bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pitfalls and solutions in case fatality risk estimation – A multi-country analysis on the role of demographics, surveillance, time lags between reporting and death and healthcare system capacity on COVID-19
Authors: Vanella Patrizio , Wiessner Christian , Holz Anja , Krause Gérard , Möhl Annika , Wiegel Sarah , Lange Berit , Becher Heiko 
Published: May 2020

AbstractEuropean countries report large differences in COVID-19 case fatality risk (CFR) and high variation over the year. CFR estimates may both depend on the method used for estimation and of country-specific characteristics. While crude methods simply use cumulative total numbers of cases and deaths, the CFR can be influenced by the demographic characteristics of the cases, case detection rates, time lags between reporting of infections and deaths and infrastructural characteristics, such as healthcare capacities.We used publicly available weekly data from the national health authorities of Germany, Italy, France and Spain on case and death numbers by age group connected to COVID-19 for the year 2020. We propose to use smoothed data of national weekly test rates for case adjustment and investigated the impact of different time lags from case reporting to death on the estimation of the CFR. Finally, we described the association between case fatality and the demand for hospital beds for COVID-19, taking into account national hospital bed capacities.Crude CFR estimates differ considerably between the four study countries with end-of-year values of approximately 1.9%, 3.5%, 2.5% and 2.7% for Germany, Italy, France and Spain, respectively. Age-adjustment reduces the differences considerably, resulting in values of 1.61%, 2.4% and 2% for Germany, Italy and Spain, respectively. France’s age-specific data was restricted to hospitalised cases only and is therefore not comparable in that regard. International crude International CFR time series show smaller differences when adjusting for demographics of the cases or the test rates. Curves adjusted for age structure, testing or time lags show smaller variance over the year and a smaller degree of non-stationarity. The data does not suggest any connection of CFRs to hospital capacities for the four countries under study.
Local propagation dynamics of MEG interictal spikes: source reconstruction with traveling wave priors
Authors: Kuznetsova Aleksandra , Lebedev Mikhail , Ossadtchi Alexei 
Published: May 2020

AbstractEpilepsy is one of the most common neurological disorders, with about 30% of cases being drug-resistant and requiring surgical intervention. To localize the epileptogenic zone (EZ), the pathological area that has to be surgically removed, brain regions are inspected for the presence of spikes during the interictal periods. This procedure maps irritative zones where spikes are present, but it is still challenging to determine which of the irritative zones generate seizures. To localize the source of seizures more precisely, a large-scale approach could be applied where the causal relationship is assessed between the signals recorded in a finite number of irritative zones [27]. This method however, does not reveal the fine-grained spatiotemporal patterns of spikes, which could provide valuable information regarding EZ location and increase the likelihood of surgery success [33].Here we present a framework to noninvasively investigate the fine patterns of interictal spikes present in magnetoencephalographic (MEG) data. We use a traveling wave model, previously employed in the analysis of cortical alpha oscillations [16], to regularize the MEG inverse problem and to determine the cortical paths of spike traveling waves. Our algorithm represents spike propagation patterns as a superposition of local waves traveling along radial paths stemming from a single origin. With the help of the positively constrained LASSO technique we scan over wave onset moment and propagation velocity parameters to determine their combination that yields the best fit to the MEG sensor data of each spike.We first used realistically simulated MEG data to validate the algorithm ability to successfully track interictal activity on a millimeter-millisecond scale. Next, we examined MEG data from three patients with drug-resistant epilepsy. Wave-like spike patterns with clear propagation dynamics were found in a fraction of spikes, whereas the other fraction could not be explained by the wave propagation model with a small number of propagation directions. Moreover, in agreement with the previous work [33], the spike waves with clear propagation dynamics exhibited spatial segregation and matched the clinical records on seizure onset zones (SOZs) available for two patients out of three.
Dynamic meta-analysis: a method of using global evidence for local decision making
Authors: Shackelford Gorm E. , Martin Philip A. , Hood Amelia S. C. , Christie Alec P. , Kulinskaya Elena , Sutherland William J. 
Published: May 2020

AbstractMeta-analysis is often used to make generalizations across all available evidence at the global scale. But how can these global generalizations be used for evidence-based decision making at the local scale, if only the local evidence is perceived to be relevant to a local decision? We show how an interactive method of meta-analysis — dynamic meta-analysis — can be used to assess the local relevance of global evidence. We developed Metadataset (www.metadataset.com) as an example of dynamic meta-analysis. Using Metadataset, we show how evidence can be filtered and weighted, and results can be recalculated, using dynamic methods of subgroup analysis, meta-regression, and recalibration. With an example from agroecology, we show how dynamic meta-analysis could lead to different conclusions for different subsets of the global evidence. Dynamic meta-analysis could also lead to a rebalancing of power and responsibility in evidence synthesis, since evidence users would be able to make decisions that are typically made by systematic reviewers — decisions about which studies to include (e.g., critical appraisal) and how to handle missing or poorly reported data (e.g., sensitivity analysis). We suggest that dynamic meta-analysis could be scaled up and used for subject-wide evidence synthesis in several scientific disciplines (e.g., agroecology and conservation biology). However, the metadata that are used to filter and weight the evidence would need to be standardized within disciplines.
Investigation of biological activities ofColocasia giganteaHook.f. leaves and PASS prediction, in silico molecular docking with ADME/T analysis of its isolated bioactive compounds
Authors: Alam Safaet , Emon Nazim Uddin , Rashid Mohammad A. , Arman Mohammad , Haque Mohammad Rashedul 
Published: May 2020

AbstractBackgroundColocasia giganteais locally named as kochu and also better known due to its various healing power. This research is to investigate the antidiarrheal, antimicrobial, and antioxidant possibilities of the methanol soluble extract ofColocasia gigantea.MethodsAntidiarrheal investigation was performed by usingin vivocastor oil induced diarrheal method where asin vitroantimicrobial and antioxidant investigation have been implemented by disc diffusion and DPPH scavenging method respectively. Moreover,in silicostudies were followed by molecular docking analysis of several secondary metabolites were appraised with Schrödinger-Maestro v 11.1.ResultsThe induction of plant extract (200 and 400 mg/kg, b.w, p.o), the castor oil mediated diarrhea has been minimized 19.05 % (p < 0.05) and 42.86 % (p < 0.001) respectively. The methanolic extract ofC. giganteashowed mild sensitivity against almost all the tested strains but it shows high consistency of phenolic content and furthermore yielded 67.68 μg/mL of IC50value in the DPPH test. The higher and lower binding affinity was shown in beta-amyrin and monoglyceryl stearic acid against the kappa-opioid receptor (PDB ID: 4DJH) with a docking score of -3.28 kcal/mol and -6.64 kcal/mol respectively. In the antimicrobial investigation, Penduletin and Beta-Amyrin showed the highest and lowest binding affinity against the selected receptors with the docking score of -8.27 kcal/mol and -1.66 kcal/mol respectively.ConclusionThe results of our scientific research reflect that the methanol soluble extract ofC. giganteais safe which may provide possibilities of alleviation of diarrhea and as a potential wellspring of antioxidants which can be considered as an alternate source for exploration of new medicinal products.
Kinship, acquired and inherited status, and population structure at the Early Bronze Age Mokrin necropolis in northern Serbia
Authors: Žegarac Aleksandra , Winkelbach Laura , Blöcher Jens , Diekmann Yoan , Gavrilović Marija Krečković , Porčić Marko , Stojković Biljana , Milašinović Lidija , Schreiber Mona , Wegmann Daniel , Veeramah Krishna R. , Stefanović Sofija , Burger Joachim 
Published: May 2020

AbstractTwenty-four ancient genomes with an average sequencing coverage of 0.85±0.25 X were produced from the Mokrin necropolis, an Early Bronze Age (2,100-1,800 BC) Maros culture site in Serbia, to provide unambiguous identification of biological sex, population structure, and genetic kinship between individuals. Of the 24 investigated individuals, 15 were involved in kinship relationships of varying degrees, including 3 parent-offspring relationships. All observed parent-offspring pairs were mother and son. In addition to the absence of biological daughters, we observed a number of young women and girls with no biological relatives in our sample. These observations, together with the high mitochondrial diversity in our sample, are consistent with the practice of female exogamy in the population served by Mokrin. However, moderate-to-high Y-chromosomal diversity suggests a degree of male mobility greater than that expected under strict patrilocality. Individual status differences at Mokrin, as indicated by grave goods, support the inference that females could inherit status, but could not transmit status to all their sons. The case of a son whose grave good richness outstrips that of his biological mother suggests that sons had the possibility to acquire status during their lifetimes. The Mokrin sample resembles a genetically unstructured population, suggesting that the community’s social hierarchies were not accompanied by strict marriage barriers.
An ex vivo model ofToxoplasmarecrudescence
Authors: Goerner Amber L. , Vizcarra Edward A. , Hong David D. , Bergersen Kristina V. , Alvarez Carmelo A. , Talavera Michael A. , Wilson Emma H. , White Michael W. 
Published: May 2020

ABSTRACTToxoplasmahas been a useful parasite model for decades because it is relatively easy to genetically modify and culture, however, attempts to generate and study the recrudescence of tissue cysts have come up short with lab-adapted strains generating low numbers of tissue cysts in vivo. Here we have established a new model ofToxoplasmarecrudescence using bradyzoites from an unadapted Type II ME49 strain (ME49EW) isolated from murine brain tissue. Ex vivo bradyzoite infection of fibroblasts and astrocytes produced sequential tachyzoite growth stages; a fast-growing stage was followed by formation of a slower-growing stage. In astrocytes, but not in fibroblasts, bradyzoites also initiated a second recrudescent pathway involving bradyzoite to bradyzoite replication. Intraperitoneal infections of mice with either bradyzoites or the fast-growing tachyzoite stage efficiently disseminated to brain tissue leading to high numbers of tissue cysts, while infections with the slow-growing tachyzoite stage were largely retained in the peritoneum. Poor infection and cyst formation of slow-growing tachyzoites was reversible by serial tissue cyst passage, while the poor tissue cyst formation of lab-adapted tachyzoites was not reversible by these approaches. To distinguish strain developmental competency, we identifiedToxoplasmagenes highly expressed in ME49EW in vivo tissue cysts and developed a qPCR approach that differentiates immature from mature bradyzoites. In summary, the results presented describe a new ex vivo bradyzoite recrudescence model that fully captures the growth and developmental processes during toxoplasmosis reactivation in vivo opening the door to the further study of these important features of theToxoplasmaintermediate life cycle.
Dissemination of Carbapenem-resistance and Plasmids-encoding Carbapenemases in Gram-negative Bacteria Isolated from India
Authors: Manohar Prasanth , Leptihn Sebastian , Lopes Bruno S. , Ramesh Nachimuthu 
Published: May 2020

AbstractCarbapenem resistance in Gram-negative bacteria is an ongoing public-health problem of global dimensions leaving very few treatment options for severely infected patients. This study focuses on the dissemination of plasmid-borne carbapenemase genes in Gram-negative bacteria in Tamil Nadu, India. A total of 151 non-repetitive isolates belonging to 11 genera were collected from a diagnostic center in Tamil Nadu.E. coli(n=57) isolates were classified as, Enteropathogenic (n=12), Enteroaggregative (n=9), Enterohemorrhagic (n=8), Enterotoxigenic (n=3), Enteroinvasive (n=1) and unclassifiedE. coli(n=24). Of the 45Klebsiellaspecies, 14 were K1 whereas 11 were K2 serotype and in 20Klebsiellaserotype could not be determined. Other isolates (n=49) consisted ofP. aeruginosa,S. typhi,E. cloacae,A. baumannii,S. marcescens,A. xylosoxidans,P. mirabilisandE. meningoseptica. Of the 151 isolates, 71% (n=107) and 68% (n=103) were found to be resistant to meropenem and imipenem respectively. The most prevalent beta-lactamase gene wasblaNDM-1(21%, 12/57) followed byblaOXA-181(16%, 9/57),blaGES-9(n=8),blaOXA-23(n=7),blaIMP-1(n=3),blaGES-1(n=11) andblaOXA-51(n=9). The unusual presence ofblaOXA-23was seen inE. coli(n=4), andblaOXA-23andblaOXA-51(IncA/C) inK. pneumoniae(n=3). Plasmid incompatibility (inc/rep) typing results showed that the plasmids carrying resistance genes (n=11) belonged to IncX, IncA/C, IncFIA-FIB and IncFIIA groups.E. coliandK. pneumoniaewere able to transfer plasmid-borne carbapenemase via conjugation. This study highlights the prevalence of carbapenem resistance and the acquisition of plasmid-borne carbapenemase genes in Gram-negative bacteria highlighting the role of plasmid transfer in disseminating resistance.
Phytoplankton trigger the production of cryptic metabolites in the marine actinobacteriaSalinispora tropica
Authors: Chhun Audam , Sousoni Despoina , del Mar Aguiló-Ferretjans Maria , Song Lijiang , Corre Christophe , Christie-Oleza Joseph A. 
Published: May 2020

AbstractBacteria from the Actinomycete family are a remarkable source of natural products with pharmaceutical potential. The discovery of novel molecules from these organisms is, however, hindered because most of the biosynthetic gene clusters (BGCs) encoding these secondary metabolites are cryptic or silent and are referred to as orphan BGCs. While co-culture has proven to be a promising approach to unlock the biosynthetic potential of many microorganisms by activating the expression of these orphan BGCs, it still remains an underexplored technique. The marine actinobacteriaSalinispora tropica, for instance, produces valuable compounds such as the anti-cancer molecule salinosporamide A but half of its putative BGCs are still orphan. Although previous studies have looked into using marine heterotrophs to induce orphan BGCs inSalinispora, the potential impact of co-culturing marine phototrophs withSalinisporahas yet to be investigated. Following the observation of clear antimicrobial phenotype of the actinobacterium on a range of phytoplanktonic organisms, we here report the discovery of novel cryptic secondary metabolites produced byS. tropicain response to its co-culture with photosynthetic primary producers. An approach combining metabolomics and proteomics revealed that the photosynthate released by phytoplankton influences the biosynthetic capacities ofS. tropicawith both production of new molecules and the activation of orphan BGCs. Our work pioneers the use of phototrophs as a promising strategy to accelerate the discovery of novel natural products from actinobacteria.ImportanceThe alarming increase of antimicrobial resistance has generated an enormous interest in the discovery of novel active compounds. The isolation of new microbes to untap novel natural products is currently hampered because most biosynthetic gene clusters (BGC) encoded by these microorganisms are not expressed under standard laboratory conditions,i.e.mono-cultures. Here we show that co-culturing can be an easy way for triggering silent BGC. By combining state-of-the-art metabolomics and high-throughput proteomics, we characterized the activation of cryptic metabolites and silent biosynthetic gene clusters in the marine actinobacteriaSalinispora tropicaby the presence of phytoplankton photosynthate. We further suggest a mechanistic understanding of the antimicrobial effect this actinobacterium has on a broad range of prokaryotic and eukaryotic phytoplankton species and reveal a promising candidate for antibiotic production.
Normalization of single-cell RNA-seq counts by log(x+1)* or log(1+x)*
Authors: Booeshaghi A. Sina , Pachter Lior 
Published: May 2020

AbstractSingle-cell RNA-seq technologies have been successfully employed over the past decade to generate many high resolution cell atlases. These have proved invaluable in recent efforts aimed at understanding the cell type specificity of host genes involved in SARS-CoV-2 infections. While single-cell atlases are based on well-sampled highly-expressed genes, many of the genes of interest for understanding SARS-CoV-2 can be expressed at very low levels. Common assumptions underlying standard single-cell analyses don’t hold when examining low-expressed genes, with the result that standard workflows can produce misleading results.Key PointsLowly expressed genes in single-cell RNA-seq can be easliy misanalyzed.log(1+x) count normalization introduces errors for lowly expressed genesThe average log(1+x) expression differs considerably from log(x) when x is smallAn alternative approach is to use the fraction of cells with non-zero expression
Ribo-Pop: Simple, cost-effective, and widely applicable ribosomal RNA depletion
Authors: Thompson Mary Kay , Kiourlappou Maria , Davis Ilan 
Published: May 2020

ABSTRACTThe measurement of RNA abundance derived from massively parallel sequencing experiments is an essential technique. Methods that reduce ribosomal RNA levels are usually required prior to sequencing library construction because ribosomal RNA typically comprises the vast majority of a total RNA sample. For some experiments, ribosomal RNA depletion is favored over poly(A) selection because it offers a more inclusive representation of the transcriptome. However, methods to deplete ribosomal RNA are generally proprietary, complex, inefficient, applicable to only specific species, or compatible with only a narrow range of RNA input levels. Here, we describe Ribo-Pop (ribosomal RNA depletion for popular use), a simple workflow and antisense oligo design strategy that we demonstrate works over a wide input range and can be easily adapted to any organism with a sequenced genome. We provide a computational pipeline for probe selection, a streamlined 20-minute protocol, and ready-to-use oligo sequences for several organisms. We anticipate that our simple and generalizable “open source” design strategy would enable virtually any lab to pursue full transcriptome sequencing in their organism of interest with minimal time and resource investment.
Using targeted genome integration for virus-free genome-wide mammalian CRISPR screen
Authors: Xiong Kai , Karottki Karen Julie la Cour , Hefzi Hooman , Li Songyuan , Grav Lise Marie , Li Shangzhong , Spahn Philipp , Lee Jae Seong , Lee Gyun Min , Kildegaard Helene Faustrup , Lewis Nathan E. , Pedersen Lasse Ebdrup 
Published: May 2020

ABSTRACTPooled CRISPR screens have been widely applied in mammalian cells to discover genes regulating various phenotypes of interest. In such screens, CRISPR components are generally delivered with a lentivirus. However, lentiviral CRISPR screens are limited by unpredictable genome insertion, the requirement of biosafety level II lab facilities and personnel trained to work with viruses. Here we established a virus-free (VF) genome-wide CRISPR screening platform for Chinese hamster ovary (CHO) cells with 74,617 gRNAs targeting 18,353 genes. Each gRNA expression cassette in the library is precisely integrated into a genomic landing pad thus reducing the clonal variation. Using this VF CRISPR screening platform, 338 genes are identified as essential for CHO cell growth and 76 genes were found to be involved in the unfolded protein response (UPR) induced endoplasmic reticulum (ER) stress. Extensive validation of the candidate genes further demonstrated the robustness of this novel non-viral CRISPR screen method.
Cryptic prophages within aStreptococcus pyogenesgenotypeemm4 lineage
Authors: Remmington Alex , Haywood Samuel , Edgar Julia , Turner Claire E. 
Published: May 2020

AbstractThe major human pathogenStreptococcus pyogenesshares an intimate evolutionary history with mobile genetic elements, which in many cases, carry genes encoding bacterial virulence factors. During recent whole genome sequencing of a longitudinal sample ofS. pyogenesisolates in the United Kingdom, we identified a lineage withinemm4 that clustered with the reference genome MEW427. Like MEW427, this lineage was characterised by substantial gene loss within all three prophage regions, compared to MGAS10750 and isolates outside of the MEW427-like lineage. Gene loss primarily affected lysogeny, replicatory and regulatory modules, and to a lesser and more variable extent, structural genes. Importantly, prophage-encoded superantigen and DNase genes were retained in all isolates. In isolates where the prophage elements were complete, like MGAS10750, they could be induced experimentally, but not in MEW427-like isolates with degraded prophages. We also found gene loss within the chromosomal island SpyCIM4 of MEW427-like isolates, although surprisingly, the SpyCIM4 element could not be experimentally induced in either MGAS10750-like or MEW427-like isolates. This did not, however, appear to abolish expression of the mismatch repair operon, within which this element resides. The inclusion of furtheremm4 genomes in our analyses ratified our observations and revealed an internationalemm4 lineage characterised by prophage degradation. Intriguingly, the USA population ofemm4S. pyogenesappeared to constitute predominantly MEW427-like isolates, whereas the UK comprised both MEW427-like and MGAS10750-like strains. The degradation and cryptic nature of these elements may have important phenotypic ramifications foremm4S. pyogenesand the geographical distribution of this lineage raises interesting questions on the population dynamics of the genotype.Data summaryAll raw sequence data used in this study has been previously published and was obtained from NCBI short read archive. Accession numbers and citations for the genome data for each individual isolate is provided in Supplementary Table 1.