bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring integration and influence among health professionals. A social network approach
Authors: Aguirre Nelson , Carswell Peter , Keneally Tim 
Published: April 2020

AbstractPrograms to manage long term conditions in developed countries seek greater integration and communication between health professionals to improve health outcomes. But more empirical evidence is needed to measure integration and influence for health those who are involved in these programs. This paper analyses the way in which health professionals interact at the primary and secondary care interface, based on integrated care design in a program of chronic care in New Zealand. The frequency, quality and perceived value of the interactions between general practitioners, practices nurses, medical specialists and specialist nurses are used as explanatory variables in graphical models which take a social network analysis approach. The paper shows the configuration of the network between health professionals in an integrated care context and explains the academic and policy implication of the findings.
Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens
Authors: Vashi Yoya , Jagrit Vipin , Kumar Sachin 
Published: April 2020

AbstractThe 2019 novel severe respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide. The present study followed computational approaches to identify B- and T-cell epitopes for spike glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified twenty-four peptide stretches on the SARS-CoV-2 spike protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface. Out of which twenty are surface exposed and predicted to have reasonable epitope binding efficiency. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics.
Neuronal Modeling of Alternating Hemiplegia of Childhood Reveals Transcriptional Compensation and Replicates a Trigger-Induced Phenotype
Authors: Snow John P. , Westlake Grant , Klofas Lindsay K. , Jeon Soyoun , Armstrong Laura C. , Swoboda Kathryn J. , George Alfred L. , Ess Kevin C. 
Published: April 2020

ABSTRACTAlternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disease caused by heterozygous de novo missense mutations in the ATP1A3 gene that encodes the neuronal specific α3 subunit of the Na,K-ATPase (NKA) pump. Mechanisms underlying patient episodes including environmental triggers remain poorly understood, and there are no empirically proven treatments for AHC. In this study, we generated patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls for the E815K ATP1A3 mutation that causes the most phenotypically severe form of AHC. Using an in vitro iPSC-derived cortical neuron disease model, we found elevated levels of ATP1A3 mRNA in AHC lines compared to controls, without significant perturbations in protein expression. Microelectrode array analyses demonstrated that in cortical neuronal cultures, ATP1A3+/E815K iPSC-derived neurons displayed a non-significant trend toward less overall activity than neurons differentiated from isogenic mutation-corrected and unrelated control cell lines. However, induction of cellular stress by elevated temperature revealed a hyperactivity phenotype following heat stress in ATP1A3+/E815K lines compared to control lines. Treatment with flunarizine, a drug commonly used to prevent AHC episodes, did not impact this stress-triggered phenotype. These findings support the use of iPSC-derived neuronal cultures for studying complex neurodevelopmental conditions such as AHC and provide a potential route toward future therapeutic screening and mechanistic discovery in a human disease model.
20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor
Authors: Lafont René , Raynal Sophie , Serova Maria , Didry-Barca Blaise , Guibout Louis , Latil Mathilde , Dilda Pierre J. , Dioh Waly , Veillet Stanislas 
Published: April 2020

ABSTRACT20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysone receptors (EcRs) and at least one membrane GPCR receptor (DopEcR) and displays numerous pharmacological effects in mammals. However, its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ERβ receptor. The goal of our study was to better understand 20E mechanism of action.A mouse myoblast cell line (C2C12) and the gene expression of myostatin (a negative regulator of muscle growth) was used as a reporter system of anabolic activity. Experiments using protein-bound 20E established the involvement of a membrane receptor. 20E-like effects were also observed with Angiotensin-(1-7), the endogenous ligand of Mas. Additionally, the effect on myostatin gene expression was abolished by Mas receptor knock-down using small interfering RNA (siRNA) or pharmacological inhibitors.17β-Estradiol (E2) also inhibited myostatin gene expression, but protein-bound E2 was inactive, and E2 activity was not abolished by angiotensin-(1-7) antagonists. A mechanism involving cooperation between Mas receptor and a membrane-bound palmitoylated estrogen receptor is proposed.The possibility to activate the Mas receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and indeed this mechanism may explain the close similarity between angiotensin-(1-7) and 20E effects. Our findings open a lot of possible therapeutic developments by stimulating the protective arm of the renin-angiotensin-aldosterone system (RAAS) with 20E.
A minimal and adaptive prediction strategy for critical resource planning in a pandemic
Authors: Prakash Meher K. , Kaushal Shaurya , Bhattacharya Soumyadeep , Chandran Akshay , Kumar Aloke , Ansumali Santosh 
Published: April 2020

AbstractCurrent epidemiological models can in principle model the temporal evolution of a pandemic. However, any such model will rely on parameters that are unknown, which in practice are estimated using stochastic and poorly measured quantities. As a result, an early prediction of the long-term evolution of a pandemic will quickly lose relevance, while a late model will be too late to be useful for disaster management. Unless a model is designed to be adaptive, it is bound either to lose relevance over time, or lose trust and thus not have a second-chance for retraining. We propose a strategy for estimating the number of infections and the number of deaths, that does away with time-series modeling, and instead makes use of a “phase portrait approach.” We demonstrate that, with this approach, there is a universality to the evolution of the disease across countries, that can then be used to make reliable predictions. These same models can also be used to plan the requirements for critical resources during the pandemic. The approach is designed for simplicity of interpretation, and adaptivity over time. Using our model, we predict the number of infections and deaths in Italy and New York State, based on an adaptive algorithm which uses early available data, and show that our predictions closely match the actual outcomes. We also carry out a similar exercise for India, where in addition to projecting the number of infections and deaths, we also project the expected range of critical resource requirements for hospitalizations in a location.
Extrafascial transfissural approach with finger fracture technique approach for liver resection.Old is still gold?
Authors: Vasavada Bhavin B , Patel Hardik 
Published: April 2020

AbstractBackgroundWe evaluated our protocol of extrafascial transfissural approach for liver resection with intrafascial approach that we use in case of donor hepatectomy.Material and MethodWe use extrafascial transfissural approach with finger fracture technique for liver resections and inftrafascial approach with clamp crush technique in case of donor hepatectomy. Major hepatectomy defined as resection of 2 or more adjacent segments.We compared these two techniques with regard to blood loss, operative time, morbidity and mortality.We also evaluated over all factors responsible for 90 days mortality.statistical analysis was done using SPSS version 23.(IBM).Categorical factors were evaluated using chi square test and numerical factors were analyzed using Mann Whitney U test. Multivariate analysis was done using logisitic regression method. Ethical approval for our clinical study was obtained by human research COA number SBI 3246.ResultsWe evaluated 26 liver resections done in last three years. 19 liver resections were done using extrafascial transfissural approach for various liver tumors and 7 living donor hepatectomies were done using itrafascial technique with clamp crush methods. Mean age of patients was 50.73 years.16 patients were males and 10 were females. Mean blood loss was 273.9 ml and mean operative duration was 184.7 minutes. 22 were major resections, 4 were minor liver resections. All minor liver resections were in transfissural approach however there was no statistical significant difference between them. Being live liver doners patients in intrafacial group they were younger than extrafascial transfissural group. (p=0.01). There was no statistical significant difference in blood loss, blood products requirements, morbidity, in hospital and 90 days mortality in both the groups. However extrafascial transfissural with finger fracture technique was associated with significant less operative time. (168.13 minutes vs 222.86 minutes) (p=0.006). 90 days mortality was associated with higher ASA grade (0.018) and blood loss (0.008). However in multivariate analysis no factor indepedently predicted mortality.ConclusionExtrafascial transfissural approach significantly reduces operative time, without affecting morbidity and mortality in liver resection.
Litter decomposition rates of biocrust-forming lichens are similar to that of vascular plants and are affected by warming in a semiarid grassland
Authors: Berdugo Miguel , Mendoza-Aguilar Dinorah O. , Rey Ana , Ochoa Victoria , Gozalo Beatriz , García-Huss Laura , Maestre Fernando T. 
Published: April 2020

AbstractDespite the high relevance of communities dominated by lichens, mosses and cyanobacteria living on the soil surface (biocrusts) for ecosystem functioning in drylands worldwide, no study to date has investigated the decomposition of biocrust-forming lichen litterin situ. Thus, we do not know whether the drivers of its decomposition are similar to those for plant litter (e.g., importance of abiotic degradation through UV radiation), the magnitude of lichen decomposition rates and whether they will be affected by climate change. Here we report results from a litter decomposition experiment carried out with two biocrust-forming lichens (Diploschistes diacapsisandCladonia convoluta) in central Spain. We evaluated how lichen decomposition was affected by warming, rainfall exclusion and the combination of both. We also manipulated the incidence of UV radiation using mesh material that blocked 10% or 90% of incoming UV radiation. Our results indicate that lichens decompose as fast as some plants typical of the region (k~0.3) and that the chemical composition of their thallus drives litter decomposition rates. Warming increased decomposition rates of both lichen species, and mediated the effects of photodegradation. While UV exposure accelerated the decomposition ofD. diacapsis, it slowed down that ofC. convoluta. Our results indicate that biocrust-forming lichens can decompose in the field at a rate similar to that of vascular plants, and that this process will be affected by warming. Our findings further highlight the need of incorporating biocrusts into carbon cycling models to better understand and forecast climate change impacts on terrestrial biogeochemistry.
ConvDip: A convolutional neural network for better EEG Source Imaging
Authors: Hecker Lukas , Rupprecht Rebekka , van Elst Ludger Tebartz , Kornmeier Jürgen 
Published: April 2020

1AbstractThe EEG is a well-established non-invasive method in neuroscientific research and clinical diagnostics. It provides a high temporal but low spatial resolution of brain activity. In order to gain insight about the spatial dynamics of the EEG one has to solve the inverse problem, i.e. finding the neural sources that give rise to the recorded EEG activity. The inverse problem is ill-posed, which means that more than one configuration of neural sources can evoke one and the same distribution of EEG activity on the scalp. Artificial neural networks have been previously used successfully to find either one or two dipoles sources. These approaches, however, have never solved the inverse problem in a distributed dipole model with more than two dipole sources. We present ConvDip, a novel convolutional neural network (CNN) architecture that solves the EEG inverse problem in a distributed dipole model based on simulated EEG data. We show that (1) ConvDip learned to produce inverse solutions from a single time point of EEG data and (2) outperforms state-of-the-art methods on all focused performance measures. It is more flexible when dealing with varying number of sources, produces less ghost sources and misses less real sources than the comparison methods. It produces plausible inverse solutions for real EEG recordings from human participants. (4) The trained network needs less than 40 ms for a single prediction. Our results qualify ConvDip as an efficient and easy-to-apply novel method for source localization in EEG data, with high relevance for clinical applications, e.g. in epileptology and real time applications.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein harbors a conserved BH3-like sequence
Authors: Navratil Vincent , Lionnard Loïc , Longhi Sonia , Hardwick J. Marie , Combet Christophe , Aouacheria Abdel 
Published: April 2020

Disclaimer textThe authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Ciprofloxacin Resistance in Hospital and Community-acquired Urinary Tract Infections by Escherichia coli: A Systematic Review and Meta-analysis
Authors: Zhou Guanyu , Lv Xiaoju 
Published: April 2020

AbstractIn recent years, antimicrobial resistance has been increasingly reported. One main concern is the resistance of gram-negative bacteria like E. coli to ciprofloxacin (fluoroquinolones). Gram-negative bacteria are the main cause of community and hospital-acquired urinary tract infections (UTI). We aimed to review and analyze the data on ciprofloxacin resistance in hospital and community-acquired UTI. A literature search of three electronic databases (PubMed, Medline, and Cochrane) was performed. We considered the papers that were published from January 2004 to May 2019. The search yielded a total of 16097 studies besides 31 studies from a manual search. Filtering yielded 1297 relevant full-text papers. Eighty-three papers, equivalent of 99 cohorts, were finally included in this systematic review and in the analysis. The analysis results suggest that pooled ciprofloxacin resistance for community and hospital-acquired E. coli UTI is 0.27 (95% CI 0.246–0.303) and 0.30 (95% CI 0.22–0.38), respectively. Pooled resistance rates according to regions are 0.43 (95% CI 0.31–0.54) for Asia ensued by Africa 0.31 (95% CI 0.22–0.35), the Middle East 0.21(95% CI 0.13-0.30), Europe 0.18 (95% CI 0.13-0.22), and Australia 0.06 (95% CI 0.04-0.08). The pooled estimates revealed that ciprofloxacin resistance was higher in developing countries compared to that in developed countries, 0.35 (95% CI 0.30-0.40) and 0.13 (95% CI 0.10-0.16), respectively. Finally, plotting resistance over time deemed statistically significant (n= 79, r= 0.29,p= 0.038). Our findings suggest that ciprofloxacin resistance among UTI patients is a highly prevalent and serious issue. The suggested risks are low-income, acquiring hospital infection, and falling in highly-vulnerable regions like Asia and Africa. We also shed light on some approaches to correct the perception of patients and general practitioners (GPs) for antibiotic usage. We also suggest ideas to impede the progress of the post-antibiotic era in countries known for high antibiotic resistance.
A novel luminescence-based β-arrestin membrane recruitment assay for unmodified GPCRs
Authors: Pedersen Maria Hauge , Pham Jennifer , Mancebo Helena , Inoue Asuka , Javitch Jonathan A. 
Published: April 2020

AbstractG protein-coupled receptors (GPCRs) signal through activation of G proteins and subsequent modulation of downstream effectors. More recently, G protein-independent signaling via the arrestin pathway has also been implicated in important physiological functions. This has led to great interest in the identification of biased ligands that favor either the G protein or arrestin-signaling pathways. Currently available screening techniques that measure arrestin recruitment have required C-terminal receptor modifications that can in principle alter protein interactions and thus signaling. Here, we have developed a novel luminescence-based assay to measure arrestin recruitment to any unmodified receptor.NanoLuc, an engineered luciferase fromophlorus gracilirostris(deep sea shrimp), is smaller and brighter than other well-established luciferases. Recently, several publications have explored functional NanoLuc split sites for use in complementation assays. Here, we have identified a novel split site and have fused the N-terminal fragment to a membrane tether and the C-terminal fragment to the N-terminus of either β-arrestin 1 or 2. Upon receptor activation, arrestin is recruited to the plasma membrane in an agonist concentration-dependent manner and the two NanoLuc fragments complement to reconstitute functional luciferase, which allows quantification of recruitment with a single luminescence signal. Our assay avoids potential artifacts related to C-terminal receptor modification. The split NanoLuc arrestin recruitment assay has promise as a new generic assay for measuring arrestin recruitment to diverse GPCR types in heterologous or native cells.
bHLH11 inhibits bHLH IVc proteins by recruiting the TOPLESS/TOPLESS-RELATED corepressors in Arabidopsis
Authors: Li Yang , Lei Rihua , Pu Mengna , Cai Yuerong , Lu Chengkai , Li Zhifang , Liang Gang 
Published: April 2020

ABSTRACTIron (Fe) homeostasis is essential for plant growth and development. Many transcription factors play pivotal roles in the maintenance of Fe homeostasis. bHLH11 was identified as a negative transcription factor regulating Fe homeostasis, however, the underlying molecular mechanism remains elusive. We generated two loss-of-functionbhlh11mutants which display the enhanced sensitivity to Fe excess, the increased Fe accumulation and the elevated expression of Fe deficiency responsive genes. bHLH11 protein, localized in both the cytoplasm and nucleus, decreases in response to Fe deficiency. Coexpression assays indicate that bHLH IVc transcription factors (TFs) (bHLH34, bHLH104, bHLH105, and bHLH115) facilitate the nuclear accumulation of bHLH11 protein. Further analysis indicates that bHLH11 represses the transactivity of bHLH IVc TFs towards bHLH Ib genes (bHLH38, bHLH39, bHLH100, andbHLH101). bHLH11 contains two EAR motifs which are responsible for the repression function by recruiting the TOPLESS/TOPLESS-RELATED (TPL/TPRs) corepressors. Correspondingly, the expression of Fe uptake genes increases in thetpr1 tpr4 tplmutant. Moreover, genetic analysis reveals that bHLH11 has functions independent of FIT. This study provides insights into the complicate Fe homeostasis signaling network.One-sentence summarybHLH IVc proteins promote the bHLH11 protein accumulation in the nucleus where bHLH11 inhibits the transcriptional activation ability of bHLH IVc via its EAR motifs recruiting the TOPLESS/TOPLESS-RELATED corepressors.
The 3.2Å resolution structure of human mTORC2
Authors: Scaiola Alain , Mangia Francesca , Imseng Stefan , Boehringer Daniel , Berneiser Karolin , Shimobayashi Mitsugu , Stuttfeld Edward , Hall Michael N. , Ban Nenad , Maier Timm 
Published: April 2020

AbstractThe protein kinase mammalian target of rapamycin (mTOR) is the central regulator of cell growth. Aberrant mTOR signaling is linked to cancer, diabetes and neurological disorders. mTOR exerts its functions in two distinct multiprotein complexes, mTORC1 and mTORC2. Here we report a 3.2 Å resolution cryo-EM reconstruction of mTORC2. It reveals entangled folds of the defining Rictor and the substrate-binding SIN1 subunits, identifies the C-terminal domain of Rictor as the source of the rapamycin insensitivity of mTORC2, and resolves mechanisms for mTORC2 regulation by complex destabilization. Two novel small molecule binding sites are visualized, an inositol hexakisphosphate (InsP6) pocket in mTOR and an mTORC2-specific nucleotide binding site in Rictor which also forms a zinc finger. Structural and biochemical analyses suggest that InsP6 and nucleotide binding do not control mTORC2 activity directly but rather have roles in folding or ternary interactions. These insights provide a firm basis for studying mTORC2 signaling and for developing mTORC2-specific inhibitors.
DEBay: a computational tool for deconvolution of quantitative PCR data for estimation of cell type-specifc gene expression in a mixed population
Authors: Devaraj Vimalathithan , Bose Biplab 
Published: April 2020

AbstractThe expression of a gene is commonly estimated by quantitative PCR (qPCR) using RNA isolated from a large number of pooled cells. Such pooled samples often have subpopulations of cells with different levels of expression of the target gene. Estimation of gene expression from an ensemble of cells obscures the pattern of expression in different subpopulations. Physical separation of various subpopulations is a demanding task. We have developed a computational tool, Deconvolution of Ensemble through Bayes-approach (DEBay), to estimate cell type-specific gene expression from qPCR data of a mixed population. DEBay estimates Normalized Gene Expression Coefficient (NGEC), which is a relative measure of the expression of the target gene in each cell type in a population. NGEC has a direct algebraic correspondence with the normalized fold change in gene expression measured by qPCR. DEBay can deconvolute both time-dependent and -independent gene expression profiles. It uses the Bayesian method of model selection and parameter estimation. We have evaluated DEBay using synthetic and real experimental data. DEBay is implemented in Python. A GUI of DEBay and its source code are available for download at SourceForge (https://sourceforge.net/projects/debay).