bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desmoid fibromatosis in the foot
Authors: Liu Qinqin , Fang Lu , Li Bo 
Published: October 2018

Abstract

Rationale:
Desmoid fibromatosis is a rare benign neoplasm arising from musculoaponeurotic structures with the potential to infiltrate local tissues and recur locally. While the commonly affected regions are the shoulder, chest wall and back, thigh, head and neck, localization in the foot is rare and only a few cases have been reported. Deep-seated lesions of foot tend to spread along the fascia and nerve or tendon sheaths.

Patient concerns:
We present a case of a 41-year-old female with a 3 years history of a slowly enlarging painful mass in the right foot.

Diagnoses:
Desmoid fibromatosis was diagnosed based on clinical manifestations, imaging findings and pathological examinations.

Interventions:
The patient was treated by local incomplete resection.

Outcomes:
The patient recovered well postoperatively and was well followed up at our outpatient department with no evidence of recurrence during 16 months of follow-up after local excision.

Lessons:
Surgical excision is recommended for symptomatic lesions located in the foot. However, it is difficult to excise thoroughly and periodic follow-up is needed to monitor for recurrence. Further study is warranted to determine whether patients benefit more from function preservation instead of complete resection.
Short article: Hepatitis C and G virus coinfection in Punjab, Pakistan: incidence and its correlation analysis with clinical data
Authors: Shahid Muhammad , Idrees Muhammad , Butt Azeem M. , Raza Syed M. , Amin Iram , Rasul Afza , Afzal Samia , Zahid Sadia , Nawaz Rabia 
Published: October 2018

Introduction
Hepatitis G virus (HGV) infection appears to be common in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to investigate the prevalence of HCV/HGV in patients with chronic hepatitis C (CHC) in Pakistan and to look for possible associations with various clinical and histopathological changes in HCV/HGV coinfection and HCV infection.

Patients and methods
The present study included 136 patients. Clinical, biochemical, virological and histological findings were compared between patients coinfected with HCV/HGV and patients with HCV alone.

Results
Of the 136 patients with CHC, 16 (11.76%) were coinfected with HCV/HGV. The mean age of coinfected patients was lower than in patients with HCV alone. HCV/HGV coinfected patients did not show significant differences in sex, clinical presentation, biochemical markers, and liver fibrosis as compared to those with HCV infection. Only the mean values of platelets count, mean corpuscular hemoglobin (MCH), and MCH concentration markers were significantly different in HCV/HGV coinfected patients as compare to patients with HCV alone.

Conclusion
It was found that 11.76% of patients with CHC in Pakistan were associated with HCV/HGV coinfection. No significant differences were observed in clinical and histological features except for platelets count, MCH, and MCH concentration markers between HCV and HGV coinfected patients in comparison with HCV-infected patients.
Comprehensive assessment of multiple biases in small RNA sequencing reveals significant differences in the performance of widely used methods
Authors: Wright Carrie , Rajpurohit Anandita , Burke Emily E. , Williams Courtney , Collado-Torres Leonardo , Kimos Martha , Brandon Nicholas J. , Cross Alan J. , Jaffe Andrew E. , Weinberger Daniel R. , Shin Joo Heon 
Published: October 2018

ABSTRACTHigh-throughput sequencing offers advantages over other quantification methods for microRNA (miRNA), yet numerous biases make reliable quantification challenging. Previous evaluations of the biases associated with small RNA sequencing have focused on adapter ligation bias with limited evaluation of reverse transcription or amplification biases. Furthermore, evaluations of the accuracy of quantifications of isomiRs (miRNA isoforms) or the influence of starting amount on performance have been very limited and no study has yet evaluated differences in the quantification of isomiRs of altered length. In addition, no studies have yet compared the consistency of results derived from multiple moderate starting inputs. We therefore evaluated quantifications of miRNA and isomiRs using four library preparation kits, with various starting amounts, as well as quantifications following removal of duplicate reads using unique molecular identifiers (UMIs) to mitigate reverse transcription and amplification biases. All methods resulted in false isomiR detection; however, the adapter-free method tested was especially prone to false isomiR detection. We demonstrate that using UMIs improves accuracy and we provide a guide for input amounts to improve consistency. Our data show differences and limitations of current methods, thus raising concerns about the validity of quantification of miRNA and isomiRs across studies. We advocate for the use of UMIs to improve accuracy and reliability of miRNA quantifications.
Outpatient prescribing of four major antibiotic classes and prevalence of antimicrobial resistance in US adults
Authors: Goldstein Edward , MacFadden Derek R. , Lee Robyn S. , Lipsitch Marc 
Published: October 2018

AbstractBackgroundThere is limited information on the relation between antibiotic use and antibiotic resistance in the US.MethodsWe used multivariable logistic regression to relate state-specific rates of outpatient prescribing overall for fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011-2014 to state-specific prevalence of resistance for select combinations of antibiotics/bacteria among catheter-associated urinary tract infections (CAUTIs) in the CDC Patient Safety Atlas data between 2011-2014 for adults aged 65+y and 19-64y, adjusting for potential confounders.ResultsRates of fluoroquinolone prescribing were positively associated with prevalence of fluoroquinolone resistance in Escherichia coli and Pseudomonas aeruginosa (both age groups), resistance to extended-spectrum (ES) cephalosporins in E. coli (aged 19-64y), and resistance to methicillin in Staphylococcus aureus (aged 19-64y). Rates of penicillin prescribing were positively associated with prevalence of resistance to fluoroquinolones in E. coli (aged 65+) and P. aeruginosa (both age groups), and resistance to ES cephalosporins in Klebsiella spp. (both age groups). Rates of cephalosporin prescribing were negatively associated with prevalence of resistance to fluoroquinolones in E. coli and resistance to ES cephalosporins in Klebsiella spp. (both age groups). Average annual temperature was positively associated with prevalence of resistance to ES cephalosporins in E. coli and P. aeruginosa, and resistance to fluoroquinolones in E. coli.ConclusionsOur results suggest that prescribing of fluoroquinolones and penicillins to US adults is associated with prevalence of antibiotic resistance, including ESBLs and MRSA. Further work is needed to understand the potential benefit of replacing fluoroquinolones and penicillins by other antibiotics for reducing prevalence of antibiotic resistance.
Resolving Tumour Clonal Heterogeneity and Spatial Complexity using Nuclear Tandem Epitope Protein (nTEP) Barcoding
Authors: Gill Michael B. , Koplev Simon , Machel Anne C. , Miller Martin L. 
Published: October 2018

ABSTRACTTumours are composed of an array of unique cancer cell clones along with many non-tumour cells such as immune cells, fibroblasts and endothelial cells, which make up the complex tumour microenvironment. To better understand the co-evolution of tumour clones and cells of the tumour microenvironment, we require tools to spatially resolve heterotypic cellular interactions at the single cell level. We present a novel protein-based barcoding technology termed nuclear tandem epitope protein (nTEP) barcoding, which can be designed to combinatorially encode and track dozens to hundreds of tumour clones in their spatial context within complex cellular mixtures using multiplexed antibody-based imaging. Here we provide proof-of-principle of nTEP barcoding and develop the technology, which relies on lentiviral - based stable expression of a nuclear-localised fluorophore that contains unique combinations of protein epitope tags that can be decoded by a limited set of antibodies. By generating a series of cell lines expressing unique nTEP barcodes, we were able to robustly identify and spatially deconvolve specific clones present within highly complex cell mixtures at the single cell level using state-of-the-art iterative indirect immunofluorescence imaging (4i). We define the utility of nTEP-barcoding as a powerful tool for visualising and resolving tumour heterogeneity at the cellular level, and envision its usage in mouse tumour models for understanding how tumour clones modulate and interact with stromal- and immune cells in cancer.
A stochastic model of corneal epithelium maintenance and recovery following perturbation
Authors: Moraki E. , Grima R. , Painter K. J. 
Published: October 2018

AbstractVarious biological studies suggest that the corneal epithelium is maintained by active stem cells located in the limbus, the so-called Limbal Epithelial Stem Cell (LESC) hypothesis. While numerous mathematical models have been developed to describe corneal epithelium wound healing, only a few have explored the process of corneal epithelium homeostasis. In this paper we present a purposefully simple stochastic mathematical model based on a chemical master equation approach, with the aim of clarifying the main factors involved in the maintenance process. Model analysis provides a set of constraints on the numbers of stem cells, division rates, and the number of division cycles required to maintain a healthy corneal epithelium. In addition, our stochastic analysis reveals noise reduction as the epithelium approaches its homeostatic state, indicating robustness to noise. Finally, recovery is analysed in the context of perturbation scenarios.
A human impact metric for coastal ecosystems with application to seagrass beds in Atlantic Canada
Authors: Murphy Grace E.P. , Wong Melisa , Lotze Heike K. 
Published: October 2018

AbstractCoastal biogenic habitats are particularly vulnerable to cumulative human impacts from both terrestrial and marine realms. Yet the broad spatial scale used in current global or regional approaches of quantifying multiple anthropogenic stressors are not relevant to the local or bay-wide scales affecting most coastal biogenic habitats. To fill this gap, we developed a standardized human impact metric to quantify the magnitude of anthropogenic impacts to coastal ecosystems more broadly, and biogenic habitats in particular. We applied this metric to 180 seagrass beds (Zostera marina), an important biogenic habitat prioritized for marine protection, across Atlantic Canada. Our impact metric includes five bay-scale and four local-scale terrestrial and marine-based impacts. Results show that seagrass beds and coastal bays in Atlantic Canada exist across a wide gradient of human impacts. Considerable differences in the range and intensity of impacts within and between regions provide insight into where coastal bays and seagrass ecosystems are expected to be most and least affected by individual or cumulative human threats. We discuss implications for management and conservation planning, and the general application of our impact metric to other coastal regions and habitats in Canada and beyond.
An ER CREC family protein regulates the egress proteolytic cascade in malaria parasites
Authors: Fierro Manuel A. , Asady Beejan , Brooks Carrie F. , Cobb David W. , Villegas Alejandra , Moreno Silvia N.J. , Muralidharan Vasant 
Published: October 2018

AbstractThe endoplasmic reticulum (ER) is thought to play an essential role during egress of malaria parasites because the ER is assumed to be the calcium (Ca2+) signaling hub and required for biogenesis of egress-related organelles. However, no proteins localized to the parasite ER have been shown to play a role in egress of malaria parasites. In this study, we generated conditional mutants of the Plasmodium falciparumEndoplasmic Reticulum-resident Calcium-binding protein (PfERC), a member of the CREC family. Knockdown of PfERC shows that this gene is essential for asexual growth of P. falciparum. Analysis of the intraerythrocytic lifecycle revealed that PfERC is essential for parasite egress but not required for protein trafficking or Ca2+ storage. We found that PfERC knockdown prevents the rupture of the parasitophorous vacuole membrane. This is because PfERC knockdown inhibited the proteolytic maturation of the subtilisin-like serine protease, SUB1. Using double mutant parasites, we show that PfERC is required for the proteolytic maturation of the essential aspartic protease, Plasmepsin X, which cleaves SUB1. Further, we show that processing of substrates downstream of the proteolytic cascade is inhibited by PfERC knockdown. Thus, these data establish the ER-resident CREC family protein, PfERC, as a key early regulator of the egress proteolytic cascade of malaria parasites.
Genetic Heterogeneity Profiling by Single Cell RNA Sequencing
Authors: Zhou Zilu , Xu Bihui , Minn Andy , Zhang Nancy R 
Published: October 2018

AbstractDetection of genetically distinct subclones and profiling the transcriptomic differences between them is important for studying the evolutionary dynamics of tumors, as well as for accurate prognosis and effective treatment of cancer in the clinic. For the profiling of intra-tumor transcriptional heterogeneity, single cell RNA-sequencing (scRNA-seq) is now ubiquitously adopted in ongoing and planned cancer studies. Detection of somatic DNA mutations and inference of clonal membership from scRNA-seq, however, is currently unreliable. We propose DENDRO, an analysis method for scRNA-seq data that detects genetically distinct subclones, assigns each single cell to a subclone, and reconstructs the phylogenetic tree describing the tumor’s evolutionary history. DENDRO utilizes information from single nucleotide mutations in transcribed regions and accounts for technical noise and expression stochasticity at the single cell level. The accuracy of DENDRO was benchmarked on spike-in datasets and on scRNA-seq data with known subpopulation structure. We applied DENDRO to delineate subclonal expansion in a mouse melanoma model in response to immunotherapy, highlighting the role of neoantigens in treatment response. We also applied DENDRO to primary and lymph-node metastasis samples in breast cancer, where the new approach allowed us to better understand the relationship between genetic and transcriptomic intratumor variation.
Two Chloroflexi classes independently evolved the ability to persist on atmospheric hydrogen and carbon monoxide
Authors: Islam Zahra F. , Cordero Paul R.F. , Feng Joanna , Chen Ya-Jou , Bay Sean K. , Jirapanjawat Thanavit , Gleadow Roslyn M. , Carere Carlo R. , Stott Matthew B. , Chiri Eleonora , Greening Chris 
Published: October 2018

AbstractBacteria within aerated environments often exist within a variety of dormant forms. In these states, bacteria endure adverse environmental conditions such as organic carbon starvation by decreasing metabolic expenditure and using alternative energy sources. In this study, we investigated the energy sources that facilitate the persistence of the environmentally widespread but understudied bacterial phylum Chloroflexi. A transcriptome study revealed thatThermomicrobium roseum(class Chloroflexia) extensively remodels its respiratory chain upon entry into stationary phase due to organic carbon limitation. Whereas primary dehydrogenases associated with heterotrophic respiration were downregulated, putative operons encoding enzymes involved in molecular hydrogen (H2), carbon monoxide (CO), and sulfur compound oxidation were significantly upregulated. Gas chromatography and microsensor experiments were used to show thatT. roseumaerobically respires H2and CO at a range of environmentally relevant concentrations to sub-atmospheric levels. Phylogenetic analysis suggests that the enzymes mediating atmospheric H2and CO oxidation, namely group 1h [NiFe]-hydrogenases and type I carbon monoxide dehydrogenases, are widely distributed in Chloroflexi genomes and have been acquired on at least two occasions through separate horizontal gene transfer events. Consistently, we confirmed that the sporulating isolateThermogemmatisporasp. T81 (class Ktedonobacteria) also oxidises atmospheric H2and CO during persistence. This study provides the first axenic culture evidence that atmospheric CO supports bacterial persistence and reports the third phylum to be experimentally shown to mediate the biogeochemically and ecologically important process of atmospheric H2oxidation. This adds to the growing body of evidence that atmospheric trace gases serve as dependable energy sources for the survival of dormant microorganisms.
Efficient assembly and long-term stability of defensive microbiomes via private resources and community bistability
Authors: Boza Gergely , Worsley Sarah F. , Yu Douglas W. , Scheuring Istvan 
Published: October 2018

AbstractUnderstanding the mechanisms promoting the assembly and maintenance of host-beneficial microbiomes is an open problem. An increasing amount of evidence supports the idea that animal and plant hosts can use ‘private resources’ and the ecological phenomenon known as ‘community bistability’ to favour some microbial strains over others. We briefly review empirical evidence showing that hosts can: (i) protect the growth of beneficial strains in an isolated habitat, (ii) use antibiotic compounds to suppress non-beneficial, competitor strains, and (iii) provide resources (for a limited time) that only beneficial strains are able to translate into an increased rate of growth, reproduction, or antibiotic production. We then demonstrate in a spatially explicit, individual-based model that these three mechanisms act similarly by selectively promoting the initial proliferation of preferred strains, that is, by acting as a private resource. By explicitly modelling localized microbial interactions and diffusion dynamics, we further show that an intermediate level of antibiotic diffusion is the most efficient mechanism in promoting preferred strains and that that there is a wide range of conditions under which hosts can promote the assembly of a self-sustaining defensive microbiome. This, in turn, supports the idea that hosts readily evolve to promote host-beneficial defensive microbiomes.
Oxygen plasma focused ion beam scanning electron microscopy for biological samples
Authors: Sergey Gorelick , Denis Korneev , Ava Handley , Gediminas Gervinskas , Viola Oorschot , Owen L. Kaluza , Ruby H.P. Law , Moira O’ Bryan , Roger Pocock , James C. Whisstock , Alex de Marco 
Published: October 2018

AbstractOver the past decade, gallium Focused Ion Beam-Scanning Electron Microscopy (FIB-SEM) has been established as a key technology for cellular tomography. The utility of this approach, however, is severely limited both by throughput and the limited selection of compatible sample preparation protocols. Here, we address these limitations and present oxygen plasma FIB (O-PFIB) as a new and versatile tool for cellular FIB-SEM tomography. Oxygen displays superior resin compatibility to other ion beams and produces curtain-free surfaces with minimal polishing. Our novel approach permits more flexible sample preparation and 30% faster data collection when compared to using gallium ion sources. We demonstrate this alternative FIB is applicable to a variety of embedding procedures and biological samples including brain tissue and whole organisms. Finally, we demonstrate the use of O-PFIB to produce targeted FIB-SEM tomograms through fiducial free en-block correlative light and electron microscopy.
Resistance Gene-Directed Genome Mining of 50 Aspergillus species
Authors: Kjærbølling Inge , Vesth Tammi , Andersen Mikael R. 
Published: October 2018

AbstractFungal secondary metabolites are a rich source of valuable natural products. Genome sequencing have revealed an enormous potential from predicted biosynthetic gene clusters. It is however currently a time consuming task and an unfeasible task to characterize all biosynthetic gene cluster and to identify possible uses of the compounds. A rational approach is needed to identify promising gene clusters responsible for producing valuable compounds. Several valuable bioactive clusters have been shown to include a resistance gene which is a paralog of the target gene inhibited by the compound. This mechanism can be used to design a rational approach selecting those clusters.We have developed a pipeline FRIGG (Fungal Resistance Gene-directed Genome mining) identifying putative resistance genes found in biosynthetic gene clusters based on homology patterns of the cluster genes. The FRIGG pipeline has been run using 51 Aspergillus and Penicillium genomes, identifying 72 unique protein families with putative resistance genes using various settings in the pipeline. The pipeline was also able to identify the characterized resistance gene inpE from the Fellutamide B cluster thereby validating the approach.We have successfully developed an approach identifying putative valuable bio-active clusters based on a specific resistance mechanism. This approach will be highly useful as an ever increasing amount of genomic data becomes available — the art of identifying and selecting clusters producing novel valuable compounds will only become more crucial.ImportanceSpecies belonging to the Aspergillus genus are known to produce a large number of secondary metabolites, some of these compounds are bioactive and used as pharmaceuticals such as penicillin, cyclosporin and statin. With whole genome sequencing it became apparent that the genetic potential for secondary metabolite production is much bigger than expected. As an increasing number of species are whole genome sequenced an immense number of secondary metabolite genes are predicted and the question of how to selectively identify novel bioactive compounds from this information arises. To address this question, we have created a pipeline identifying genes likely involved in the production of bioactive compounds based on a resistance gene hypothesis approach.