bluuebunny/crossref_metadata_2025 huggingface dataset:
Generative modeling of single-cell population time series for inferring cell differentiation landscapes
Authors: Yeo Grace H.T. , Saksena Sachit D. , Gifford David K.
Published: August 2020

Existing computational methods that use single-cell RNA-sequencing for cell fate prediction either summarize observations of cell states and their couplings without modeling the underlying differentiation process, or are limited in their capacity to model complex differentiation landscapes. Thus, contemporary methods cannot predict how cells evolve stochastically and in physical time from an arbitrary starting expression state, nor can they model the cell fate consequences of gene expression perturbations. We introduce PRESCIENT (Potential eneRgy undErlying Single Cell gradIENTs), a generative modeling framework that learns an underlying differentiation landscape from single-cell time-series gene expression data. Our generative model framework provides insight into the process of differentiation and can simulate differentiation trajectories for arbitrary gene expression progenitor states. We validate our method on a recently published experimental lineage tracing dataset that provides observed trajectories. We show that this model is able to predict the fate biases of progenitor cells in neutrophil/macrophage lineages when accounting for cell proliferation, improving upon the best-performing existing method. We also show how a model can predict trajectories for cells not found in the model’s training set, including cells in which genes or sets of genes have been perturbed. PRESCIENT is able to accommodate complex perturbations of multiple genes, at different time points and from different starting cell populations. PRESCIENT models are able to recover the expected effects of known modulators of cell fate in hematopoiesis and pancreatic β cell differentiation.
Process-based model of fish incubation survival for designing reservoir operations: a case study for Sacramento River winter-run Chinook salmon
Authors: Anderson James J. , Beer W. Nicholas , Israel Joshua A. , Greene Sheila
Published: August 2020

Allocating reservoir flows to meet societal and ecosystem needs under increasing demands for water and increasing climatic variability presents challenges to resource managers. Often, regulated rivers have been operated to meet flow and temperature compliance points that mimic historical patterns. Because it is difficult to assess if this approach is efficient or equitable, new more process-based approaches to regulation are being advanced. This paper describes such an approach with a model of egg incubation survival of Sacramento River winter-run Chinook salmon (SRWRC,Oncorhynchus tshawytscha). Thermal mortality only occurs in a critical window around egg hatching when the embryo is most sensitive to temperature stress. The duration of the critical window has significant implications for Shasta Reservoir operations that are designed to control temperature during SRWRC incubation. Previous operations sought to maintain a low temperature over the entire incubation period. However, model analysis suggests that targeting cold water directly to the critical egg hatching stage provides higher survival while requiring less cold water resources. The calibrated model is publicly accessible through a web interface connected to real-time river and fish databases and a river temperature forecast model. The system is an example of the next step of river management that integrates databases with hydrological and process-based biological models for real-time analysis and for forecasting effects of river operations on the environment.
Mapping ribonucleotides embedded in genomic DNA to single-nucleotide resolution using Ribose-Map
Authors: Gombolay Alli L. , Storici Francesca
Published: August 2020

Ribose-Map is a user-friendly, standardized bioinformatics toolkit for the comprehensive analysis of ribonucleotide sequencing experiments. It allows researchers to map the locations of ribonucleotides in DNA to single-nucleotide resolution and identify biological signatures of ribonucleotide incorporation. In addition, it can be applied to data generated using any currently available high-throughput ribonucleotide sequencing technique, thus standardizing the analysis of ribonucleotide sequencing experiments and allowing direct comparisons of results. This protocol describes in detail how to use Ribose-Map to analyze raw ribonucleotide sequencing data, including preparing the reads for analysis, locating the genomic coordinates of ribonucleotides, exploring the genome-wide distribution of ribonucleotides, determining the nucleotide sequence context of ribonucleotides, and identifying hotspots of ribonucleotide incorporation. Ribose-Map does not require background knowledge of ribonucleotide sequencing analysis and assumes only basic command-line skills. The protocol requires less than 3 hr of computing time for most datasets and about 30 min of hands-on time.
European agroforestry is no universal remedy for biodiversity: a time-cumulative meta-analysis
Authors: Mupepele Anne-Christine , Keller Matteo , Dormann Carsten F
Published: August 2020

Background

Agroforestry is a production system combining trees with crops or livestock. It has the potential to increase biodiversity in relation to single-use systems, such as pastures or conventional agriculture, by providing a higher habitat heterogeneity. In a literature review and subsequent meta-analysis, we investigated the relationship between biodiversity and agroforestry and critically appraise the underlying evidence of the results.

Results

Biodiversity in agroforestry was higher than in conventional agriculture, but could not outcompete pastures, forests and abandoned agroforestry systems. There was no overall biodiversity benefit in agroforestry systems. Data were available for plants, birds, bats and arthropods. Arthropods and birds were the two taxonomic groups profiting from agroforestry systems. A time-cumulative meta-analysis shows that there was no general benefit of biodiversity at any point in the past besides in early 2015. Time-cumulative meta-analysis can unravel missing robustness of meta-analytical results if conclusions alternate between significant to non-significant summary effect sizes over time.

Conclusion

Agroforestry increases biodiversity only in silvoarable systems compared with conventional agriculture. But even this result is based on a small magnitude and single-study effect sizes were heterogeneous with sometimes opposing conclusions. The latter suggests the importance of other usually unmeasured variables, such as landscape parameters or land-use history, influencing biodiversity in agroforestry systems.
A targetable epigenetic vulnerability in PI3K/AKT inhibitor resistant cancers
Authors: Wu Di , Yan Yuqian , Wei Ting , Ye Zhenqing , Xiao Yutian , Pan Yunqian , Orme Jacob J. , Wang Dejie , Wang Liguo , Ren Shancheng , Huang Haojie
Published: August 2020

Acquisition of resistance to PI3K/AKT-targeted monotherapy implies the existence of common resistance mechanisms independent of cancer type. Here we demonstrate that PI3K/AKT inhibitors cause glycolytic crisis, acetyl-CoA shortage and a global decrease in histone acetylation. Also, PI3K/AKT inhibitors induce drug resistance by selectively augmenting H3K27 acetylation and binding of CBP/p300 and BRD4 proteins at a subset of growth factor and receptor (GF/R) gene loci. BRD4 occupation at these loci and drug resistant cell growth are vulnerable to both bromodomain and HDAC inhibitors. Little or none occupation of HDAC proteins at the GF/R gene loci underscores the paradox that cells respond equivalently to the two classes of inhibitors with opposite modes of action. Targeting this unique epigenetic vulnerability offers two viable strategies to overcome PI3K/AKT inhibitor resistance in different cancers.
In vivoRyR1 reduction in muscle triggers a core-like myopathy
Authors: Pelletier Laurent , Petiot Anne , Brocard Julie , Giannesini Benoit , Giovannini Diane , Sanchez Colline , Travard Lauriane , Chivet Mathilde , Beaufils Mathilde , Kutchukian Candice , Bendahan David , Metzger Daniel , Armstrong Clara Franzini , Romero Norma B. , Rendu John , Jacquemond Vincent , Fauré Julien , Marty Isabelle
Published: August 2020

Some mutations in theRYR1gene lead to congenital myopathies, through reduction in this calcium channel expression level, but the functional whole organism consequences of reduction in RyR1 amount have never been studied. We have developed and characterized a mouse model with inducible muscle specificRYR1deletion. Recombination in theRYR1gene resulted in a progressive reduction in the protein amount and was associated with a progressive muscle weakness and atrophy. Calcium fluxes in isolated muscle fibers were accordingly reduced. Alterations in the muscle structure were observed, with fibers atrophy, abnormal mitochondria distribution, membrane remodeling, associated with increase in the expression level of many proteins and inhibition of the autophagy process. This model demonstrates that RyR1 reduction is sufficient to recapitulate most features of Central Core Disease, and accordingly similar alterations were observed in muscle biopsies from Central Core Disease patients, pointing to common pathophysiological mechanisms related to RyR1 reduction.
Experimental pieces of evidence forMycobacterium ulceransdormancy
Authors: Loukil A. , Lalaoui R. , Bogreau H. , Regoui S. , Drancourt M. , Hammoudi N
Published: August 2020

Background

WhetherMycobacterium ulcerans, the etiological agent of the neglected Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely relatedMycobacteriumspecies, is not established.

Methodology

SixM. ulceransstrains were exposed to a progressive depletion in oxygen for two months, using a previously described Wayne model of dormancy; and further examined by microscopy using DDD staining, microcalorimetry and subculture in the presence of dead and replicativeM. ulceransas controls.

Principal Findings/Conclusions

M. ulceransCU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile Red-stained intracellular lipid droplets after DDD staining and a 14-20-day regrowth when exposed to ambient air, diagnosing dormancy. A fifthM. ulcerans19423 strain stained negative in DDD and slowly regrew in 27 days. Three testedM. ulceransstrains yielded microcalorimetric pattern similar to that of the negative (dead) homologous controls, differing from that of the homologous positive (replicative) controls. The relevance of these experimental observations, suggesting a previously unreported dormancy state ofM. ulcerans, needs to be investigated in the natural ecological niches whereM. ulceransthrive and in Buruli ulcer lesions.

Author summary

Mycobacterium ulceransis an environmental opportunistic pathogen of mammals and humans, causing a subcutaneous necrotizing infection named Buruli ulcer. Molecular detection ofM. ulceransDNA revealed different ecological niches whereM. ulceransmay thrive, but the molecular biology approach does not catch the physiological state ofM. ulceransin these different ecological niches. Thus, the reservoir and the mode of transmission ofM. ulceransremain elusive. Here, we investigated experimental dormancy ofM. ulceransby using a previously described Wayne model of dormancy coupled with microscopy using DDD staining, microcalorimetry and subculture. Our findings demonstrate for the first time that someM. ulceransstrains exhibit a physiological state of dormancy; potentially limiting isolation and culture ofM. ulceransfrom environmental niches.
A Validated Functional Analysis of PALB2 Missense Variants for Use in Clinical Variant Interpretation
Authors: Brnich Sarah E. , Arteaga Eyla Cristina , Wang Yueting , Tan Xianming , Berg Jonathan S.
Published: August 2020

Clinical genetic testing readily detects germline genetic variants. Yet, the evidence available for variant classification as benign or pathogenic is often limited by the rarity of individual variants, leading to many “variant of uncertain significance” (VUS) classifications. VUS cannot guide clinical decisions, complicating counseling and management. Laboratory assays can potentially aid reclassification, but require benchmarking against variants with definitive interpretations to have sufficient predictive power for clinical use. Of all clinically identified germline variants in hereditary breast cancer genePALB2(Partner and Localizer of BRCA2), ~50% are VUS and ~90% of VUS are missense. Truncating PALB2 variants have homologous recombination (HR) defects and instead rely on error-prone non-homologous end-joining (NHEJ) for DNA damage repair (DDR). Recent reports show some missense PALB2 variants may also be damaging, but thus far functional studies have lacked benchmarking controls. Using the Traffic Light Reporter (TLR) to quantify cellular HR and NHEJ using fluorescent markers, we assessed variant-level DDR capacity in hereditary breast cancer genes. We first determined the TLR’s dynamic range usingBRCA2missense variants of known significance as benchmarks for normal/abnormal HR function. We then tested 37PALB2variants, generating functional data for germlinePALB2variants at a moderate level of evidence for a pathogenic interpretation (PS3_moderate) for 8 variants, or a supporting level of evidence in favor of a benign interpretation (BS3_supporting) for 13 variants, based on the ability of the assay to correctly classifyPALB2validation controls. This new data can be applied in subsequent variant interpretations for direct clinical benefit.
Anin vitroChondro-osteo-vascular Triphasic Model of the Osteochondral Complex
Authors: Pirosa Alessandro , Gottardi Riccardo , Alexander Peter G. , Puppi Dario , Chiellini Federica , Tuan Rocky S.
Published: August 2020

The generation of engineered models of the osteochondral complex to study its pathologies and develop possible treatments is hindered by the distinctly different properties of articular cartilage and subchondral bone, with the latter characterized by vascularization.In vitromodels of the osteochondral complex have been mainly engineered as biphasic constructs containing just cartilage and bone cells, a condition very dissimilar from thein vivoenvironment. The different cellular components of the osteochondral complex are governed by interacting biochemical signaling; hence, to study the crosstalk among chondrocytes, osteoblasts, and endothelial cells, we have developed a novel triphasic model of the osteochondral tissue interface. Wet-spun poly(ε-caprolactone) (PCL) and PCL/hydroxyapatite (HA) scaffolds in combination with a methacrylated gelatin (gelMA) hydrogel were used as the polymeric backbone of the constructs. The scaffold components were engineered with human bone marrow derived mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs), and differentiated using a dual chamber microphysiological system (MPS) bioreactor that allows the simultaneous, separate flow of media of different compositions for induced differentiation of each compartment towards a cartilaginous or osseous lineage. Within the engineered Microphysiological Vascularized Osteochondral System (microVOCS), hMSCs showed spatially distinct chondrogenic and osteogenic markers in terms of histology and gene expression. HUVECs formed a stable capillary-like network in the engineered bone compartment and enhanced both chondrogenic and osteogenic differentiation of hMSCs, resulting in the generation of anin vitrosystem that mimics a vascularized osteochondral interface tissue.
Systematic Detection of Large-Scale Multi-Gene Horizontal Transfer in Prokaryotes
Authors: Kloub Lina , Gosselin Sean , Fullmer Matthew , Graf Joerg , Gogarten J. Peter , Bansal Mukul S.
Published: August 2020

Horizontal gene transfer (HGT) is central to prokaryotic evolution. However, little is known about the “scale” of individual HGT events. In this work, we introduce the first computational framework to help answer the following fundamental question: How often does more than one gene get horizontally transferred in a single HGT event? Our method, calledHoMer, uses phylogenetic reconciliation to infer single-gene HGT events across a given set of species/strains, employs several techniques to account for inference error and uncertainty, combines that information with gene order information from extant genomes, and uses statistical analysis to identify candidate horizontal multi-gene transfers (HMGTs) in both extant and ancestral species/strains. HoMer is highly scalable and can be easily used to infer HMGTs across hundreds of genomes.

We apply HoMer to a genome-scale dataset of over 22000 gene families from 103Aeromonasgenomes and identify a large number of plausible HMGTs of various scales at both small and large phylogenetic distances. Analysis of these HMGTs reveals interesting relationships between gene function, phylogenetic distance, and frequency of multi-gene transfer. Among other insights, we find that (i) the relative frequency of HMGT increases as divergence between genomes increases, (ii) HMGTs often have conserved gene functions, and (iii) rare genes are frequently acquired through HMGT. We also analyze in detail HMGTs involving the zonula occludens toxin and type III secretion systems. By enabling the systematic inference of HMGTs on a large scale, HoMer will facilitate a more accurate and more complete understanding of HGT and microbial evolution.
The influenza A virus host shutoff factor PA-X is rapidly turned over in a strain-specific manner
Authors: Levene Rachel Emily , Shrestha Shailab D. , Gaglia Marta Maria
Published: August 2020

The influenza A endoribonuclease PA-X regulates virulence and transmission of the virus by reducing host gene expression and thus regulating immune responses to influenza A virus. Despite this key function in viral biology, the levels of PA-X protein remain markedly low during infection, and previous results suggest that these low levels are not solely the result of regulation of the level of translation and RNA stability. How PA-X is regulated post-translationally remains unknown. We now report that the PA-X protein is rapidly turned over. PA-X from multiple viral strains are short-lived, although the half-life of PA-X ranges from ∼30 minutes to ∼3.5 hours depending on the strain. Moreover, sequences in the variable PA-X C-terminal domain are primarily responsible for regulating PA-X half-life, although the N-terminal domain also accounts for some differences among strains. Interestingly, we find that the PA-X from the 2009 pandemic H1N1 strain has a longer half-life compared to the other variants we tested. This PA-X isoform has been reported to have a higher host shutoff activity, suggesting a role for protein turnover in regulating PA-X activity. Collectively, this study reveals a novel regulatory mechanism of PA-X protein levels that may impact host shutoff activity during influenza A virus infection.

IMPORTANCE

The PA-X protein from influenza A virus reduces host immune responses to infection through suppressing host gene expression, including genes encoding the antiviral response. Thus, it plays a central role in influenza A virus biology. Despite its key function, PA-X was only discovered in 2012 and much remains to be learned including how PA-X activity is regulated to promote optimal levels of viral infection. In this study, we reveal that PA-X protein levels are very low likely because of rapid turnover. We show that instability is a conserved property among PA-X variants from different strains of influenza A virus, but that the half-lives of PA-X variants differ. Moreover, the longer half-life of PA-X from the 2009 pandemic H1N1 strain correlates with its reported higher activity. Therefore, PA-X stability may be a way to regulate its activity and may contribute to the differential virulence of influenza A virus strains.
The structure of the Moco carrier protein fromRippkaea orientalis
Authors: Krausze Joern , Hercher Thomas W. , Archna Archna , Kruse Tobias
Published: August 2020

The molybdenum cofactor (Moco) is the prosthetic group of all molybdenum-dependent enzymes except for nitrogenase. The multistep biosynthesis pathway of Moco and its function in molybdenum-dependent enzymes are already well understood. The mechanisms of Moco transfer, storage and insertion, on the other hand, are not. In the cell, Moco is usually not found in its free form and remains bound to proteins because of its sensitivity to oxidation. The green algaChlamydomonas reinhardtiiharbors a Moco carrier protein (MCP) that binds and protects Moco but is devoid of enzymatic function. It has been speculated that this MCP acts as a means of Moco storage and transport. Here, the search for potential MCPs has been extended to the prokaryotes, and many MCPs were found in cyanobacteria. A putative MCP fromRippkaea orientalis(RoMCP) was selected for recombinant production, crystallization and structure determination. RoMCP has a Rossmann-fold topology that is characteristic of nucleotide-binding proteins and a homotetrameric quaternary structure similar to that of the MCP fromC. reinhardtii. In each protomer, a positively charged crevice was identified that accommodates up to three chloride ions, hinting at a potential Moco-binding site. Computational docking experiments supported this notion and gave an impression of the RoMCP–Moco complex.
Crystal structures, Hirshfeld atom refinements and Hirshfeld surface analyses of tris(4,5-dihydrofuran-2-yl)methylsilane and tris(4,5-dihydrofuran-2-yl)phenylsilane
Authors: Krupp Anna , Barth Eva Rebecca , Seymen Rana , Strohmann Carsten
Published: August 2020

The title compounds, C13H18O3Si (1) and C18H20O3Si (2), represent functionalizable dihydrofuranylsilanes, which permit substitution by a variety of nucleophiles. The crystal structures of 1 and 2 display weak intermolecular C—H...O hydrogen-bonding interactions (quantified by Hirshfeld surface analysis), leading to a two-dimensional supramolecular network for 1 and a one-dimensional supramolecular network for 2. The crystal structures of 1 and 2 were refined both on the basis of the independent atom model (IAM) and the Hirshfeld atom refinement (HAR) approach, and the results are comparatively discussed.
Structure of a diorganotelluroxonium(IV) cation, {[2,6-(CH2NMe2)2C6H3Te(μ-O)]2}2+, with the trichlorido(dimethyl sulfoxide)platinum(II) anion
Authors: Gupta Anand , Deka Rajesh , Butcher Ray J. , Singh Harkesh B.
Published: August 2020

In the title salt, di-μ-oxido-bis{2,6-bis[(dimethylamino)methyl]phenyl-κC
1}tellurium(IV) bis[trichlorido(dimethyl sulfoxide-κS)platinate(II)], (C24H38N4O2Te2)[PdCl3(C2H6OS)]2, which crystallizes in the triclinic space group P\overline{1}, each Te atom is in a distorted five-coordinated TeO2N2C square-pyramidal geometry (τ values of 0.026 and 0.001) with the C atoms of the phenyl rings occupying the apical positions. The phenyl rings in the [C24H38N4O2Te2]2+ cation are in a cis arrangement to enable this species to participate in Te...Cl cation–anion interactions. There are also C—H...O interactions involving the dimethyl sulfoxide ligands and numerous cation–anion and anion–anion C—H...Cl interactions, which link the ions into a complex three-dimensional array.
Analyzing the barriers to implementation of mass customization in Indian SMEs using integrated ISM-MICMAC and SEM
Authors: Ullah Inayat , Narain Rakesh
Published: August 2020

Purpose

The purpose of this research is to identify the crucial barriers to the implementation of mass customization (MC) in Indian SMEs and to investigate the interactions among them so that important managerial implications could be formulated to facilitate the implementation of MC in SMEs.

Design/methodology/approach

The contextual relationships and hierarchies of the barriers are established through the interpretive structural modelling (ISM) approach, and MICMAC analysis has been used to classify the barriers into different groups. Further, structural equation modelling based on partial least squares (PLS-SEM) has been applied to statistically validate the ISM model using the data collected through a questionnaire-based survey of Indian organizations.

Findings

A portfolio of barriers, containing 16 items, has been identified from the literature review and a series of semi-structured interviews of practitioners. The study develops a structural model by establishing relationships and imposing directions among the barriers and classifies the barriers according to their driving and dependence power to serve as a roadmap for SMEs willing to implement MC into practice.

Practical implications

The study highlights the critical barriers which have a significant impact on other barriers and need to be handled at priority. Also, the present research renders insights to SMEs to better prioritize their efforts and resources to overcome these barriers.

Originality/value

This research happens to be first in the MC literature that investigates the key barriers responsible for hindering the implementation of MC in SMEs and develops a statistically validated contextual model showing hierarchies and relationships of the barriers.
Remarkable lives. Lizzie Hehir in conversation with Jerome Carson
Authors: Hehir Lizzie , Carson Jerome
Published: August 2020

Purpose

The purpose of this paper is to provide a profile of Lizzie Hehir. Lizzie tells her own story and is then interviewed by Jerome.

Design/methodology/approach

This series of papers used the case study approach. However, each paper is written collaboratively, using the person’s own words. The deeply individual nature of each person’s story reminds us of the complexities of working in mental health.

Findings

In her account, Lizzie tells us of her long-term battles with self-harm. It was a struggle that she eventually won.

Research limitations/implications

Individual stories allow us to access people’s lived experience with mental illness. No diagnostic manual can ever truly categorise this uniqueness.

Practical implications

Lizzie shows it is possible to overcome self-harm though she still experiences something of the trauma she went through when she has triggers.

Social implications

When we see burns victims, we seldom approach them asking them how they sustained their injuries, but as Lizzie points out, many people feel able to ask people who have self-harmed about their injuries.

Originality/value

Lizzie writes with conviction and humility. Now working in mental health, she is able to reach out to others who are as troubled as she once was.
Species coexist more easily if reinforcement is based on habitat preferences than on species recognition
Authors: Kyogoku Daisuke , Kokko Hanna
Published: August 2020

Maladaptive hybridization selects for prezygotic isolation, a process known as reinforcement. Reinforcement reduces gene flow and contributes to the final stage of speciation. Ecologically, however, coexistence of the incipient species is difficult if they initially use identical resources.

Habitat segregation offers an alternative to species discrimination as a way to reduce gene flow: production of unfit hybrids is reduced if mate encounters become rare due to differing habitat choice. Using a modelling approach, we show that hybridization avoidance alone can select for habitat specialization, even if neither of the species is intrinsically better at using a specific niche.

While habitat segregation and species discrimination both reduce the risk of producing unfit hybrids, these two isolation mechanisms differ from each other with respect to their effects on resource competition. Our model shows that, as a consequence of such differences, reinforcement evolves much more easily if hybridization is avoided based on habitat segregation than if the mechanism involves species recognition (mate choice traits).

We also examine the outcomes when both isolation mechanisms evolve jointly. The establishment of one isolation mechanism a priori weakens selection for the other. However, an asymmetry persists here too. The net effect of habitat segregation on species discrimination was typically facilitative, but not vice versa. This asymmetry arises because habitat segregation, by enhancing coexistence, secures time for the subsequent evolution of species discrimination in a mate choice context (still relevant if habitat use is not perfectly segregated). Species discrimination does not have such a stabilizing effect on coexistence.

Our results emphasize the importance of habitat segregation in reinforcement and offer a way to interpret findings where closely related taxa show similar performance on different resources or in different habitats. Studies of ecological generalization and specialization should therefore take into account that niche differences can be initiated and/or maintained by hybridization avoidance.
Soil organic carbon accumulation modes between pioneer and old‐growth forest ecosystems
Authors: Xiong Xin , Zhou Guoyi , Zhang Deqiang
Published: August 2020

Increasing evidence suggests that high biomass and litterfall do not necessarily bring about soil organic carbon (SOC) sinks, contrary to the assumption that higher litterfall implies higher SOC when designing carbon models. The underlying mechanism is related to the quality of litter.

We conducted 15 years (2000–2015) of consecutive field measurements of δ13C values in SOC and plants in a pioneer forest (Pinus massoniana forest, PF) and an old‐growth forest (monsoon evergreen broadleaved forest, BF), using an isotope mixing model based on mass balance to quantify the effects of vegetation on SOC stock and soil characteristics.

The carbon to nitrogen (C/N) ratio of litter in BF was lower than that in PF. The proportion of organic carbon yield input to the soil (Cinput) to the total litter carbon loss during decomposition was 38.7 ± 3.3% and 28.0 ± 2.1% in BF and PF respectively. New carbon input was higher in BF (148.7 ± 8.8 g C m−2 year−1) than PF (99.7 ± 4.5 g C m−2 year−1), though there was a non‐significant difference in annual litterfall between the two forests. Moreover, the Cinput was concentrated in the topsoil layer in PF but distributed in a more dispersed state across the whole soil profile in BF. Consequently, only the δ13C values of SOC decreased in the topsoil layer of PF, whereas these decreased at both soil depths in BF from 2000 to 2015.

Compared with PF, BF exhibited higher carbon input and a more favourable soil environment for carbon storage. It was the amount of intermediate product (i.e. Cinput) of litter decomposition, not the amount of litterfall itself, that drove the contrasting differences in SOC status.

Synthesis and applications. Litter quality controls soil organic carbon (SOC) accumulation by regulating the fate of decomposing litter, which may explain why old‐growth forests can sustainably accumulate carbon in soil. This finding questions the carbon models that predict the dependence of SOC accumulation on biomass and litter yield and suggests that litter quality should be valued in future carbon cycling models.
Continuation and replacement of Vibrio cholerae non‐O1 clonal genomic groups isolated from Plecoglossus altivelis fish in freshwaters
Authors: Kawai Mikihiko , Ota Atsushi , Takemura Taichiro , Nakai Toshihiro , Maruyama Fumito
Published: August 2020

The dissemination and abundances of Vibrio species in aquatic environments are of interest, as some species cause emerging diseases in humans and in aquatic organisms like fish. It is suggested that Vibrio cholerae non‐O1 infections of Plecoglossus altivelis (‘ayu’) were spread to various parts of Japan through the annual transplantation of juvenile fish. To investigate this, we used genome‐aided tracing of 17 V. cholerae strains isolated from ayu between the 1970s and 1990s in different Japanese freshwater systems. The strains formed a genomic clade distinct from all known clades, which we designate as the Ayu clade. Two clonal genomic groups identified within the clade, Ayu‐1 and Ayu‐2, persisted for a few years (between 1977 to 1979 and 1987 to 1990, respectively), and clonal replacement of Ayu‐1 by Ayu‐2 took place over an 8‐year period. Despite the high similarity between Ayu‐1 and Ayu‐2 (> 99.9% identity and > 97% fraction of genomes shared), differences in their gene repertoires were found, raising the possibility that they are phenotypically distinct. These results highlight the importance of genome‐based studies for understanding the long‐term dynamics of populations over the timescale of years.
Is lactate lower in septic patients who are prescribed beta blockers? Retrospective cohort study of an intensive care population
Authors: Pham Diem , Ward Harrison , Yong Brian , Mahendra Raj Jayanand , Awad Mariam , Harvey Martyn , Doherty Steven , Cave Grant
Published: August 2020

Objective

Elevated serum lactate has long been considered an important marker of sepsis severity. Increasing evidence supports catecholamine‐stimulated aerobic glycolysis being a major contributor to the hyperlactataemia seen in sepsis. Beta‐blockade may blunt such catecholamine mediated rise in lactate analogous to the way it can mask tachycardia. This could impact the way we evaluate sepsis severity and adequacy of initial treatment. The objective of this study is to investigate whether septic patients who were on beta‐blocker treatment at presentation have lower serum lactate level.

Methods

Using a retrospective cohort design we gathered data on patients admitted to our base hospital intensive care unit with APACHE III diagnosis of sepsis and septic shock during the 2017 calendar year. Serum lactate, current medications, presenting vital signs, illness severity scores, laboratory data and mortality outcome were extracted from patients' medical record and the unit's clinical database.

Results

Of 189 records analysed, 49 patients were concurrently prescribed beta‐blockers. More beta‐blocked patients were male, beta‐blocked patients were older, and a greater proportion of beta blocked patients had their first lactate measured as an inpatient. After regression to correct for identified significant covariates mean serum lactate was 0.87 (95% confidence interval 0.05–1.69) mmol/L lower in those prescribed beta blockers.

Conclusions

In our cohort pre‐existing beta blocker treatment was associated with lower serum lactate measurements in patients presenting with sepsis. Pre‐existing beta blocker treatment may reduce serum lactate at presentation in patients with sepsis.
To intubate or not to intubate? Predictors of inhalation injury in burn‐injured patients before arrival at the burn centre
Authors: Dyson Kylie , Baker Paul , Garcia Nicole , Braun Anna , Aung Myat , Pilcher David , Smith Karen , Cleland Heather , Gabbe Belinda
Published: August 2020

Objective

Inhalation injury occurs in approximately 10–20% of burn patients and is associated with increased mortality. There is no clear method of identifying patients at risk of inhalation injury or requiring intubation in the pre‐hospital setting. Our objective was to identify pre‐burn centre factors associated with inhalation injury confirmed on bronchoscopy, and to develop a prognostic model for inhalation injury.

Methods

We analysed acute admissions from the Victorian Adult Burns Service and Ambulance Victoria electronic patient care records for 1 July 2009 to 30 June 2016. We defined inhalation injury as an Abbreviated Injury Scale of >1 on bronchoscopy. A multivariable logistic regression prediction model was developed based on pre‐burn centre factors.

Results

Emergency medical services transported 1148 patients who were admitted to the burn centre. The median age of patients was 39 years and most patients had <10% total body surface area (%TBSA) burned. The prevalence of confirmed inhalation injury was 11%. Increasing %TBSA burned, flame, enclosed space, face burns, hoarse voice, soot in mouth and shortness of breath were predictive of inhalation injury. The model provided excellent discrimination (area under curve 0.87, 95% confidence interval 0.84–0.91). A lower proportion of patients intubated at a non‐burn centre had an inhalation injury (33%) compared to patients intubated by emergency medical services (54%) and in the burn centre (58%).

Conclusions

A model to predict inhalation injury in burn‐injured patients was developed with excellent discrimination. This model requires prospective testing but could form an integral part of clinician decision‐making.
Workplace violence in emergency departments: The health professionals and security personnel alliance
Authors: Ramacciati Nicola , Giusti Gian Domenico
Published: August 2020

Violence in the health sector is a widespread worldwide phenomenon. Emergency nurses and emergency physicians are among the most exposed. In violent incidents, security personnel also play an important role. Wand and colleagues on Emergency Medicine Australasia have tried to give voice to the opinions and experiences of security personnel in responding to aggression and behavioural problems. Sharing some data from our 2016 Italian National Survey on Violence towards Emergency Nurses, further elements are provided on this issue. The different perspectives of healthcare professionals and security personnel can converge in an alliance to counteract violence in the ED.
Chromosome‐level de novo genome assembly of Sarcophaga peregrina provides insights into the evolutionary adaptation of flesh flies
Authors: Ren Lipin , Shang Yanjie , Yang Li , Wang Shiwen , Wang Xiang , Chen Shan , Bao Zhigui , An Dong , Meng Fanming , Cai Jifeng , Guo Yadong
Published: August 2020

Sarcophaga peregrina is considered to be of great ecological, medical and forensic significance, and has unusual biological characteristics such as an ovoviviparous reproductive pattern and adaptation to feed on carrion. The availability of a high‐quality genome will help to further reveal the mechanisms underlying these charcateristics. Here we present a de novo‐assembled genome at chromosome scale for S. peregrina. The final assembled genome was 560.31 Mb with contig N50 of 3.84 Mb. Hi‐C scaffolding reliably anchored six pseudochromosomes, accounting for 97.76% of the assembled genome. Moreover, 45.70% of repeat elements were identified in the genome. A total of 14,476 protein‐coding genes were functionally annotated, accounting for 92.14% of all predicted genes. Phylogenetic analysis indicated that S. peregrina and S. bullata diverged ~ 7.14 million years ago. Comparative genomic analysis revealed expanded and positively selected genes related to biological features that aid in clarifying its ovoviviparous reproduction and carrion‐feeding adaptations, such as lipid metabolism, olfactory receptor activity, antioxidant enzymes, proteolysis and serine‐type endopeptidase activity. Protein‐coding genes associated with ovoviparity, such as yolk proteins, transferrin and acid sphingomyelinase, were identified. This study provides a valuable genomic resource for S. peregrina, and sheds insight into further revealing the underlying molecular mechanisms of adaptive evolution.
A systematic review of internet‐based information on dermatomyositis and polymyositis
Authors: Haque Ashraful , Cox Miriam , Sandler Robert D. , Hughes Michael
Published: August 2020

Aim

Patients with rheumatic diseases are increasingly using internet‐based information to inform healthcare utilization and make treatment decisions. Our aim was to assess the readability and quality of internet‐based information on dermatomyositis (DM) and polymyositis (PM).

Method

Key words “Dermatomyositis” and “Polymyositis” were searched on 3 commonly used search engines (Google, Yahoo and Bing). The first 3 pages (~30) of search results were examined from each search engine. Readability of information was assessed using 4 readability formulae (Flesch Reading Ease Score, Flesch‐Kincaid Grade Level, the Simplified Measure of Gobbledygook index, the Coleman‐Liau index). Quality of information was assessed using the DISCERN tool, Journal of The American Medical Association (JAMA) benchmark criteria and Health on The Net Code (HoN code). We also examined Google Trends® data to determine if there were obvious temporal search patterns.

Results

Thirty‐two websites were included in the study after duplicates were removed and exclusion criteria were applied. The overall quality was low including DISCERN with a median overall score of 38/80 (interquartile range 12.25), only 4/32 (13%) websites fulfilled all 4 JAMA benchmark criteria, and 9/32 (28%) had HoN code. Readability of information was assessed using 4 readability formulae (Flesch Reading Ease Score, Flesch‐Kincaid Grade Level, the Simplified Measure of Gobbledygook index, the Coleman‐Liau index. There was no obvious temporal trend in searches on analysis of Google Trends® data.

Conclusion

The overall quality and readability of internet‐based information relating to DM and PM is poor. Patients require appropriate information of high quality and readability throughout the course of their disease in order to make informed decisions on their condition including treatment.
High‐grade myofibroblastic sarcoma of the pleura: A case report and literature review
Authors: Zhao Ruizhi , Wang Jianyang , Zhang Hongtu , Chi Yihebali , Bi Nan
Published: August 2020

High‐grade myofibroblastic sarcoma (HGMS) is a rare cancer that has high recurrence and metastatic rates. Here, we report the first case of HGMS originating from the pleura. Based on the findings of pleural biopsy, pathological examination and immunohistochemical staining, grade III myofibroblastic sarcoma (MS) was diagnosed. The patient underwent eight cycles of chemotherapy (epirubicin and ifosfamide), followed by radiotherapy. As of May 2020, the patient had been followed for six months and no tumor progression had occurred.

Key points

This is the first report of high‐grade myofibroblastic sarcoma originating from the pleura. The patient was treated via nonsurgical strategies, including chemotherapy and radiotherapy.
Dominant atopy risk mutations identified by mouse forward genetic analysis
Authors: SoRelle Jeffrey A. , Chen Zhe , Wang Jianhui , Yue Tao , Choi Jin Huk , Wang Kuan‐wen , Zhong Xue , Hildebrand Sara , Russell Jamie , Scott Lindsay , Xu Darui , Zhan Xiaowei , Bu Chun Hui , Wang Tao , Choi Mihwa , Tang Miao , Ludwig Sara , Zhan Xiaoming , Li Xiaohong , Moresco Eva Marie Y. , Beutler Bruce
Published: August 2020

Background

Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice.

Methods

We screened mice carrying homozygous and heterozygous N‐ethyl‐N‐nitrosourea (ENU)–induced germline mutations for aberrant antigen‐specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation.

Results

Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain‐specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B‐cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss‐of‐function mutations in nine of the 12 genes limiting the IgE response were dominant or semi‐dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations.

Conclusions

Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.
Associations of novel inflammatory markers with long‐term outcomes and recurrence of diverticulitis
Authors: Zager Yaniv , Horesh Nir , Dan Assaf , Aharoni Mor , Khalilieh Saed , Cordoba Mordehay , Nevler Avinoam , Gutman Mordechai , Rosin Danny
Published: August 2020

Background

The neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) have emerged as markers of various outcomes of inflammatory and malignant diseases. The association of those markers with short‐term outcomes of acute diverticulitis has been discussed in recent studies. This study aimed at evaluation of the association of NLR and PLR with long‐term outcomes in patients presenting with acute diverticulitis.

Methods

A retrospective single institute study included patients admitted with acute diverticulitis between 2012 and 2016. Associations were analysed of NLR and PLR values at admission with patient outcomes.

Results

A total of 456 patients were included in the study. High NLR and PLR values were associated with complicated disease (P < 0.01 for both). Among patients with complicated diverticulitis, for those with high NLR, the interval to a recurrent episode of acute diverticulitis was shorter (68.3 days versus 83.7 days, P = 0.044). Patients with high NLR had higher mean number of readmissions (0.54 versus 0.34, P = 0.035). High NLR (10.06 ± 11.23 versus 7.6 ± 8.04, P = 0.012) and PLR (9.64 days ±10.56 versus 7.47 days ±8.225, P = 0.018) were associated with longer cumulative hospital stay due to acute diverticulitis.

Conclusions

High NLR and PLR values were associated with recurrence in acute diverticulitis in terms of shorter interval between recurrent episodes and longer cumulative hospitalization days.
Cytokines in abdominal exudate and serum predict small bowel obstruction following appendectomy
Authors: Ding Hui , Li Hongbo , Yu Hualong , Zhang Wenwei , Li Siyuan
Published: August 2020

Background

This study aimed to investigate the value of inflammatory markers for the prediction of small bowel obstruction (SBO) following appendectomy.

Methods

We included cases of acute appendicitis that underwent laparoscopic appendectomy (LA) in the Qingdao Municipal Hospital between January 2017 and January 2019. The cases were divided into an SBO group and a non‐SBO group depending on whether patients had or did not have SBO, and patients were followed up for at least 1 year. The levels of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐alpha (TNF‐α) in abdominal exudate and venous blood were examined using enzyme‐linked immunosorbent assay.

Results

After 1 year of follow‐up, there were 985 cases in the non‐SBO group and 16 cases in the SBO group. The levels of IL‐1β, IL‐6 and TNF‐α in abdominal exudate on post‐operative day 1 in the SBO group were 172.5 ± 14.7, 2167.3 ± 372.1 and 253.9 ± 12.9 pg/mL, respectively, which were significantly higher than that in the non‐SBO group. The serum levels of IL‐1β, IL‐6, TNF‐α and C‐reactive protein (CRP) in the SBO group were significantly higher than that in the non‐SBO group before surgery. Post‐operatively, the inflammatory markers above decreased significantly and became similar with time in both groups. The logistic regression showed that the levels of peritoneal IL‐6, preoperative serum CRP and perforated appendicitis were significant risk factors of SBO. The specificity and sensitivity of peritoneal IL‐6 were 0.81 and 0.921, respectively.

Conclusion

The IL‐1β, IL‐6, TNF‐α and CRP in serum and abdominal exudate played an important role in SBO after LA. The peritoneal IL‐6 was the most reliable prediction marker for SBO.