bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Effectiveness of Retromuscular and Intraperitoneal Repair: What Is the Value of Posterior Sheath Reconstruction?
Authors: Carney Martin J. , Messa Charles A. , Weissler Jason M. , Shakir Sameer , Wes Ari M. , Enriquez Fabiola A. , Hsu Jesse Y. , Roth J. Scott , Kovach Stephen J. , Fischer John P. 
Published: April 2018

Background:
The authors hypothesize that posterior sheath reconstruction to achieve retromuscular mesh placement provides outcomes comparable to traditional retromuscular mesh placement and superior to intraperitoneal repair.

Methods:
Patients were divided into three groups: (1) retromuscular mesh placement with repaired posterior sheath defects, (2) retromuscular repair with an intact posterior sheath, and (3) intraperitoneal repair. Primary outcomes included recurrence, surgical-site occurrences, and cost.

Results:
Overall, 179 patients were included. Posterior sheath defects were repaired primarily with absorbable suture or biological mesh. Recurrence rates differed significantly between standard retromuscular repair and intraperitoneal repair groups (p < 0.009), trended toward significance between repaired posterior sheath and intraperitoneal repair groups (p < 0.058), and showed no difference between repaired posterior sheath and standard retromuscular repair (p < 0.608). Retromuscular repair was clinically protective and cost-effective.

Conclusions:
This analysis of posterior sheath reconstruction suggests outcomes comparable to traditional retromuscular repair and a trend toward superiority compared with intraperitoneal repair. Achieving retromuscular closure appears to demonstrate clinical and cost efficacy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Carpal Tunnel Syndrome Management in Breast Cancer Survivors at Risk for Lymphedema: A Markov Model
Authors: Retrouvey Helene , Krahn Murray , Baltzer Heather L. 
Published: April 2018

Background:
Breast cancer survivors that have undergone axillary lymph node dissection have an increased risk of developing same-side upper extremity lymphedema. Patients with carpal tunnel syndrome in the ipsilateral limb may not receive appropriate surgical therapy (carpal tunnel release) because of concerns that it may trigger or worsen lymphedema.

Methods:
A state transition cohort model was used to evaluate the treatment options for breast cancer survivors at risk of upper extremity lymphedema presenting with carpal tunnel syndrome. The model reflected three treatment strategies: (1) early surgical intervention, (2) delayed surgical intervention, or (3) nonsurgical management. Both life-years and quality-adjusted life-years were modeled over a 30-year time horizon.

Results:
Over a 30-year time horizon, the preferred strategy was delayed surgery, which resulted in 21.41 quality-adjusted life-years. Early surgery and nonsurgical management yielded 20.42 and 21.06 quality-adjusted life-years, respectively. The model was robust and was not sensitive to variation in any of the parameters within the clinically plausible ranges.

Conclusions:
Based on this decision analytic model, the optimal choice for breast cancer survivors with mild carpal tunnel syndrome who are at risk for lymphedema would be delaying surgery until severe symptoms develop. This strategy balances the potential increased risk of lymphedema following carpal tunnel release with the decreased long-term risk of severe carpal tunnel syndrome. The model comprehensively assesses a controversial area in the breast cancer and hand surgery literature to inform decision-making for patients and clinicians.
Self-awareness of Driving Ability in the Healthy Elderly and Patients With Mild Cognitive Impairment (MCI)
Authors: Fragkiadaki Stella , Beratis Ion N. , Kontaxopoulou Dionysia , Pavlou Dimosthenis , Andronas Nikolaos , Papanicolaou Andrew , Economou Alexandra , Yannis George , Papageorgiou Sokratis G. 
Published: April 2018

Introduction:
According to latest research, a percentage of cognitively impaired drivers fail to recognize their areas of weakness and overestimate their driving abilities.

Methods:
Twenty-seven individuals with amnestic mild cognitive impairment (MCI) and 26 healthy elderly drivers participated in a driving simulator study. After the driving assessment, participants were asked to self-evaluate their performance in comparison with what they considered as average for people of similar age and educational level.

Results:
According to the applied mixed analysis of variance model, the MCI patients presented increased difficulties in estimating their driving performance to a greater extent in the rural environment in comparison with the urban condition.

Discussion:
Our findings suggest that the ability of MCI patients to evaluate their driving performance accurately seems to be enhanced or compromised, depending on the number of cues available in their environment, suggesting that providing feedback may improve their metacognitive abilities.
Improved Analysis of Phage ImmunoPrecipitation Sequencing (PhIP-Seq) Data Using a Z-score Algorithm
Authors: Yuan Tiezheng , Mohan Divya , Laserson Uri , Ruczinski Ingo , Baer Alan N. , Larman H. Benjamin 
Published: April 2018

AbstractPhage ImmunoPrecipitation Sequencing (PhIP-Seq) is a massively multiplexed, phage-display based methodology for analyzing antibody binding specificities, with several advantages over existing techniques, including the uniformity and completeness of proteomic libraries, as well as high sample throughput and low cost. Data generated by the PhIP-Seq assay are unique in many ways. The only published analytical approach for these data suffers from important limitations. Here, we propose a new statistical framework with several improvements. Using a set of replicate mock immunoprecipitations (negative controls lacking antibody input) to generate background binding distributions, we establish a statistical model to quantify antibody-dependent changes in phage clone abundance. Our approach incorporates robust regression of experimental samples against the mock IPs as a means to calculate the expected phage clone abundance, and provides a generalized model for calculating each clone’s expected abundance-associated standard deviation. In terms of bias removal and detection sensitivity, we demonstrate that this z-score algorithm outperforms the previous approach. Further, in a large cohort of autoantibody-defined Sjögren’s Syndrome (SS) patient sera, PhIP-Seq robustly identified Ro52, Ro60, and SSB/La as known autoantigens associated with SS. In an effort to identify novel SS-specific binding specificities, SS z-scores were compared with z-scores obtained by screening Ropositive sera from patients with systemic lupus erythematosus (SLE). This analysis did not yield any commonly targeted SS-specific autoantigens, suggesting that if they exist at all, their epitopes are likely to be discontinuous or post-translationally modified. In summary, we have developed an improved algorithm for PhIP-Seq data analysis, which was validated using a large set of sera with clinically characterized autoantibodies. This z-score approach will substantially improve the ability of PhIP-Seq to detect and interpret antibody binding specificities. The associated Python code is freely available for download here: https://github.com/LarmanLab/PhIP-Seq-Analyzer.
Three new genome assemblies support a rapid radiation in Musa acuminata (wild banana)
Authors: Rouard M , Droc G , Martin G , Sardos J , Hueber Y , Guignon V , Cenci A , Geigle B , Hibbins M S , Yahiaoui N , Baurens F-C , Berry V , Hahn M W , D’Hont A , Roux N 
Published: April 2018

AbstractEdible bananas result from interspecific hybridization between Musa acuminata and Musa balbisiana, as well as among subspecies in M. acuminata. Four particular M. acuminata subspecies have been proposed as the main contributors of edible bananas, all of which radiated in a short period of time in southeastern Asia. Clarifying the evolution of these lineages at a whole-genome scale is therefore an important step toward understanding the domestication and diversification of this crop. This study reports the de novo genome assembly and gene annotation of a representative genotype from three different subspecies of M. acuminata. These data are combined with the previously published genome of the fourth subspecies to investigate phylogenetic relationships and genome evolution. Analyses of shared and unique gene families reveal that the four subspecies are quite homogenous, with a core genome representing at least 50% of all genes and very few M. acuminata species-specific gene families. Multiple alignments indicate high sequence identity between homologous single copy-genes, supporting the close relationships of these lineages. Interestingly, phylogenomic analyses demonstrate high levels of gene tree discordance, due to both incomplete lineage sorting and introgression. This pattern suggests rapid radiation within Musa acuminata subspecies that occurred after the divergence with M. balbisiana. Introgression between M. a. ssp. malaccensis and M. a. ssp. burmannica was detected across a substantial portion of the genome, though multiple approaches to resolve the subspecies tree converged on the same topology. To support future evolutionary and functional analyses, we introduce the PanMusa database, which enables researchers to exploration of individual gene families and trees.
Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism
Authors: Fumagalli Matteo , Camus Stephane M. , Diekmann Yoan , Burke Alice , Camus Marine D. , Norman Paul J. , Joseph Agnel Praveen , Abi-Rached Laurent , Benazzo Andrea , Rasteiro Rita , Mathieson Iain , Topf Maya , Parham Peter , Thomas Mark G. , Brodsky Frances M. 
Published: April 2018

ABSTRACTCHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encodingCLTCL1gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogousCLTCgene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retainingCLTCL1, strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequencyCLTCL1allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, attenuating its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22’s role in metabolism and have potential to differentially influence the human insulin response.
Alopecia areata susceptibility variant identified by MHC risk haplotype sequencing reproduces symptomatic patched hair loss in mice
Authors: Oka Akira , Takagi Atsushi , Komiyama Etsuko , Mano Shuhei , Hosomichi Kazuyoshi , Suzuki Shingo , Motosugi Nami , Hatanaka Tomomi , Kimura Minoru , Takahashi Ueda Mahoko , Nakagawa So , Miura Hiromi , Ohtsuka Masato , Haida Yuko , Tanaka Masayuki , Komiyama Tomoyoshi , Otomo Asako , Hadano Shinji , Mabuchi Tomotaka , Beck Stephan , Inoko Hidetoshi , Ikeda Shigaku 
Published: April 2018

AbstractBackgroundAlopecia areata (AA) is a highly heritable multifactorial and complex disease. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a region in the human genome known to be associated with AA as compared to other regions.ResultsBy sequencing MHC risk haplotypes, we identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Using CRISPR/Cas9 for allele-specific genome editing, we then phenocopied AA symptomatic patched hair loss in mice engineered to carry theCchcr1risk allele. Skin biopsies of these alopecic mice showed strong up-regulation of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Using transcriptomics findings, we further identified CCHCR1 as a novel component of hair shafts and cuticles in areas where the engineered alopecic mice displayed fragile and impaired hair.ConclusionsThese results suggest an alternative mechanism for the aetiology of AA based on aberrant keratinization, in addition to generally well-known autoimmune events.
Strength in numbers: collaborative science for new experimental model systems
Authors: Waller Ross F. , Cleves Phillip A. , Rubio-Brotons Maria , Woods April , Bender Sara J. , Edgcomb Virginia , Gann Eric R. , Jones Adam C. , Teytelman Leonid , von Dassow Peter , Wilhelm Steven W. , Collier Jackie L. 
Published: April 2018

AbstractOur current understanding of biology is heavily based on the contributions from a small number of genetically tractable model organisms. Most eukaryotic phyla lack such experimental models, and this limits our ability to explore the molecular mechanisms that ultimately define their biology, ecology, and diversity. In particular, marine protists suffer from a paucity of model organisms despite playing critical roles in global nutrient cycles, food webs, and climate. To address this deficit, an initiative was launched in 2015 to foster development of ecologically and taxonomically diverse marine protist genetic models. This multifaceted, complex but important challenge required a highly collaborative community-based approach. Herein we describe this approach, the advances achieved, and the lessons learned by participants in this novel community-based model for research.
Probing the chemical-biological relationship space with the Drug Target Explorer
Authors: Allaway Robert , Rosa Salvatore La , Guinney Justin , Gosline Sara 
Published: April 2018

AbstractModern phenotypic high-throughput screens (HTS) present several challenges including identifying the target(s) that mediate the effect seen in the screen, characterizing ‘hits’ with a polypharmacologic target profile, and contextualizing screen data within the large potential space of drugs and biological screening model combinations. To address these challenges, we developed an interactive web application that enables exploration of the chemical-biological interaction space. Compound-target interaction data from public resources were quantified for over 280,000 molecules. Each molecule was annotated with a name and chemical structure, and every target was annotated with gene identifiers. The Drug-Target Explorer allows users to query molecules within this database of experimentally-derived and curated compound-target interactions and identify structurally similar molecules. It also enables network-based visualizations of the compound-target interaction space, and incorporates comparisons to publicly-availablein vitroHTS datasets. Users can also identify compounds given one or more targets of interest. The Drug Target Explorer is a multifunctional platform for exploring chemical space as it relates to biological targets, and may be useful at several steps along the drug development pipeline including target discovery, structure-activity relationship, and lead compound identification studies.
Force-based three-dimensional model predicts mechanical drivers of cell sorting
Authors: Revell Christopher , Blumenfeld Raphael , Chalut Kevin 
Published: April 2018

AbstractMany biological processes, including tissue morphogenesis, are driven by mechanical sorting. However, the primary mechanical drivers of cell sorting remain controversial, in part because there remains a lack of appropriate threedimensional computational methods to probe the mechanical interactions that drive sorting. To address this important issue, we developed a three-dimensional, local force-based simulation method to enable such investigation into the sorting mechanisms of multicellular aggregates. Our method utilises the subcellular element method, in which cells are modeled as collections of locally-interacting force-bearing elements, accommodating cell growth and cell division. We define two different types of intracellular elements, assigning different attributes to boundary elements to model a cell cortex, which mediates the interfacial interaction between different cells. By tuning interfacial adhesion and tension in each cell cortex, we can control and predict the degree of sorting in cellular aggregates. The method is validated by comparing the interface areas of simulated cell doublets to experimental data and to previous theoretical work. We then define numerical measures of sorting and investigate the effects of mechanical parameters on the extent of sorting in multicellular aggregates. Using this method, we find that a minimum adhesion is required for differential interfacial tension to produce inside-out sorting of two cell types with different mechanical phenotypes. We predict the value of the minimum adhesion, which is in excellent agreement with observations in several developmental systems. We also predict the level of tension asymmetry needed for robust sorting. The generality and flexibility of the method make it applicable to tissue self-organization in a myriad of biological processes, such as tumorigenesis and embryogenesis.
Influence of different modes of morphological character correlation on phylogenetic tree inference
Authors: Guillerme Thomas , Brazeau Martin D. 
Published: April 2018

AbstractPhylogenetic analysis algorithms require the assumption of character independence - a condition generally acknowledged to be violated by morphological data. Correlation between characters can originate from intra-organismal features, shared phylogenetic history or forced by particular character-state coding schemes. Although the two first sources can be investigated by biologists a posteriori and the third one can be avoided a priori with good practices, phylogenetic software do not distinguish between any of them.In this study, we propose a new metric of raw character difference as a proxy for character correlation. Using thorough simulations, we test the effect of increasing or decreasing character differences on tree topology. Overall, we found an expected positive effect of reducing character correlations on recovering the correct topology. However, this effect is less important for matrices with a small number of taxa (25 in our simulations) where reducing character correlation is not more effective than randomly drawing characters. Furthermore, in bigger matrices (350 characters), there is a strong effect of the inference method with Bayesian trees being consistently less affected by character correlation than maximum parsimony trees.These results suggest that ignoring the problem of character correlation or independence can often impact topology in phylogenetic analysis. However, encouragingly, they also suggest that, unless correlation is actively maximised or minimised, probabilistic methods can easily accommodate for a random correlation between characters.
Edge orientation perception during active touch
Authors: Olczak Derek , Sukumar Vaishnavi , Andrew Pruszynski J. 
Published: April 2018

AbstractPrevious studies investigating the perceptual attributes of tactile edge-orientation processing have applied their stimuli to an immobilized fingertip. Here we tested the perceptual attributes of edge orientation processing when participants actively touched the stimulus. Our participants moved their finger over two pairs of edges–one pair parallel and the other nonparallel to varying degrees–and were asked to identify which of the two pairs was nonparallel. In addition to the psychophysical estimates of edge orientation acuity, we measured the speed at which participants moved their finger and the forces they exerted when moving their finger over the stimulus. We report four main findings. First, edge orientation acuity during active touch averaged 12.4°, similar to that previously reported during passive touch. Second, on average, participants moved their finger over the stimuli at 23.9 mm/s and exerted contact forces of 0.47 N. Third, across participants, there was no clear relationship between how people moved their finger or how they pressed on the stimulus and their edge orientation acuity. However, within participants, there appeared to be a weak effect of speed on performance whereby error trials included slightly faster finger movements; no equivalent effect was found for contact force. Fourth, consistent with previous work testing spatial acuity, we found significant correlation between fingertip size and orientation acuity such that people with smaller fingertips tended to have better orientation acuity.
Interspecies DNA acquisition by a naturally competentAcinetobacter baumanniistrain
Authors: Traglia German M. , Place Kori , Dotto Cristian , Fernandez Jennifer S. , Bahiense Camila dos Santos , Soler-Bistue Alfonso , Iriarte Andres , Tolmasky Marcelo E. , Bonomo Robert A , Melano Roberto G. , Ramírez María Soledad 
Published: April 2018

ABSTRACTAcinetobacter baumanniiis a human pathogen that frequently acquires antibiotic resistance genes leading to the emergence of multi-drug-resistant (MDR) strains. To investigate the role of transformation in the acquisition of resistance determinants by this species, the susceptible strain A118 was exposed to genomic DNA of carbapenem-resistantKlebsiella pneumoniae(CRKp). Resistant transformants were obtained and an increase in the resistance level to all β-lactam antibiotics was observed. Whole genome analysis of transformant clones demonstrated the acquisition of CRKp DNA. The most frequently acquired genes correspond to mobile elements, antibiotic resistance genes, and operons involved in metabolism. Bioinformatic analyses andin silicogene flow prediction strengthen our findings, showing that a continuing exchange of genetic material betweenA. baumanniiandK. pneumoniaeoccurs when they share the same niche. Our results reinforce the idea that natural transformation may play a key role in the increasing emergence ofA. baumanniiMDR.IMPORTANCESince the characterization of antibiotic resistance in the late ‘50s, antibiotic resistance propagation was classically associated with horizontal gene transfer (HGT) mediated by plasmids bearing multiple resistance genes. Here we show that, at least in the human pathogenA. baumannii, transformation also plays a major role in the acquisition of antibiotic resistance determinants. This study unravels that at least for certain pathogens the propagation of resistance genes occurs by alternative HGT mechanisms which in the past have been unappreciated.
The lipid droplet protein Pgc1 controls the subcellular distribution of phosphatidylglycerol
Authors: Kubalová Dominika , Veselá Petra , Awadová Thuraya , Daum Günther , Malínský Jan , Balážová Mária 
Published: April 2018

AbstractThe biosynthesis of yeast phosphatidylglycerol (PG) takes place in the inner mitochondrial membrane. Outside mitochondria, the abundance of PG is low. Here we present evidence that the subcellular distribution of PG is maintained by locally controlled enzymatic activity of the PG-specific phospholipase, Pgc1. We document that the Pgc1 absence leads to spreading of PG over various cellular membranes. Fluorescently labeled Pgc1 protein strongly accumulates at the surface of lipid droplets (LD). We show, however, that LD are not only dispensable for Pgc1-mediated PG degradation, but even host no phospholipase activity of Pgc1. Ourin vitroassays document the capability of LD-accumulated Pgc1 to degrade PG upon entry to membranes of the endoplasmic reticulum, mitochondria, and even of artificial phospholipid vesicles. FRAP analysis confirms continuous exchange of GFP-Pgc1 within individual LDin situ, suggesting that a steady-state equilibrium exists between LD and membranes to regulate immediate phospholipase activity of Pgc1. In this model, LD serve as storage place and shelter Pgc1 preventing untimely degradation, while both phospholipase activity and degradation of the enzyme occur in membranes.