bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new ischemic grading system to aid combat extremity vascular injury decision making
Authors: Ratnayake Amila , Reva Viktor A. , Bala Miklosh , Jayatilleke Achala U. , Thalgaspitiya Sujeewa P.B. , Kauvar David S. , Worlton Tamara J. 
Published: August 2020

AbstractIntroductionIn resource limited combat settings with frequent encounters of mass casualty incidents, the decision to attempt limb salvage versus primary amputation is refined over time based on experience. This experience can be augmented by grading systems and algorithms to assist in clinical decisions. Few investigators have attempted to explicitly grade limb ischemia according to clinical criteria and study the impact of limb ischemia on clinical outcome. We suggest a new ischemia grading system based on the Rutherford ischemic classification and the V. A. Kornilov classification which we adapted to apply to the combat setting. This new tool was then retrospectively applied to combat trauma patients from the Sri Lankan Civil War.MethodWe retrospectively queried a prospectively maintained, single surgeon registry containing 129 extremity vascular injuries managed at a Role 3 military base hospital (MBH) from 2008 December to June 2009 during the last phase of Sri Lankan Civil war. 89 patients were analyzed for early limb salvage according to the modified Kornilov extremity ischemia index (MKEII).ResultAccording to the MKEII, subcohort analysis of C1 (viable), C2 (threatened), and C3 (irreversible) classified injuries demonstrated a statistically significant (P < 0.001) difference in limb salvage. Further statistical evaluation demonstrated injury to popliteal region (P=0.006), severe arterial injury (P=0.018) and venous injuries (P< 0.001) had statistically significant differences in distribution between C1, C2 and C3.ConclusionBy application of the MKEII, combat surgeons can rapidly and correctly select and prioritize vascular injured extremities to optimally use limited resources to achieve realistic limb salvage goals. A rigid ankle was correlated with the worst index of extremity ischemia. Further investigation into this sign as an indication for primary amputation is warranted.
HOW, WHY AND UNDER WHAT CIRCUMSTANCES DOES A QUALITY IMPROVEMENT COLLABORATIVE BUILD KNOWLEDGE AND SKILLS IN CLINICIANS WORKING WITH PEOPLE WITH DEMENTIA? A REALIST INFORMED PROCESS EVALUATION
Authors: de la Perrelle Lenore , Cations Monica , Barbery Gaery , Radisic Gorjana , Kaambwa Billingsley , Crotty Maria , Fitzgerald Janna Anneke , Kurrle Susan , Cameron Ian D , Whitehead Craig , Thompson Jane , Laver Kate 
Published: August 2020

AbstractIn increasingly constrained health and aged care services, strategies are needed to improve quality and translate evidence into practice. In dementia care, recent failures in quality and safety have led the World Health Organisation to prioritise the translation of known evidence into practice. While quality improvement collaboratives have been widely used in healthcare, there are few examples in dementia care.We describe a recent quality improvement collaborative to improve dementia care across Australia and assess the implementation outcomes of acceptability and feasibility of this strategy to translate known evidence into practice. A realist-informed process evaluation was used to analyse how, why and under what circumstances a quality improvement collaborative built knowledge and skills in clinicians working in dementia care.This realist-informed process evaluation developed, tested, and refined the program theory of a quality improvement collaborative. Data were collected pre-and post-intervention using surveys and interviews with participants (n=24). A combined inductive and deductive data analysis process integrated three frameworks to examine the context and mechanisms of knowledge and skill building in participant clinicians.A refined program theory showed how and why clinicians built knowledge and skills in quality improvement in dementia care. Seven mechanisms were identified: motivation, accountability, identity, collective learning, credibility, and reflective practice. Each of these mechanisms operated differently according to context.A quality improvement collaborative designed for clinicians in different contexts and roles was acceptable and feasible in building knowledge and skills of clinicians to improve dementia care. A supportive setting and a credible, flexible, and collaborative process optimises quality improvement knowledge and skills in clinicians working with people with dementia.Trial registrationAustralian and New Zealand Clinical Trials Registry 21 February 2018 (ACTRN 12618000268246)
Aggregation Tool for Genomic Concepts (ATGC): A deep learning framework for somatic mutations and other sparse genomic measures
Authors: Anaya Jordan , Sidhom John-William , Mahmood Faisal , Baras Alexander S. 
Published: August 2020

ABSTRACTDeep learning can extract meaningful features from data given enough training examples. Large-scale genomic data are well suited for this class of machine learning algorithms; however, for many of these data the labels are at the level of the sample instead of at the level of the individual genomic measures. Conventional approaches to this data statically featurise and aggregate the measures separately from prediction. We propose to featurise, aggregate, and predict with a single trainable end-to-end model by turning to attention-based multiple instance learning. This allows for direct modelling of instance importance to sample-level classification in addition to trainable encoding strategies of genomic descriptions, such as mutations. We first demonstrate this approach by successfully solving synthetic tasks conventional approaches fail. Subsequently we applied the approach to somatic variants and achieved best-in-class performance when classifying tumour type or microsatellite status, while simultaneously providing an improved level of model explainability. Our results suggest that this framework could lead to biological insights and improve performance on tasks that aggregate information from sets of genomic data.
New insights of zoogeographical distribution of Himalayan goral (Naemorhedus goral) from Indian Himalayan Region
Authors: Joshi Bheem Dutt , Singh Vinay Kumar , Singh Hemant , Singh Ashutosh , Singh Sujeet Kumar , Chandra Kailash , Sharma Lalit Kumar , Thakur Mukesh 
Published: August 2020

ABSTRACTIn the present study, we explored the intraspecific genetic variation and phylogeographic relationship among all the reported species in the genusNaemorhedusdistributed in a wide range of habitats. The Bayesian based phylogeny demonstrated that Himalayan goral, is a highly diverged species from the other reported species of gorals. We claim the presence of two valid sub-species of Himalayan goral, i.e.N. g. bedfordiandN. g. goral, distributed in the western and central Himalaya, respectively. The comparative analysis with the inclusion of data available from different ranges, suggests the presence of plausibly six species of gorals across the distribution with a few valid subspecies. Further, we report thatN. griseusis a valid species and not the synonyms ofN. goralconsidering the observed discrepancy in the available sequences. We recommend all the sub-species present at distant locations may be considered as Evolutionary Significant Units (ESUs) and, therefore, appeal to provide them special attention for long term conservation and management.
Genomic investigation of a suspected multi-drug resistantKlebsiella pneumoniaeoutbreak in a neonatal care unit in sub-Saharan Africa
Authors: Cornick Jennifer , Musicha Patrick , Peno Chikondi , Saeger Ezgi , Toh Pui-ying Iroh , Bennett Aisleen , Kennedy Neil , Feasey Nicholas , Heinz Eva , Cain Amy K. 
Published: August 2020

ABSTRACTA suspected outbreak of multi-drug resistant (MDR)Klebsiella pneumoniaein a Malawian neonatal unit was investigated using whole-genome sequencing. Strain-types, virulence and resistance genes ofK. pneumoniaeisolated from patients from the hospital over a four-year period were identified. A MDR ST340 clone was implicated as the likely outbreak cause.
Modelling the interaction between Infectious Bursal Disease Virus VP3 polypeptide and dsRNA: identification of key residues for ribonucleoprotein assembly and virus replication
Authors: Busnadiego Idoia , Martín Maria T , Ferrero Diego S , de la Blanca María G Millán , Broto Laura , Díaz-Beneitez Elisabeth , Fuentes Daniel , Rodríguez Dolores , Verdaguer Nuria , Kremer Leonor , Rodríguez José F. 
Published: August 2020

ABSTRACTThe interaction of the structural VP3 polypeptide of infectious bursal disease virus (IBDV) with virus-encoded dsRNA is essential both for the assembly of ribonucleoprotein complexes responsible for genome transcription and replication and for the evasion of host’s antiviral responses. Surface plasmon resonance analysis allowed us to determine the kinetic constants of the VP3-dsRNA interaction as well as to map the VP3 dsRNA bipartite dsRNA binding domain (dsRBD), uncovering the specific role of the previously described Patch1 and Patch2 dsRB subdomains. Here we show that the Patch1 domain plays a primary binding function while Patch2 exerts a subordinate role stabilizing VP3-dsRNA complexes. The use of a set of VP3 mutant versions facilitated the identification of K99 and K106 within Patch1 as the essential residues for the formation of VP3-dsRNA complexes. Furthermore, replacement of either one of these two residues by aspartic acid completely thwarts both evasion from host’s sensors and virus replication. Data presented here allow us to propose a VP3-dsRNA interaction model that should help to further elucidate the mechanics of IBDV morphogenesis and genome packaging as well as to better understand how VP3 counteracts recognition of virus-encoded dsRNA by specialized host’s sensors.
Characterization of a sex-determining region and its genomic context via statistical estimates of haplotype frequencies in daughters and sons sequenced in pools
Authors: Cordaux Richard , Chebbi Mohamed Amine , Giraud Isabelle , Pleydell David , Peccoud Jean 
Published: August 2020

AbstractSex chromosomes are generally derived from a pair of autosomes that have acquired a locus controlling sex. Sex chromosomes usually evolve reduced recombination around this locus and undergo a long process of molecular divergence. Although sex chromosomes have been intensively studied in several model taxa, the actual loci controlling sex are difficult to identify in highly diverged sex chromosomes, hence they are known in relatively few species. Taxa with evolutionarily young sex chromosomes can help fill this gap in knowledge. Here we aimed at pinpointing the sex-determining region (SDR) of Armadillidium vulgare, a terrestrial isopod with female heterogamety (ZW females and ZZ males) and which presumably presents evolutionarily young sex chromosomes. To locate the SDR, we assessed SNP allele frequencies in F1 daughters and sons sequenced in pools (pool-seq) in several families. We developed a Bayesian method that uses the SNP genotypes of individually sequenced parents and poolseq data from F1 siblings to estimate the genetic distance between a given genomic region (contig) and the SDR. This allowed us to assign more than 43 Megabases of contigs to sex chromosomes. By taking advantage of the several F1 families, we delineated a very short genomic region (~65 kilobases) that did not show evidence for recombination with the SDR. In this region, the comparison of sequencing depths between sexes outlined female-specific genes that may be involved in sex determination. Overall, our results provide strong evidence for an extremely low divergence of sex chromosomes in A. vulgare.
Genomic evolutionary analysis in R with geaR
Authors: Ward Christopher M. , Ludington Alastair J. , Breen James , Baxter Simon W. 
Published: August 2020

AbstractThe analysis and interpretation of datasets generated through sequencing large numbers of individual genomes is becoming commonplace in population and evolutionary genetic studies. Here we introduce geaR, a modular R package for evolutionary analysis of genome-wide genotype data. The package leverages the Genomic Data Structure (GDS) format, which enables memory and time efficient querying of genotype datasets compared to standard VCF genotype files. geaR utilizes GRange object classes to partition an analysis based on features from GFF annotation files, select codons based on position or degeneracy, and construct both positional and coordinate genomic windows. Tests of genetic diversity (eg.dXY,π, FST) and admixturealong with tree building and sequence output, can be carried out on partitions using a single function regardless of sample ploidy or number of observed alleles. The package and associated documentation are available on GitHub athttps://github.com/CMWbio/geaR.
Successful reproduction ofTrachemys scriptain the Altrhein of Kehl (Germany) and simultaneous increase of estimated population size
Authors: Schradin Carsten 
Published: August 2020

ABSTRACTThe European Union categorised pond sliders (Trachemys scripta) as an invasive species for which all member countries have to develop an action plan. WhileT. scriptahas been released illegally in thousands of freshwaters in Europe, monitoring programs in Germany are missing. Based on short term surveys, anecdotal data, and assumptions, the action plan in Germany proposes thatT. scriptadoes not represent a problem as the cold weather causes high mortality and does not allow for successful reproduction. Here I present data of five years of monitoring at the Altrhein of Kehl, at the border between Germany and France showing: 1. Apart fromT. scripta, five additional species have been released (Pseudemys nelson, Pseudemys concinna, Graptemys pseudogeographica, Mauremys spec.,Chrysemys picta.). 2. Population size seemed to increase over the years, with 116 individuals being counted in 2020 compared to 33 individuals in 2016. 3. Successful reproduction of.T. scriptawas indicated by the observation of very small individuals and proved by the collection of hatchlings in two years. While the data presented here would benefit from more years of more intensive monitoring, they are sufficient to draw the conclusion that the German action plan is insufficient because individuals survive for long periods and do reproduce successfully. Similar results have been reported from other central European countries. Thus,T. scriptamight become invasive not only in south but also in central Europe. In sum, national action plans of how to deal with the invasiveT. scriptashould to be revised in Germany and many other European countries.
Diploid hepatocytes drive physiological liver renewal in adult humans
Authors: Heinke Paula , Rost Fabian , Rode Julian , Welsch Thilo , Alkass Kanar , Feddema Joshua , Salehpour Mehran , Possnert Göran , Druid Henrik , Brusch Lutz , Bergmann Olaf 
Published: August 2020

SummaryPhysiological liver cell replacement is central to maintaining the organ’s high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective14C birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, maintaining the liver a young organ (average age < 3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show an seven-fold higher annual exchange rate than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between these two subpopulations are limited, with minimal contribution to the respective other ploidy class under homeostatic conditions. With these findings, we present a new integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics.
Multivalent interactions between eIF4G1, Pub1 and Pab1 drive the formation of protein condensates
Authors: Chaves-Arquero Belén , Martínez-Lumbreras Santiago , Sibille Nathalie , Camero Sergio , Bernadó Pau , Jiménez Ma Ángeles , Zorrilla Silvia , Pérez-Cañadillas José Manuel 
Published: August 2020

SummaryYeast eIF4G1 interacts with RNA binding proteins (RBPs) like Pab1 and Pub1 affecting its function in translation initiation and stress granules formation. We present an NMR and SAXS study of the intrinsically disordered region of eIF4G1, eIF4G11-249, and its interactions with Pub1 and Pab1. The conformational ensemble of eIF4G11-249shows an α-helix within the BOX3 conserved element and a dynamic network of fuzzy π-π and π-cation interactions involving arginine and aromatic residues. The Pab1 RRM2 domain interacts with eIF4G1 BOX3, the canonical interaction site, but also with BOX2, a conserved element of unknown function to date. In contrast, the Pub1 RRM3 domain interacts with the RNA1-1 and BOX1 regions of eIF4G1. Mixtures of Pub1, Pab1 and eIF4G1 form micrometer-size protein condensates that require the presence of the eIF4G1 BOX1 element. These homotypic interactions suggest a double key mechanism of eIF4G1 regulation, important for understanding the architecture of stress granule cores.
Ribosome fingerprinting with a solid-state nanopore
Authors: Raveendran Mukhil , Leach Anna Rose , Hopes Tayah , Aspden Julie L. , Actis Paolo 
Published: August 2020

AbstractNanopores hold great potential for the analysis of complex biological molecules at the single entity level. One particularly interesting macromolecular machine is the ribosome, responsible for translating mRNA into proteins. In this study, we use a solid-state nanopore to fingerprint 80S ribosomes and polysomes from a human neuronal cell line and,Drosophila melanogastercultured cells and ovaries. Specifically, we show that the peak amplitude and dwell time characteristics of 80S ribosomes are distinct from polysomes and can be used to discriminate ribosomes from polysomes in mixed samples. Moreover, we are able to distinguish large polysomes, containing more than 7 ribosomes, from those containing 2-3 ribosomes, and demonstrate a correlation between polysome size and peak amplitude. This study highlights the application of solid-state nanopores as a rapid analytical tool for the detection and characterization of ribosomal complexes.
Integron activity accelerates the evolution of antibiotic resistance
Authors: Souque Célia , Escudero José A. , MacLean R.Craig 
Published: August 2020

AbstractMobile integrons are widespread genetic platforms that allow bacteria to modulate the expression of antibiotic resistance cassettes by shuffling their position from a common promoter. Antibiotic stress induces the expression of an integrase that excises and integrates cassettes, and this unique recombination and expression system is thought to allow bacteria to ‘evolve on demand’ in response to antibiotic pressure. To test this hypothesis, we inserted a custom three cassette integron intoP. aeruginosa, and used experimental evolution to measure the impact of integrase activity on adaptation to gentamicin. Crucially, integrase activity accelerated evolution by increasing the expression of a gentamicin resistance cassette through duplications and by eliminating redundant cassettes. Importantly, we found no evidence of deleterious off-target effects of integrase activity. In summary, integrons accelerate resistance evolution by rapidly generating combinatorial variation in cassette composition while maintaining genomic integrity.
Genome Diversity in Ukraine
Authors: Oleksyk Taras K. , Wolfsberger Walter W. , Weber Alexandra , Shchubelka Khrystyna , Oleksyk Olga T. , Levchuk Olga , Patrus Alla , Lazar Nelya , Castro-Marquez Stephanie O. , Boldyzhar Patricia , Urbanovych Alina , Stakhovska Viktoriya , Malyar Kateryna , Chervyakova Svitlana , Podoroha Olena , Kovalchuk Natalia , Hasynets Yaroslava , Rodriguez-Flores Juan L. , Medley Sarah , Battistuzzi Fabia , Liu Ryan , Hou Yong , Chen Siru , Yang Huanming , Yeager Meredith , Dean Michael , Mills Ryan E. , Smolanka Volodymyr 
Published: August 2020

AbstractThe main goal of this collaborative effort is to provide genome wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for the public data release. DNBSEQ-G50 sequences, and genotypes by an Illumina GWAS chip were cross-validated on multiple samples, and additionally referenced to one sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. The genome data has been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, CNVs, SNPs and microsatellites. This study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for historic and medical research in a large understudied population. While most of the common variation is shared with other European populations, this survey of population variation contributes a number of novel SNPs and structural variants that have not been reported in the gnomAD/1KG databases representing global distribution of genomic variation. These endemic variants will become a valuable resource for designing future population and clinical studies, help address questions about ancestry and admixture, and will fill a missing place in the puzzle characterizing human population diversity in Eastern Europe. Our results indicate that genetic diversity of the Ukrainian population is uniquely shaped by the evolutionary and demographic forces, and cannot be ignored in the future genetic and biomedical studies. This data will contribute a wealth of new information bringing forth different risk and/or protective alleles. The newly discovered low frequency and local variants can be added to the current genotyping arrays for genome wide association studies, clinical trials, and in genome assessment of proliferating cancer cells.