bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting mortality, duration of treatment, pulmonary embolism and required ceiling of ventilatory support for COVID-19 inpatients: A Machine-Learning Approach
Authors: Vepa Abhinav , Saleem Amer , Rakhshan Kambiz , Omar Amr , Dharmaraj Diana , Sami Junaid , Parekh Shital , Ibrahim Mohamed , Raza Mohammed , Kapila Poonam , Chakrabarti Prithwiraj , Sedighi Tabassom , Chatrabgoun Omid , Daneshkhah Alireza 
Published: February 2021

AbstractIntroductionWithin the UK, COVID-19 has contributed towards over 103,000 deaths. Multiple risk factors for COVID-19 have been identified including various demographics, co-morbidities, biochemical parameters, and physical assessment findings. However, using this vast data to improve clinical care has proven challenging.Aimsto develop a reliable, multivariable predictive model for COVID-19 in-patient outcomes, to aid risk-stratification and earlier clinical decision-making.MethodsAnonymized data regarding 44 independent predictor variables of 355 adults diagnosed with COVID-19, at a UK hospital, was manually extracted from electronic patient records for retrospective, case-controlled analysis. Primary outcomes included inpatient mortality, level of ventilatory support and oxygen therapy required, and duration of inpatient treatment. Secondary pulmonary embolism was the only secondary outcome. After balancing data, key variables were feature selected for each outcome using random forests. Predictive models were created using Bayesian Networks, and cross-validated.ResultsOur multivariable models were able to predict, using feature selected risk factors, the probability of inpatient mortality (F1 score 83.7%, PPV 82%, NPV 67.9%); level of ventilatory support required (F1 score varies from 55.8% “High-flow Oxygen level” to 71.5% “ITU-Admission level”); duration of inpatient treatment (varies from 46.7% for “≥ 2 days but < 3 days” to 69.8% “≤ 1 day”); and risk of pulmonary embolism sequelae (F1 score 85.8%, PPV of 83.7%, and NPV of 80.9%).ConclusionOverall, our findings demonstrate reliable, multivariable predictive models for 4 outcomes, that utilize readily available clinical information for COVID-19 adult inpatients. Further research is required to externally validate our models and demonstrate their utility as clinical decision-making tools.HighlightsUsing COVID-19 risk-factor data to assist clinical decision making is a challengeAnonymous data from 355 COVID-19 inpatients was collected & balancedKey independent variables were feature selected for 4 different outcomesAccurate, multi-variable predictive models were computed, using Bayesian NetworksFuture research should externally validate our models & demonstrate clinical utility
Behavioral control by depolarized and hyperpolarized states of an integrating neuron by
Authors: Sordillo Aylesse , Bargmann Cornelia I. 
Published: February 2021

ABSTRACTCoordinated transitions between mutually exclusive motor states are central to behavioral decisions. During locomotion, the nematodeCaenorhabditis elegansspontaneously cycles between forward runs, reversals, and turns with complex but predictable dynamics. Here we provide insight into these dynamics by demonstrating how RIM interneurons, which are active during reversals, act in two modes to stabilize both forward runs and reversals. By systematically quantifying the roles of RIM outputs during spontaneous behavior, we show that RIM lengthens reversals when depolarized through glutamate and tyramine neurotransmitters and lengthens forward runs when hyperpolarized through its gap junctions. RIM is not merely silent upon hyperpolarization: RIM gap junctions actively reinforce a hyperpolarized state of the reversal circuit. Additionally, the combined outputs of chemical synapses and gap junctions from RIM regulate forward-to-reversal transitions. Our results indicate that multiple classes of RIM synapses create behavioral inertia during spontaneous locomotion.
Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes
Authors: Shulgach Jonathan A. , Beam Dylan W. , Nanivadekar Ameya C. , Miller Derek M. , Fulton Stephanie , Sciullo Michael , Ogren John , Wong Liane , McLaughlin Bryan , Yates Bill J. , Horn Charles C. , Fisher Lee E. 
Published: February 2021

AbstractDysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N=3) or ventral (N=3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that is was possible to selectively activate subpopulations of vagal afferents using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e. Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.
An mRNA expression-based signature for oncogene-induced replication-stress
Authors: Llobet Sergi Guerrero , Bhattacharya Arkajyoti , Everts Marieke , van der Vegt Bert , Fehrmann Rudolf S.N. , van Vugt Marcel A.T.M. 
Published: February 2021

ABSTRACTBackgroundOncogene-induced replication stress characterizes many aggressive cancers, including triple-negative breast cancer (TNBC). Several drugs are being developed that target replication stress, although it is unclear how tumors with high levels of replication stress can be identified. We aimed to develop a gene expression signature of oncogene-induced replication stress.MethodsTNBC and non-transformed RPE1-TP53wtand RPE1-TP53mutcell lines were engineered to overexpress the oncogenesCDC25A,CCNE1orMYC. DNA fiber analysis was used to measure replication kinetics. Analysis of RNA sequencing data of cell lines and patient-derived tumor samples (TCGA n=10,592) was used to identify differential gene expression. Immunohistochemical validation was conducted on breast cancer samples (n=330).ResultsRNA sequencing revealed 52 commonly upregulated genes after induction ofCDC25A,CCNE1orMYCin our cell line panel. Integration with gene expression data of TGCA samples with amplification of replication stress-inducing oncogenes (CDC25A,CCNE1,MYC,CCND1,MYB,MOS,KRAS,ERBB2, andE2F1), yielded a six-gene signature of oncogene-induced replication stress (NAT10,DDX27,ZNF48,C8ORF33,MOCS3,andMPP6). Expression of NAT10 in breast cancer samples was correlated with phospho-RPA (R=0.451, p=1.82×10−20) and γH2AX (R=0.304, p=2.95×10−9). Applying the oncogene-induced replication stress signature to patient samples (TCGA n=8,862 and GEO n=13,912) defined the replication stress landscape across 27 tumor subtypes, and identified diffuse large B cell lymphoma, ovarian cancer, TNBC and colorectal carcinoma as cancer subtypes with high levels of oncogene-induced replication stress.ConclusionWe developed a gene expression signature of oncogene-induced replication stress, which may facilitate patient selection for agents that target replication stress.
Establishment of a human three-dimensional chip-based chondro-synovial co-culture joint model for reciprocal cross-talk studies in arthritis research
Authors: Rothbauer Mario , Byrne Ruth A. , Schobesberger Silvia , Calvo Isabel Olmos , Fischer Anita , Reihs Eva I. , Spitz Sarah , Bachmann Barbara , Sevelda Florian , Holinka Johannes , Holnthoner Wolfgang , Redl Heinz , Tögel Stefan , Windhager Reinhard , Kiener Hans P. , Ertl Peter 
Published: February 2021

AbstractRheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane, which is the joint capsule’s inner layer, is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA’s synovial-chondral axis has yet not been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue co-culture model that simulates the reciprocal cross-talk between individual synovial and chondral organoids. We now demonstrate that chondral organoids, when co-cultivated with synovial organoids, induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross-talk in the modelling of arthritic diseases.
Relative and quantitative rhizosphere microbiome profiling result in distinct abundance patterns
Authors: Azarbad Hamed , Tremblay Julien , Bainard Luke D. , Yergeau Etienne 
Published: February 2021

AbstractNext-generation sequencing is recognized as one of the most popular and cost-effective way of characterizing microbiome in multiple samples. However, most of the currently available amplicon sequencing approaches are inherently limited, as they are often presented based on the relative abundance of microbial taxa, which may not fully represent actual microbiome profiles. Here, we combined amplicon sequencing (16S rRNA gene for bacteria and ITS region for fungi) with real-time quantitative PCR (qPCR) to characterize the rhizosphere microbiome of wheat. We show that the increase in relative abundance of major microbial phyla does not necessarily result in an increase in abundance. One striking observation when comparing relative and quantitative abundances was a substantial increase in the abundance of almost all phyla associated with the rhizosphere of plants grown in soil with no history of water stress as compared with the rhizosphere of plants growing in soil with a history of water stress, which was in contradiction with the trends observed in the relative abundance data. Our results suggest that the estimated absolute abundance approach gives a different perspective than the relative abundance approach, providing complementary information that helps to better understand the rhizosphere microbiome.
Aedes albopictusbionomics in Procida Island, a promising Mediterranean site for the assessment of innovative and community-based integrated pest management methods
Authors: Caputo B. , Langella G. , Petrella V. , Virgillito C. , Manica M. , Filipponi F. , Varone M. , Primo P. , Puggioli A. , Bellini R. , D’Antonio C. , Iesu L. , Tullo L. , Rizzo C. , Longobardi A. , Sollazzo G. , Perrotta M. M. , Fabozzi M. , Palmieri F. , Saccone G , Rosà R. , della Torre A. , Salvemini M. 
Published: February 2021

AbstractThe colonization of Mediterranean Europe and of other temperate regions byAedes albopictuscreated in the last decades an unprecedented nuisance problem in highly infested areas, as well as a new public health threat due to the species competence to transmit exotic arboviruses, such as dengue, chikungunya and zika. The Sterile Insect Technique (SIT) and the Incompatible Insect Technique (IIT) are insecticide-free mosquito-control methods relying on mass release of irradiated/manipulated males which are believed to have a potential in complementing existing and only partially effective control tools. Testing and implementing these approaches are challenging and selection of study sites is an instrumental and crucial step. We carried out a 4-year study in Procida Island (Gulf of Naples, Italy) in strict collaboration with local administrators and citizens to estimate: i) the temporal dynamics, spatial distribution, and population size ofAe. albopictus; and ii) the dispersal and survival of irradiated males. Overall, results provide insights on the bionomics of the mosquito in Southern Europe and draw attention to Procida Island as an ideal site to test innovative control programs againstAe. albopictuswhich may be used in other Mediterranean and temperate areas.”
Complex polyploid and hybrid species in an apomictic and sexual tropical forage grass group: genomic composition and evolution inUrochloa(Brachiaria) species
Authors: Tomaszewska Paulina , Vorontsova Maria S. , Renvoize Stephen A. , Ficinski Sarah Z. , Tohme Joseph , Schwarzacher Trude , Castiblanco Valheria , de Vega José J. , Mitchell Rowan A. C. , Heslop-Harrison J. S. (Pat) 
Published: February 2021

AbstractBackground and AimsDiploid and polyploidUrochloa(includingBrachiaria,PanicumandMegathyrsusspecies) C4tropical forage grasses originating from Africa and now planted worldwide are important for food security and the environment, often being planted in marginal lands. We aimed to characterize the nature of their genomes, the repetitive DNA, and the genome composition of polyploids, leading to a model of the evolutionary pathways within the group including many apomictic species.MethodsSome 362 forage grass accessions from international germplasm collections were studied, and ploidy determined using an optimized flow cytometry method. Whole-genome survey sequencing and molecular cytogenetic analysis within situhybridization to chromosomes were used to identify chromosomes and genomes inUrochloaaccessions belonging to the different agamic complexes.Key ResultsGenome structures are complex and variable, with multiple ploidies and genome compositions within the species, and no clear geographical patterns. Sequence analysis of nine diploid and polyploid accessions enabled identification of abundant genome-specific repetitive DNA motifs.In situhybridization with a combination of repetitive DNA and genomic DNA probes, identified evolutionary divergence and allowed us to discriminate the different genomes present in polyploids.ConclusionsWe suggest a new coherent nomenclature for the genomes present. We develop a model of evolution at the whole-genome level in diploid and polyploid accessions showing processes of grass evolution. We support the retention of narrow species concepts forU. brizantha, U. decumbens, andU. ruziziensis. The results and model will be valuable in making rational choices of parents for new hybrids, assist in use of the germplasm for breeding and selection ofUrochloawith improved sustainability and agronomic potential, and will assist in measuring and conserving biodiversity in grasslands.
Efficiency Improvements and Discovery of New Substrates for a SARS-CoV-2 Main Protease FRET Assay
Authors: Dražić Tonko , Kühl Nikos , Leuthold Mila M. , Behnam Mira A. M. , Klein Christian D. 
Published: February 2021

ABSTRACTThe COVID-19 pandemic, caused by the SARS-CoV-2 virus, has a huge impact on the world. Although several vaccines have recently reached the market, the development of specific antiviral drugs against SARS-CoV-2 is an important additional strategy in fighting the pandemic. One of the most promising pharmacological targets is the viral main protease (Mpro). Here, we present an optimized biochemical assay procedure for SARS-CoV-2 Mpro. We have comprehensively investigated the influence of different buffer components and conditions on the assay performance, and characterized six FRET substrates with a 2-Abz/Tyr(3-NO2) FRET pair. The substrates 2-AbzSAVLQSGTyr(3-NO2)R-OH, a truncated version of the established DABCYL/EDANS FRET substrate, and a new substrate 2-AbzVVTLQSGTyr(3-NO2)R-OH are promising candidates for screening and inhibitor characterization. In the latter substrate, the incorporation of Val at the position P5 improved the catalytic efficacy. Based on the obtained results, we present here a reproducible, reliable assay protocol using highly affordable buffer components.
SMAD4 governs a feedforward regulation of the TGF-β-effects in CD8 T cells that contributes to preventing chronic intestinal inflammation
Authors: Igalouzene Ramdane , Hernandez-Vargas Hector , Benech Nicolas , Bauché David , Barrachina Célia , Dubois Emeric , Marie Julien C. , Soudja Saïdi M’Homa 
Published: February 2021

AbstractSMAD4, a key mediator of TGF-β signaling, plays a crucial role in T cells to prevent chronic gut inflammation. However, the molecular mechanisms underlying this control remain elusive. Using different genetic and epigenetic approaches, we unexpectedly reveal that SMAD4 in CD8 T cells prevents chronic intestinal inflammation by a feedforward mechanism that is TGF-β-independent. Prior to any TGF-β-receptor engagement, SMAD4 acts as an active and basal repressor of epigenetic, transcriptional and functional TGF-β imprinting in CD8 T cells. Thus, in sharp opposition to total TGF-β signaling deletion, SMAD4 deletion impairs naïve CD8 T cell effector predisposition but promotes CD8 T cell accumulation and epithelial retention by promoting their response to IL-7 and their expression of integrins such asItgae. Besides, SMAD4 deletion unleashes the induction of a wide range of TGF-β-signaling-repressors such asSmad7, Ski, Skil, andSmurf2and hampers TGF-β-mediated CD8 T cell immunosuppression. Mechanistically, prior to any TGF-β signal, SMAD4 binds to the loci of several TGF-β-target genes, and by regulating histone acetylation, represses their expression. The massive gut epithelial colonization, associated with their escape from the immunoregulatory TGF-β effects overtakes their poor effector preconditioning and elicits microbiota-driven chronic epithelial CD8 T cell activation. Hence, in an anticipatory manner, independently of TGF-β, SMAD4 governs a feedforward regulation of TGF-β effects in CD8 T cells, preventing chronic intestinal inflammation.
Viperin inhibits cholesterol biosynthesis and interacts with enzymes in the cholesterol biosynthetic pathway
Authors: Grunkemeyer Timothy J. , Ghosh Soumi , Patel Ayesha M. , Sajja Keerthi , Windak James , Basrur Venkatesha , Kim Youngsoo , Nesvizhskii Alexey I. , Kennedy Robert T. , Marsh E. Neil G. 
Published: February 2021

AbstractMany enveloped viruses bud from cholesterol-rich lipid rafts on the cell membrane. Depleting cellular cholesterol impedes this process and results in viral particles with reduced viability. Viperin (virus inhibitory protein endoplasmic reticulum-associated, interferon-induced) is an ER membrane-associated enzyme that when expressed in response to viral infections exerts broad-ranging antiviral effects, including inhibiting the budding of some enveloped viruses. Here we have investigated the effect of viperin expression on cholesterol biosynthesis. We found that viperin expression reduces cholesterol levels by 20 – 30 % in HEK293T cells. A proteomic screen of the viperin interactome identified several cholesterol biosynthetic enzymes among the top hits. The two most highly enriched proteins were lanosterol synthase and squalene monooxygenase, enzymes that catalyze key steps establishing the sterol carbon skeleton. Co-immunoprecipitation experiments established that viperin, lanosterol synthase and squalene monooxygenase form a complex at the ER membrane. Co-expression of viperin was found to significantly inhibit the specific activity of lanosterol synthase in HEK293T cell lysates. Co-expression of viperin had no effect on the specific activity of squalene monooxygenase, but reduced its expression levels in the cells by approximately 30 %. Despite these inhibitory effects, co-expression of either LS or SM failed to reverse the viperin-induced depletion of cellular cholesterol levels in HEK293T cells. Our results establish a clear link between the down-regulation of cholesterol biosynthesis and viperin, although at this point the effect cannot be unambiguously attributed interactions between viperin and a specific biosynthetic enzyme.
Squidpy: a scalable framework for spatial single cell analysis
Authors: Palla Giovanni , Spitzer Hannah , Klein Michal , Fischer David , Schaar Anna Christina , Kuemmerle Louis Benedikt , Rybakov Sergei , Ibarra Ignacio L. , Holmberg Olle , Virshup Isaac , Lotfollahi Mohammad , Richter Sabrina , Theis Fabian J. 
Published: February 2021

AbstractSpatial omics data are advancing the study of tissue organization and cellular communication at an unprecedented scale. Here, we present Squidpy, a Python framework that brings together tools from omics and image analysis to enable scalable description of spatial molecular data, such as transcriptome or multivariate proteins. Squidpy provides both infrastructure and numerous analysis methods that allow to efficiently store, manipulate and interactively visualize spatial omics data.
mRNA codon optimization on quantum computers
Authors: Fox Dillion M. , Branson Kim M. , Walker Ross C. 
Published: February 2021

AbstractReverse translation of polypeptide sequences to expressible mRNA constructs is a NP-hard combinatorial optimization problem. Each amino acid in the protein sequence can be represented by as many as six codons, and the process of selecting the combination that maximizes probability of expression is termed codon optimization. This work investigates the potential impact of leveraging quantum computing technology for codon optimization. An adiabatic quantum computer (AQC) is compared to a standard genetic algorithm (GA) programmed with the same objective function. The AQC is found to be competitive in identifying optimal solutions and future generations of AQCs may be able to outperform classical GAs. The utility of gate-based systems is also evaluated using a simulator resulting in the finding that while current generations of devices lack the hardware requirements, in terms of both qubit count and connectivity, to solve realistic problems, future generation devices may be highly efficient.