabian , Sudhakar Swathi , Hermsdorf Gero Lutz , Stierhof York-Dieter , Schäffer Erik 
Published: April 2020

AbstractGold nanoparticles are intriguing because of their unique size- and shape-dependent chemical, electronic and optical properties. Various microscopy and biomedical applications are based on the particles’ biocompatibility, surface functionalizability, light absorption, and plasmon resonances. Gold nanorods (AuNRs) are particularly promising for various sensor applications due to their tip-enhanced plasmonic fields. For biomolecule attachment, AuNRs are often stabilized with amphiphilic molecules and functionalized with antibodies or biotin-binding proteins. However, by their intrinsic size such molecules block the most sensitive near-field region of the AuNRs. Here, we used short cationic thiols to covalently functionalize the gold surface. We show that the functionalization layer is thin and that these polycationic AuNRs bindin vitroto negatively charged microtubule filaments. Furthermore, we can plasmonically stimulate light emission from the AuNRs and, therefore, use them as bleach- and blinkfree microtubule markers. We confirmed colocalization by transmission electron microscopy or the combination of interference reflection and single-molecule fluorescence microscopy of fluorescently-labeled or plasmonic photoluminescent versions of the AuNRs. We expect that polycationic AuNRs may be applicable toin vivosystems and other negatively charged molecules like DNA. In the long-term, microtubule-bound AuNRs can be used as ultrasensitive single-molecule sensors for molecular machines that interact with microtubules.
Heritability jointly Explained by Host Genotype and Microbiome:Will Improve Traits Prediction?
Authors: Awany Denis , Chimusa Emile R. 
Published: April 2020

AbstractAs we observe the 70thanniversary of the publication by Robertson that formalized the notion of ‘heritability’, geneticists remain puzzled by the problem of missing/hidden heritability, where heritability estimates from genome-wide association studies (GWAS) fall short of that from twin-based studies. Many possible explanations have been offered for this discrepancy, including existence of genetic variants poorly captured by existing arrays, dominance, epistasis, and unaccounted-for environmental factors; albeit these remain controversial. We believe a substantial part of this problem could be solved or better understood by incorporating the host’s microbiota information in the GWAS model for heritability estimation; ultimately also increasing human traits prediction for clinical utility. This is because, despite empirical observations such as (i) the intimate role of the microbiome in many complex human phenotypes, (ii) the overlap between genetic variants associated with both microbiome attributes and complex diseases, and (iii) the existence of heritable bacterial taxa, current GWAS models for heritability estimate do not take into account the contributory role of the microbiome. Furthermore, heritability estimate from twin-based studies does not discern microbiome component of the observed total phenotypic variance. Here, we summarize the concept of heritability in GWAS and microbiome-wide association studies (MWAS), focusing on its estimation, from a statistical genetics perspective. We then discuss a possible method to incorporate the microbiome in the estimation of heritability in host GWAS.