bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive Value of FDG PET/CT to Detect Lymph Node Metastases in Cervical Cancer
Authors: Brunette Laurie L. , Bonyadlou Shahram , Ji Lingyun , Groshen Susan , Shuster Dena , Mehta Arjun , Sposto Richard , Matsuo Koji , Lin Yvonne G. , Roman Lynda D. 
Published: August 2018

Purpose
The aim of this study was to determine the prognostic significance of PET/CT findings in women with cervical cancer and describe the normalization of lymph node SUVmax (nSUVmax).

Materials and Methods
A retrospective review was performed of 113 patients with cervical cancer who underwent a PET/CT before receiving definitive therapy. SUVmax measurements were normalized to the SUV of the pelvic blood pool. Patient, tumor, and PET/CT data were correlated to extracervical recurrence-free survival (ecRFS) and lymph node pathology.

Results
Of 113 patients, there were 23 (20%) extracervical recurrences. On univariate analysis, stage, histology, nSUVmax, and radiographic size of the primary tumor, and nSUVmax of the most hypermetabolic lymph node were significantly associated with ecRFS. On multivariable analysis, nSUVmax and radiographic size of the primary tumor remained associated with ecRFS (both P < 0.001). Sixty-six patients underwent pelvic, common iliac, and/or para-aortic nodal sampling. The sensitivity, specificity, false-negative, and false-positive rates of PET/CT for lymph node metastases were 53%, 75%, 6%, and 82%, respectively. On univariate analysis, nSUVmax, and radiographic size of the primary tumor, and nSUVmax of the most hypermetabolic lymph node, and radiographic size of the largest lymph node, were associated with the presence of at least one pathologically positive lymph node. On multivariable analysis, only the radiographic size of the largest lymph node remained significantly associated with lymph node metastases (P < 0.001).

Conclusions
The size and nSUVmax of the primary tumor were associated with ecRFS. PET/CT has a low false-negative rate but high false-positive rate for lymph node metastases.
Mycoplasma genitaliumincidence, persistence, concordance between partners and progression: systematic review and meta-analysis
Authors: Cina Manuel , Baumann Lukas , Egli-Gany Dianne , Halbeisen Florian S , Ali Hammad , Scott Pippa , Low Nicola 
Published: August 2018

ABSTRACTBackgroundMycoplasma genitaliumis increasingly seen as an emerging sexually transmitted pathogen, and has been likened toChlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determineM. genitaliumincidence, persistence, concordance between sexual partners, and the risk of pelvic inflammatory disease (PID).MethodsWe searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies.ResultsWe screened 4634 records and included 17 studies; five (4100 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI, 0.61 to 1.53, I2 0%). Median persistence ofM. genitaliumwas estimated from one to three months in four studies but 15 months in one study. In ten studies measuringM. genitaliuminfection status in couples, 39-50% of male or female sexual partners of infected participants also hadM. genitaliumdetected. In prospective studies, the incidence of PID was higher in women withM. genitaliumthan those without (RR 1.68, 95% CI 0.59 to 2.77, I20%, 2 studies).DiscussionBased on findings from this and our linked review of prevalence, concordantM. genitaliummight be less common than forC. trachomatisand the age distributions of the infections differ. The synthesised data about prevalence, incidence and persistence ofM. genitaliuminfection are inconsistent. Taken together with evidence about antimicrobial resistance in the two infections,M. genitaliumis not the new chlamydia.Registration NumbersPROSPERO: CRD42015020420, CRD42015020405KEY MESSAGESThere are calls for widespread screening forMycoplasma genitalium, but the natural history of this emerging sexually transmitted pathogen is poorly understood.M. genitaliumincidence was 1.07 (95% confidence intervals, CI 0.61 to 1.53) per 100-person years in women in highly developed countries, 39-50% of infected individuals had a heterosexual partner withM. genitaliumand the risk ratio for pelvic inflammatory disease was 1.68 (95% CI 0.59 to 2.77).The duration of untreatedM. genitaliuminfection is probably longer than persistent detection ofM. genitalium, as measured in most cohort studies, in which inadvertent treatment cannot be ruled out.The results of this systematic review and other evidence sources show important differences in the epidemiology and dynamics ofM. genitaliumandChlamydia trachomatisinfection.
Self-organization controls expression more than abundance of molecular components of transcription and translation in confined cell-free gene expression
Authors: Caveney P.M. , Dabbs R. , Chauhan G. , Norred S.E. , Collier C.P. , Abel S.M. , Simpson M.L. 
Published: August 2018

AbstractCell-free gene expression using purified components or cell extracts has become an important platform for synthetic biology that is finding a growing numBer of practical applications. Unfortunately, at cell-relevant reactor volumes, cell-free expression suffers from excessive variability (noise) such that protein concentrations may vary by more than an order of magnitude across a population of identically constructed reaction chambers. Consensus opinion holds that variability in expression is due to the stochastic distribution of expression resources (DNA, RNAP, ribosomes, etc.) across the population of reaction chambers. In contrast, here we find that chamber-to-chamber variation in the expression efficiency generates the large variability in protein production. Through analysis and modeling, we show that chambers self-organize into expression centers that control expression efficiency. Chambers that organize into many centers, each having relatively few expression resources, exhibit high expression efficiency. Conversely, chambers that organize into just a few centers where each center has an abundance of resources, exhibit low expression efficiency. A particularly surprising finding is that diluting expression resources reduces the chamber-to-chamber variation in protein production. Chambers with dilute pools of expression resources exhibit higher expression efficiency and lower expression noise than those with more concentrated expression resources. In addition to demonstrating the means to tune expression noise, these results demonstrate that in cell-free systems, self-organization may exert even more influence over expression than the abundance of the molecular components of transcription and translation. These observations in cell-free platform may elucidate how self-organized, membrane-less structures emerge and function in cells.
Nucl2Vec : Local alignment of DNA sequences using Distributed Vector Representation
Authors: Ganesh Prakhar , Gupta Gaurav , Saini Shubhi , Paul Kolin 
Published: August 2018

AbstractThe Next Generation Sequencing Technique (NGS) has provided affordable and fast method for generating genetic data. Generation of whole Genome Sequence and extract relevant information from this data is still a computationally expensive process. In this paper we demonstrate a novel approach for local alignment of DNA reads with respect to reference genome. For this process we have used Skip-gram model for creating encoding(Nucl2Vec) and k-nearest neighbor for the alignment. With our new approach we have reduced computation cost for local alignment, while achieving accuracy comparable to existing defacto standard BWA-MEM tool.Index TermsGenome, Alignment, Local Alignment, k-nearest Neighbor, Distributed vector representation, Skip-gram
Homozygous TRPV4 mutation causes congenital distal spinal muscular atrophy and arthrogryposis
Authors: Velilla Jose , Marchetti Michael Mario , Toth-Petroczy Agnes , Grosgogeat Claire , Bennett Alexis H , Carmichael Nikkola , Estrella Elicia , Darras Basil T. ,   Brigham Genomic Medicine, Frank Natasha Y , Krier Joel , Gaudet Rachelle , Gupta Vandana A. 
Published: August 2018

AbstractObjectiveThe objective of this study is to identify the genetic cause of disease in a congenital form of congenital spinal muscular atrophy and arthrogryposis (CSMAA).MethodsA 2-year-old boy was diagnosed with arthrogryposis multiplex congenita, severe skeletal abnormalities, torticollis, vocal cord paralysis and diminished lower limb movement. Whole exome sequencing was performed on the proband and family members. In silico modeling of protein structure and heterologous protein expression and cytotoxicity assays were performed to validate pathogenicity of the identified variant.ResultsWhole exome sequencing revealed a homozygous mutation in the TRPV4 gene (c.281C>T; p.S94L). The identification of a recessive mutation in TRPV4 extends the spectrum of mutations in recessive forms of the TRPV4-associated disease. p.S94L and other previously identified TRPV4 variants in different protein domains were compared in structural modeling and functional studies. In silico structural modeling suggests that the p.S94L mutation is in the disordered N-terminal region proximal to important regulatory binding sites for phosphoinositides and for PACSIN3, which could lead to alterations in trafficking and/or channel sensitivity. Functional studies by western blot and immunohistochemical analysis show that p.S94L reduces TRPV4 protein stability because of increased cytotoxicity and therefore involves a gain-of-function mechanism.ConclusionThis study identifies a novel homozygous mutation in TRPV4 as a cause of the recessive form of congenital spinal muscular atrophy and arthrogryposis.
Proton co-transport and voltage dependence enforce unidirectional metal transport in an Nramp transporter
Authors: Bozzi Aaron T. , Bane Lukas B. , Zimanyi Christina M. , Gaudet Rachelle 
Published: August 2018

AbstractSecondary transporters harness electrochemical energy to move substrate through structurally-enforced co-substrate “coupling”. We untangle the “proton-metal coupling” behavior by a Natural resistance-associated macrophage protein (Nramp) transporter into two distinct phenomena: ΔpH stimulation of metal transport and metal stimulation of proton co-transport. Surprisingly, metal type dictates co-transport stoichiometry, leading to manganese-proton symport but cadmium uniport. Additionally, the membrane potential affects both the kinetics and thermodynamics of metal transport. A conserved salt-bridge network near the metal-binding site imparts voltage dependence and enables proton co-transport, properties that allow this Nramp transporter to maximize metal uptake and prevent deleterious back-transport of acquired metals. We provide a new mechanistic model for Nramp metal-proton symport in which, in addition to substrate gradients determining directionality as in canonical secondary transport, synergy between protein structure and physiological voltage enforces unidirectional substrate movement. Our results illustrate a functional advantage that arises from deviations from the traditional model of symport.
Estimation of Rearrangement Break Rates Across the Genome
Authors: Hann-Soden Christopher , Holmes Ian , Taylor John W. 
Published: August 2018

AbstractGenomic rearrangements provide an important source of novel functions by recombining genes and motifs throughout and between genomes. However, understanding how rearrangement functions to shape genomes is hard because reconstructing rearrangements is a combinatoric problem which often has many solutions. In lieu of reconstructing the history of rearrangements, we answer the question of where rearrangements are occurring in the genome by remaining agnostic to the types of rearrangement and solving the simpler problem of estimating the rate at which double-strand breaks occur at every site in a genome. We phrase this problem in graph theoretic terms and find that it is a special case of the minimum cover problem for an interval graph. We employ and modify existing algorithms for efficiently solving this problem. We implement this method as a Python program, named BRAG, and use it to estimate the break rates in the genome of the model Ascomycete mold,Neurospora crassa. We find evidence that rearrangements are more common in the subtelomeric regions of the chromosomes, which facilitates the evolution of novel genes.
Avian diet and foraging ecology constrain foreign egg recognition and rejection
Authors: Luro Alec B. , Hauber Mark E. 
Published: August 2018

AbstractEgg rejection is the most common defense against avian brood parasitism in which the host either removes the parasitic egg or deserts the parasitized clutch. The ability to recognize and reject a parasitic egg depends on bill morphology, sensory systems, and cognition, all of which are also shaped by other selective processes, such as foraging. This begs the question whether specific phenotypes associated with different foraging strategies and diets may constrain or facilitate egg recognition and rejection. Here, we propose a novel hypothesis that host species phenotypes related to foraging ecology and diet impose morphological and sensory constraints on the evolution of egg rejection. We conducted a comparative analysis of the adult diets and egg rejection rates of 165 current host and non-host species and found species that consume an animal and fruit dominated diet rather than seeds and grains, forage arboreally rather than aerially, and possess relatively larger body sizes have significantly higher egg rejection rates. As predicted, these results suggest that phenotypes related to specific diets and foraging strategies may differentially constrain or facilitate evolution of host egg rejection defenses against avian brood parasitism.
Deformation microscopy for dynamic intracellular and intranuclear mapping of mechanics with high spatiotemporal resolution
Authors: Ghosh Soham , Seelbinder Benjamin , Henderson Jonathan T. , Watts Ryan D. , Veress Alexander I. , Neu Corey P. 
Published: August 2018

AbstractStructural heterogeneity is a hallmark of living cells and nuclei that drives local mechanical properties and dynamic cellular responses, including adhesion, gene expression, and differentiation. However, robust quantification of intracellular or intranuclear mechanics are lacking from conventional methods. Here, we describe new development of deformation microscopy that leverages conventional imaging and an automated hyperelastic warping algorithm to investigate strain history, deformation dynamics, and changes in structural heterogeneity within the interior of cells and nuclei. Using deformation microscopy, we found that tensile loading modes dominated intranuclear architectural dynamics in cardiomyocytes in vitro or myocytes in vivo, which was compromised by disruption of LINC complex molecule nesprin-3 or Lamin A/C, respectively. We also found that cells cultured on stiff substrates or in hyperosmotic conditions displayed abnormal strain burden and asymmetries compared to controls at interchromatin regions where active translation was expected. Deformation microscopy represents a foundational approach toward intracellular elastography, with potential utility to provide new mechanistic and quantitative insights in diverse mechanobiological applications.
Paranoid schizophrenia and methamphetamine-induced paranoia are both characterized by a similar LINE-1 partial methylation profile, which is more pronounced in paranoid schizophrenia
Authors: Kalayasiri Rasmon , Kraijak Korakot , Mutirangura Apiwat , Maes Michael 
Published: August 2018

AbstractBackgroundThere is evidence that schizophrenia is a neuro-immune disorder. Genes linked to intragenic LINE-1 methylation show a strong association with immune-associated disorders including psychosis. The aim of this study was to examine LINE-1 methylation patterns in paranoid schizophrenia and methamphetamine-induced paranoia, a model for schizophrenia.MethodsThis study recruited 31 patients with paranoid schizophrenia, 94 with methamphetamine-induced paranoia (MIP) and 163 normal controls. LINE-1 methylation patterns were assayed in peripheral blood mononuclear cells and a combined bisulphite restriction analysis and COBRA were used to estimate global methylation (mC) and LINE-1 CpG dinucleotide methylation patterns, namely 2 methylated (mCmC) and 2 unmethylated (uCuC) CpGs and the partially methylated loci mCuC (5’m with 3’u) and uCmC (5’u with 3’m).ResultsPatients with paranoid schizophrenia show highly significant changes in LINE-1 partial methylation patterns, namely a higher % mCuC and lower % uCmC as compared with controls and MIP patients, while the latter show higher % mCuC but lower % uCmC as compared with controls. Higher % mCuC significantly predicts paranoid schizophrenia with a sensitivity of 51.6%, specificity of 97.5% and an area under the ROC curve of 0.895.ConclusionsThe results indicate that a common dysfunction in LINE-1 partial methylation may underpin both paranoid schizophrenia and MIP and that this methylation pattern is significantly more expressed in paranoid schizophrenia than MIP. Reciprocal links between impairments in LINE-1 methylation and neuro-immune and neuro-oxidative pathways may underpin the pathophysiology of both MIP and paranoid schizophrenia.
In vivo function of the lipid raft protein Flotillin 1 during CD8+ T cell-mediated host surveillance
Authors: Ficht Xenia , Ruef Nora , Stolp Bettina , Moalli Federica , Page Nicolas , Merkler Doron , Nichols Ben J. , Diz-Muñoz Alba , Niggli Verena , Stein Jens V. 
Published: August 2018

AbstractFlotillin-1 (Flot1) is a highly conserved, ubiquitously expressed lipid raft-associated scaffolding protein. Migration of Flot1-deficient neutrophils is impaired due to a decrease in myosin II-mediated contractility. Flot1 also accumulates in the uropod of polarized T cells, suggesting an analogous role in T cell migration. Here, we analyzed morphology and migration of naïve and memory WT and Flot1-/- CD8+ T cells in lymphoid and non-lymphoid tissues with intravital two-photon microscopy, as well as their clonal expansion during antiviral immune responses. Flot1-/- CD8+ T cells displayed minor alterations in cell shape and motility parameters in vivo but showed comparable homing to lymphoid organs and infiltration into non-lymphoid tissues. Taken together, Flot1 plays a detectable but unexpectedly minor role for CD8+ T cell behavior under physiological conditions.
Neighbor signals perceived by phytochrome B increase thermotolerance in Arabidopsis
Authors: Arico Denise , Legris Martina , Castro Luciana , Garcia Carlos Fernando , Laino Aldana , Casal Jorge , Mazzella Maria Agustina 
Published: August 2018

AbstractDue to the preeminence of reductionist approaches, our understanding of plant responses to combined stresses is limited. We speculated that light-quality signals of neighboring vegetation might increase susceptibility to heat shocks because shade reduces tissue temperature and hence the likeness of heat shocks. In contrast, plants ofArabidopsis thalianagrown under low red / far-red ratios typical of shade were less damaged by heat stress than plants grown under simulated sunlight. Shade reduces the activity of phytochrome B (phyB) and thephyBmutant showed high tolerance to heat stress even under simulated sunlight. The enhanced heat tolerance under low red / far-red ratios failed in a multiple mutant of PHYTOCHROME INTERACTING FACTORs. ThephyBmutant showed reduced expression of several fatty acid desaturase (FAD) genes, proportion of fully unsaturated fatty acids and electrolyte leakage of membranes exposed to a heat shock. Activation of phyB by red light also reduced thermotolerance of dark-grown (etiolated) seedlings but not via changes inFADgene expression and membrane stability. We propose that the reduced photosynthetic capacity linked to thermotolerant membranes would be less costly under shade, where the light input itself limits photosynthesis.
Inpatient mobility to predict hospital-onset Clostridium difficile: a network approach
Authors: Bush Kristen , Barbosa Hugo , Farooq Samir , Weisenthal Samuel J. , Trayhan Melissa , White Robert J. , Ghoshal Gourab , Zand Martin S. 
Published: August 2018

AbstractWith hospital-onset Clostridium difficile Infection (CDI) still a common occurrence in the U.S., this paper examines the relationship between unit-wide CDI susceptibility and inpatient mobility and creates a predictive measure of CDI called “Contagion Centrality”. A mobility network was constructed using two years of patient electronic health record (EHR) data within a 739-bed hospital (Jan. 2013 - Dec. 2014; n=72,636 admissions). Network centrality measures were calculated for each hospital unit (node) providing clinical context for each in terms of patient transfers between units (edges). Daily unit-wide CDI susceptibility scores were calculated using logistic regression and compared to network centrality measures to determine the relationship between unit CDI susceptibility and patient mobility. Closeness centrality was a statistically significant measure associated with unit susceptibility (p-value < 0.05), highlighting the importance of incoming patient mobility in CDI prevention at the unit-level. Contagion Centrality (CC) was calculated using incoming inpatient transfer rates, unit-wide susceptibility of CDI, and current hospital CDI infections. This measure is statistically significant (p-value <0.05) with our outcome of hospital-onset CDI cases, and captures the additional opportunities for transmission associated with inpatient transfers. We have used this analysis to create an easily interpretable and informative clinical tool showing this relationship and risk of hospital-onset CDI in real-time. Quantifying and visualizing the combination of inpatient transfers, unit-wide risk, and current infections help identify hospital units at risk of developing a CDI outbreak, and thus provide clinicians and infection prevention staff with advanced warning and specific location data to concentrate prevention efforts.