bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Properties of Silicone Gel Breast Implants
Authors: Jewell Mark L , Bengtson Bradley P , Smither Kate , Nuti Gina , Perry TracyAnn 
Published: April 2018

Abstract

Background
Surgical applications using breast implants are individualized operations to fill and shape the breast. Physical properties beyond shape, size, and surface texture are important considerations during implant selection.

Objectives
Compare form stability, gel material properties, and shell thickness of textured shaped, textured round, and smooth round breast implants from 4 manufacturers: Allergan, Mentor, Sientra, and Establishment Labs, through bench testing.

Methods
Using a mandrel height gauge, form stability was measured by retention of dimensions on device movement from a horizontal to vertical supported orientation. Dynamic response of the gel material (gel cohesivity, resistance to gel deformation, energy absorption) was measured using a synchronized target laser following application of graded negative pressure. Shell thickness was measured using digital thickness gauge calipers.

Results
Form stability, gel material properties, and shell thickness differed across breast implants. Of textured shaped devices, Allergan Natrelle 410 exhibited greater form stability than Mentor MemoryShape and Sientra Shaped implants. Allergan Inspira round implants containing TruForm 3 gel had greater form stability, higher gel cohesivity, greater resistance to gel deformation, and lower energy absorption than those containing TruForm 2 gel and in turn, implants containing TruForm 1 gel. Shell thickness was greater for textured vs smooth devices, and differed across styles.

Conclusions
Gel cohesivity, resistance to gel deformation, and energy absorption are directly related to form stability, which in turn determines shape retention. These characteristics provide information to aid surgeons choosing an implant based on surgical application, patient tissue characteristics, and desired outcome.
Base-pair resolution detection of transcription factor binding site by deep deconvolutional network
Authors: Salekin Sirajul , Zhang Jianqiu Michelle , Huang Yufei 
Published: May 2018

Abstract

Motivation
Transcription factor (TF) binds to the promoter region of a gene to control gene expression. Identifying precise TF binding sites (TFBSs) is essential for understanding the detailed mechanisms of TF-mediated gene regulation. However, there is a shortage of computational approach that can deliver single base pair resolution prediction of TFBS.

Results
In this paper, we propose DeepSNR, a Deep Learning algorithm for predicting TF binding location at Single Nucleotide Resolution de novo from DNA sequence. DeepSNR adopts a novel deconvolutional network (deconvNet) model and is inspired by the similarity to image segmentation by deconvNet. The proposed deconvNet architecture is constructed on top of ‘DeepBind’ and we trained the entire model using TF-specific data from ChIP-exonuclease (ChIP-exo) experiments. DeepSNR has been shown to outperform motif search–based methods for several evaluation metrics. We have also demonstrated the usefulness of DeepSNR in the regulatory analysis of TFBS as well as in improving the TFBS prediction specificity using ChIP-seq data.

Availability and implementation
DeepSNR is available open source in the GitHub repository (https://github.com/sirajulsalekin/DeepSNR)

Supplementary information
Supplementary data are available at Bioinformatics online.
Two C++ libraries for counting trees on a phylogenetic terrace
Authors: Biczok R , Bozsoky P , Eisenmann P , Ernst J , Ribizel T , Scholz F , Trefzer A , Weber F , Hamann M , Stamatakis A 
Published: May 2018

Abstract

Motivation
The presence of terraces in phylogenetic tree space, i.e. a potentially large number of distinct tree topologies that have exactly the same analytical likelihood score, was first described by Sanderson et al. However, popular software tools for maximum likelihood and Bayesian phylogenetic inference do not yet routinely report, if inferred phylogenies reside on a terrace, or not. We believe, this is due to the lack of an efficient library to (i) determine if a tree resides on a terrace, (ii) calculate how many trees reside on a terrace and (iii) enumerate all trees on a terrace.

Results
In our bioinformatics practical that is set up as a programming contest we developed two efficient and independent C++ implementations of the SUPERB algorithm by Constantinescu and Sankoff (1995) for counting and enumerating trees on a terrace. Both implementations yield exactly the same results, are more than one order of magnitude faster, and require one order of magnitude less memory than a previous thirrd party python implementation.

Availability and implementation
The source codes are available under GNU GPL at https://github.com/terraphast.

Supplementary information
Supplementary data are available at Bioinformatics online.
Repeat Syphilis Is More Likely to Be Asymptomatic in HIV-Infected Individuals: A Retrospective Cohort Analysis With Important Implications for Screening
Authors: Kenyon Chris , Osbak Kara Krista , Apers Ludwig 
Published: April 2018

AbstractThere is conflicting evidence as to whether repeat syphilis is more likely to present asymptomatically than initial syphilis. If it is, then this would motivate more frequent and long-term syphilis screening in persons with a history of multiple episodes of syphilis. We conducted detailed folder reviews of all individuals with 4 or more diagnoses of syphilis between 2000 and 2017 at the Institute of Tropical Medicine, Antwerp, and assessed if there was a difference in the proportion presenting with symptomatic (primary and secondary) vs asymptomatic (latent) syphilis in initial vs repeat syphilis. Forty-five clients with 4 or more episodes of syphilis were included in the study. All were HIV-infected. Repeat episodes of syphilis were less likely to be symptomatic than initial episodes (35/160 [21.9%] vs 28/45 [62.2%]; P &lt; .001). Frequent screening in those with HIV infection may be the only way to diagnose repeat episodes of syphilis. Care providers can use this information to motivate persons with multiple episodes of syphilis to be screened every 3 to 6 months.
Visceral Fat Is Associated With Mucosal Healing of Infliximab Treatment in Crohn’s Disease
Authors: Shen Weisong , Cao Lei , Li Yi , Cai Xingchen , Ge Yuanyuan , Zhu Weiming 
Published: May 2018

BACKGROUND:
Visceral fat is the pathogenesis of Crohn’s disease and is associated with disease status.

OBJECTIVE:
This study aimed to evaluate the effect of the visceral fat on mucosal healing in patients with Crohn’s disease after infliximab induction therapy

DESIGN:
This was a retrospective study.

SETTINGS:
The study was conducted in a tertiary referral hospital.

PATIENTS:
Between 2011 and 2017, 97 patients with Crohn’s disease with the presence of ulcers underwent infliximab therapy.

MAIN OUTCOME MEASURES:
We studied them retrospectively. Mucosal healing was the end point. Patients composed 2 groups: mucosal healing and no mucosal healing. Univariate, multivariate, and receiver operating characteristic curve analyses determined the predictive value of the visceral fat area.

RESULTS:
Univariate analysis showed a statistically significant difference in the smoking history between the groups. Mucosal healing rates after infliximab were lower among active smokers (p = 0.022). Healed patients had significantly less visceral fat area before therapy (47.76 ± 4.94 vs 75.88 ± 5.55; p = 0.000) and a lower mesenteric fat index (0.52 ± 0.04 vs 0.89 ± 0.07; p = 0.000). There was no significant difference in the subcutaneous fat area (87.39 ± 5.01 vs 93.31 ± 6.95; p = 0.500). Multivariate analysis showed that only visceral fat area (OR = 0.978 (95% CI, 0.964–0.992); p = 0.002) and smoking history (OR = 0.305 (95% CI, 0.089–0.996); p = 0.041) were independent factors for mucosal healing. Receiver operating characteristic curve analysis showed predictive cutoff values of 61.5 cm2 and 0.62 for visceral fat area and mesenteric fat index.

LIMITATIONS:
This was a retrospective study.

CONCLUSIONS:
There was an association between increased visceral fat area and attenuated mucosal healing after infliximab therapy in biologically naive patients with Crohn’s disease, indicating a need for earlier increased infliximab doses among patients with increased visceral fat. See Video Abstract at http://links.lww.com/DCR/A590.
Using Endoscopic Submucosal Dissection as a Routine Component of the Standard Treatment Strategy for Large and Complex Colorectal Lesions in a Western Tertiary Referral Unit
Authors: Emmanuel Andrew , Gulati Shraddha , Burt Margaret , Hayee Bu’Hussain , Haji Amyn 
Published: May 2018

BACKGROUND:
Colorectal endoscopic submucosal dissection results in high rates of en bloc resection, few recurrences, and accurate diagnosis, and it is useful in lesions with significant fibrosis. However, endoscopic submucosal dissection has not been widely adopted by Western endoscopists and the published experience from Western centers is very limited.

OBJECTIVES:
This study aims to report the outcomes from a UK tertiary center using colorectal endoscopic submucosal dissection as part of a standard lesion specific treatment approach.

DESIGN:
This was a retrospective study.

SETTING:
The study was conducted in a tertiary referral unit for interventional endoscopy in the United Kingdom.

PATIENTS:
A total of 116 colorectal lesions were resected using endoscopic submucosal dissection or hybrid endoscopic submucosal dissection in 107 patients.

MAIN OUTCOME MEASURES:
Outcomes included complications, recurrence, requirement for surgery, en bloc and R0 resection.

RESULTS:
One hundred sixteen lesions (mean size 58.8mm) were resected using endoscopic submucosal dissection (n = 58) and hybrid endoscopic submucosal dissection (n = 58). Eighty-two (70.7%) had failed attempts at resection (n = 58) or extensive sampling before referral. Twelve contained invasive adenocarcinoma; endoscopic resection was curative in 6. Only 2 of 6 patients with noncurative endoscopic resection agreed to surgery, and none had lymph node metastases. Six of 7 perforations were successfully treated with endoscopic clips. Where endoscopic submucosal dissection was used alone, en bloc resection was achieved in 93% and R0 resection was achieved in 91%. Two patients experienced recurrence; both were managed with endoscopic resection.

LIMITATIONS:
This was a retrospective study. Procedures were planned as endoscopic submucosal dissection, but some may have been converted to hybrid endoscopic submucosal dissection and not recorded.

CONCLUSION:
Colorectal endoscopic submucosal dissection can be used in a Western center as part of a standard lesion-specific approach to deliver effective organ-conserving treatment to patients with large challenging lesions. Lesion assessment in Western practice should be improved to reduce the incidence of prior heavy manipulation and to guide appropriate referral. See Video Abstract at http://links.lww.com/DCR/A601.
Combination attenuation offers strategy for live-attenuated coronavirus vaccines
Authors: Menachery Vineet D. , Gralinski Lisa E. , Mitchell Hugh D. , Dinnon Kenneth H. , Leist Sarah R. , Yount Boyd L. , McAnarney Eileen T. , Graham Rachel L. , Waters Katrina M. , Baric Ralph S. 
Published: April 2018

AbstractWith an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live-attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2’O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the SARS-CoV mouse model, a NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2’O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2’O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live-attenuated coronavirus vaccines.SignificanceEmergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations like the aged and immune-compromised. This study illustrates that despite success in young models, the NSP16 mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the NSP16 mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for NSP16 attenuation as a major component of future live-attenuated coronavirus vaccines.
Octapeptin C4 Induces Less Resistance and Novel Mutations in an Epidemic Carbapenemase-producingKlebsiella pneumoniaeST258 Clinical Isolate Compared to Polymyxins
Authors: Pitt Miranda E. , Cao Minh Duc , Butler Mark S. , Ramu Soumya , Ganesamoorthy Devika , Blaskovich Mark A. T. , Coin Lachlan J. M. , Cooper Matthew A. 
Published: April 2018

ABSTRACTPolymyxin B and E (colistin) have been pivotal in the treatment of extensively drug-resistant (XDR) Gram-negative bacterial infections, with increasing use over the past decade. Unfortunately, resistance to these antibiotics is rapidly emerging. The structurally-related octapeptin C4 (OctC4) has shown significant potency against XDR bacteria, including against polymyxin-resistant (Pmx-R) strains, but its mode of action remains undefined. We sought to compare and contrast the acquisition of XDRKlebsiella pneumoniae(ST258) resistancein vitrowith all three lipopeptides to help elucidate the mode of action of the drugs and potential mechanisms of resistance evolution. Strikingly, 20 days of exposure to the polymyxins resulted in a dramatic (1000-fold) increase in the minimum inhibitory concentration (MIC) for the polymyxins, reflecting the evolution of resistance seen in clinical isolates, whereas for OctC4 only a 4-fold increase was witnessed. There was no cross-resistance observed between the polymyxin - and octapeptin-induced resistant strains. Sequencing revealed previously known gene alterations for polymyxin resistance, includingcrrB,mgrB,pmrB,phoPQandyciM, and novel mutations inqseC. In contrast, mutations inmlaDFandpqiB, 1genes related to phospholipid transport, were found in octapeptin-resistant isolates. Mutation effects were validated via complementation assays. These genetic variations were reflected in phenotypic changes to lipid A. Pmx-R isolates increased 4-amino-4-deoxy-arabinose fortification to phosphate groups of lipid A, whereas OctC4 induced strains harbored a higher abundance of hydroxymyristate and palmitoylate. The results reveal a differing mode of action compared to polymyxins which provides hope for future therapeutics to combat the increasingly threat of XDR bacteria.
Corals sustain growth but not skeletal density across the Florida Keys Reef Tract despite ongoing warming
Authors: Rippe John , Baumann Justin H. , De Leener Daphne N. , Aichelman Hannah E. , Friedlander Eric B. , Davies Sarah W. , Castillo Karl D. 
Published: April 2018

ABSTRACTThrough the continuous growth of their carbonate skeletons, corals record invaluable information about past environmental conditions and their effect on colony fitness. Here, we characterize century-scale growth records of inner and outer reef corals across ~200 km of the Florida Keys Reef Tract (FKRT) using skeletal cores extracted from two ubiquitous reef-building species, Siderastrea siderea and Pseudodiploria strigosa. We find that corals across the FKRT have sustained extension and calcification rates over the past century but have experienced a long-term reduction in skeletal density, regardless of reef zone. Notably, P. strigosa colonies exhibit temporary reef zone-dependent reductions in extension rate corresponding to two known extreme temperature events in 1969-70 and 1997-98. We propose that the subtropical climate of the FKRT may buffer corals from chronic growth declines associated with climate warming, though the significant reduction in skeletal density may indicate underlying vulnerability to present and future trends in ocean acidification.
DsbA is a redox-switchable mechanical chaperone
Authors: Eckels Edward C. , Chaudhuri Deep , Chakraborty Soham , Echelman Daniel J. , Haldar Shubhasis 
Published: April 2018

AbstractDsbA is a ubiquitous bacterial oxidoreductase that associates with substrates during and after translocation, yet its involvement in protein folding and translocation remains an open question. Here we demonstrate a redox-controlled chaperone activity of DsbA, on both cysteine-containing and cysteine-free substrate, using a magnetic tweezers-based single molecule force spectroscopy that enables independent measurements of oxidoreductase activity and chaperone behavior. Interestingly we found, this chaperone activity is tuned by the oxidation state of DsbA; oxidized DsbA is a strong promoter of folding, but the effect is weakened by reduction of the catalytic CXXC motif. We further localize the chaperone binding site of DsbA using a seven-residue peptide which effectively blocks the chaperone activity. We calculated that DsbA assisted folding of proteins in the periplasm generates enough mechanical work to decrease the ATP consumption needed for periplasmic translocation by up to 33%. In turn, pharmacologic inhibition of this chaperone activity may open up a new class of anti-virulence agents.
Helicase Promotes Replication Re-initiation from an RNA Transcript
Authors: Sun Bo , Singh Anupam , Sultana Shemaila , Inman James T. , Patel Smita S. , Wang Michelle D. 
Published: April 2018

AbstractTo ensure accurate DNA replication, a replisome must effectively overcome numerous obstacles on its DNA substrate. After encountering an obstacle, a progressing replisome often aborts DNA synthesis but continues to unwind the DNA, resulting in a gap in the newly replicated DNA. However, little is known about how DNA synthesis is resumed downstream of an obstacle. Here, we examine the consequences of a non-replicating replisome collision with a co-directional RNA polymerase (RNAP). Using single-molecule and ensemble methods, we find that T7 helicase interacts strongly with a non-replicating T7 DNA polymerase (DNAP) at a replication fork. As the helicase advances the fork, the DNAP also moves forward processively, via its association with the helicase. The presence of the DNAP, in turn, increases both helicase’s processivity and unwinding rate. We show that such a DNAP, together with its helicase, is indeed able to actively disrupt a stalled transcription elongation complex, and then initiates replication using the RNA transcript as a primer. These observations exhibit T7 helicase’s novel role in replication re-initiation, independent of replication restart proteins or primase.
Creating Standards for Evaluating Tumour Subclonal Reconstruction
Authors: Salcedo Adriana , Tarabichi Maxime , Espiritu Shadrielle Melijah G. , Deshwar Amit G. , David Matei , Wilson Nathan M. , Dentro Stefan , Wintersinger Jeff A. , Liu Lydia Y. , Ko Minjeong , Sivanandan Srinivasan , Zhang Hongjiu , Zhu Kaiyi , Yang Tai-Hsien Ou , Chilton John M. , Buchanan Alex , Lalansingh Christopher M. , P’ng Christine , Anghel Catalina V. , Umar Imaad , Lo Bryan , Zou William ,   DREAM SMC-Het Participants, Simpson Jared T. , Stuart Joshua M. , Anastassiou Dimitris , Guan Yuanfang , Ewing Adam D. , Ellrott Kyle , Wedge David C. , Morris Quaid D. , Van Loo Peter , Boutros Paul C. 
Published: April 2018

AbstractTumours evolve through time and space. Computational techniques have been developed to infer their evolutionary dynamics from DNA sequencing data. A growing number of studies have used these approaches to link molecular cancer evolution to clinical progression and response to therapy. There has not yet been a systematic evaluation of methods for reconstructing tumour subclonality, in part due to the underlying mathematical and biological complexity and to difficulties in creating gold-standards. To fill this gap, we systematically elucidated the key algorithmic problems in subclonal reconstruction and developed mathematically valid quantitative metrics for evaluating them. We then created approaches to simulate realistic tumour genomes, harbouring all known mutation types and processes both clonally and subclonally. We then simulated 580 tumour genomes for reconstruction, varying tumour read-depth and benchmarking somatic variant detection and subclonal reconstruction strategies. The inference of tumour phylogenies is rapidly becoming standard practice in cancer genome analysis; this study creates a baseline for its evaluation.
The hydrolase LpqI primes mycobacterial peptidoglycan recycling
Authors: Moynihan Patrick J. , Cadby Ian T. , Veerapen Natacha , Jankute Monika , Crosatti Marialuisa , Mukamolova Galina V. , Lovering Andrew L. , Besra Gurdyal S. 
Published: May 2018

AbstractGrowth and division by most bacteria requires remodeling and cleavage of their cell wall. A byproduct of this process is the generation of free peptidoglycan (PG) fragments known as muropeptides. These muropeptides are recycled in many model organisms, where the bacteria can harness their unique nature as a signal for cell wall damage. These molecules also serve as important signals for hosts where binding to specific receptors reports on the presence of intracellular bacteria. Despite this critical role for muropeptides, it has long been thought that pathogenic mycobacteria such asMycobacterium tuberculosisdo not recycle their PG. Herein we show for the first time thatM. tuberculosisandMycobacterium bovisBCG are able to recycle components of their PG. We demonstrate that the core-mycobacterial genelpqI, encodes an authentic NagZ β-N-acetylglucosaminidase and that it is essential for PG-derived amino sugar recyclingviaan unusual pathway. By characterizing anM. bovisBCG strain lackinglpqIwe are also able to show that stem-peptide recycling proceeds independent of amino sugar recovery and loss oflpqIleads to antimicrobial resistancein vitro. Together these data provide a critical first step in understanding how mycobacteria recycle their peptidoglycan.