bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can cancer GWAS variants modulate immune cells in the tumor microenvironment?
Authors: Zhang Yi , Manjunath Mohith , Yan Jialu , Baur Brittany A. , Zhang Shilu , Roy Sushmita , Song Jun S. 
Published: December 2018

AbstractGenome-wide association studies (GWAS) have hitherto identified several genetic variants associated with cancer susceptibility, but the molecular functions of these risk modulators remain largely uncharacterized. Recent studies have begun to uncover the regulatory potential of non-coding GWAS SNPs by using epigenetic information in corresponding cancer cell types and matched normal tissues. However, this approach does not explore the potential effect of risk germline variants on other important cell types that constitute the microenvironment of tumor or its precursor. This paper presents evidence that the breast cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor infiltrating lymphocytes. CTSW is a candidate tumor-suppressor gene, with expression highly specific to immune cells and also positively correlated with breast cancer patient survival. Integrative analyses suggest a putative causative variant in a GWAS-linked enhancer in lymphocytes that loops to the 3’ end of CTSW through three-dimensional chromatin interaction. Our work thus poses the possibility that a cancer-associated genetic variant might regulate a gene not only in the cell of cancer origin, but also in immune cells in the microenvironment, thereby modulating the immune surveillance by T lymphocytes and natural killer cells and affecting the clearing of early cancer initiating cells.
Dynamic 11C-PiB PET shows cerebrospinal fluid flow alterations in Alzheimer’s disease and multiple sclerosis
Authors: Schubert Julia J. , Veronese Mattia , Marchitelli Livia , Bodini Benedetta , Tonietto Matteo , Stankoff Bruno , Brooks David J. , Bertoldo Alessandra , Edison Paul , Turkheimer Federico E. 
Published: December 2018

AbstractCerebrospinal fluid (CSF) plays an important role in the clearance of solutes and maintenance of brain homeostasis. 11C-PiB PET was recently proposed as a tool for detection of CSF clearance alterations in Alzheimer’s disease. The current study seeks to investigate the magnitude of 11C-PiB PET signal in the lateral ventricles of an independent group of Alzheimer’s and mild cognitive impairment subjects. We have also evaluated multiple sclerosis as a model of disease with CSF clearance alterations without amyloid-beta tissue accumulation.MethodsA set of Alzheimer’s and mild cognitive impairment subjects and a set of multiple sclerosis subjects with matched healthy controls underwent MRI and dynamic 11C-PiB PET. Manual lateral ventricle regions of interest were generated from MRI data. PET data was analysed using a simplified reference tissue model with cerebellum or a supervised reference region, for the Alzheimer’s and multiple sclerosis datasets, respectively. Magnitude of 11C-PiB signal in the lateral ventricles was calculated as area under curve from 35 to 80 minutes and standard uptake value ratio (SUVR) from 50 to 70 minutes. Compartmental modelling analysis was performed on a separate dataset containing Alzheimer’s and matched healthy control data with an arterial input function to further understand the kinetics of the lateral ventricular 11C-PiB signal.ResultsAnalysis of variance revealed significant group differences in lateral ventricular SUVR across the Alzheimer’s, mild cognitive impairment, and healthy control groups (p=0.004). Additional pairwise comparisons revealed significantly lower lateral ventricular SUVR in Alzheimer’s compared to healthy controls (p<0.001) and mild cognitive impairment (p=0.029). Lateral ventricular SUVR was also significantly lower in multiple sclerosis compared to healthy controls (p=0.008). Compartmental modelling analysis revealed significantly lower uptake rates of 11C-PiB signal from blood (p=0.005) and brain tissue (p=0.004) to the lateral ventricles in Alzheimer’s compared to healthy controls. This analysis also revealed significantly lower clearance of 11C-PiB signal out of the lateral ventricles in Alzheimer’s compared to healthy controls (p=0.002).ConclusionOverall, these results indicate that dynamic 11C-PiB PET can be used to observe pathological changes in cerebrospinal fluid dynamics and that cerebrospinal fluid-mediated clearance is reduced in Alzheimer’s disease and multiple sclerosis compared to healthy controls.
Forecasting when cells die during antibiotic exposure using stochastic gene expression
Authors: Rossi Nicholas A. , Meouche Imane El , Dunlop Mary J. 
Published: December 2018

AbstractAntibiotic killing does not occur at a single, precise time for all cells within a population. Variability in time to death can be caused by stochastic expression of genes, resulting in differences in endogenous stress-resistance levels between individual cells in a population. This variability can be part of a bet-hedging strategy where cells leverage noise to ensure a subset of the population can tolerate the drug, while decreasing the overall cost of expressing resistance genes. We asked whether single-cell differences in gene expression prior to antibiotic addition were related to cell survival times after antibiotic exposure for a range of genes of diverse function. We quantified the time to death of single cells under antibiotic exposure in combination with expression of reporters. For some reporters, the time to cell death had a strong relationship with the initial expression level of the genes. Reporters that could forecast cell fate included stress response genes, but also genes involved in a variety of other cellular processes like metabolism. Our results highlight the single-cell level non-uniformity of antibiotic killing and also provide examples of key genes where cell-to-cell variation in expression prior to antibiotic exposure is strongly linked to extended durations of antibiotic survival.
svtools: population-scale analysis of structural variation
Authors: Larson David E. , Abel Haley J. , Chiang Colby , Badve Abhijit , Das Indraniel , Eldred James M. , Layer Ryan M. , Hall Ira M. 
Published: December 2018

ABSTRACTSummaryLarge-scale human genetics studies are now employing whole genome sequencing with the goal of conducting comprehensive trait mapping analyses of all forms of genome variation. However, methods for structural variation (SV) analysis have lagged far behind those for smaller scale variants, and there is an urgent need to develop more efficient tools that scale to the size of human populations. Here, we present a fast and highly scalable software toolkit (svtools) and cloud-based pipeline for assembling high quality SV maps – including deletions, duplications, mobile element insertions, inversions, and other rearrangements – in many thousands of human genomes. We show that this pipeline achieves similar variant detection performance to established per-sample methods (e.g., via LUMPY), while providing fast and affordable joint analysis at the scale of ≥100,000 genomes. These tools will help enable the next generation of human genetics studies.Availability and Implementationsvtools is implemented in Python and freely available (MIT) fromhttps://github.com/hall-lab/svtools.Contactihall@wustl.edu
Swapping Birth and Death: Symmetries and Transformations in Phylodynamic Models
Authors: Stadler Tanja , Steel Mike 
Published: December 2018

AbstractStochastic birth–death models provide the foundation for studying and simulating evolutionary trees in phylodynamics. A curious feature of such models is that they exhibit fundamental symmetries when the birth and death rates are interchanged. In this paper, we explain and formally derive these transformational symmetries. We also show that these transformational symmetries (encoded in algebraic identities) are preserved even when taxa at the present are sampled with some probability. However, these extended symmetries require the death rate parameter to sometimes take a negative value. In the last part of this paper, we describe the relevance of these transformations and their application to computational phylodynamics, particularly to maximum likelihood and Bayesian inference methods, as well as to model selection. Phylodynamics, phylogenetics, speciation-extinction models, birth-death models, algebraic symmetries, maximum likelihood, Bayesian inference
Cheaters shape the evolution of phenotypic heterogeneity in Bacillus subtilis biofilms
Authors: Martin Marivic , Dragoš Anna , Otto Simon B. , Schäfer Daniel , Brix Susanne , Maróti Gergely , Kovács Ákos T. 
Published: December 2018

ABSTRACTBiofilms are closely packed cells held and shielded by extracellular matrix composed of structural proteins and exopolysaccharides (EPS). As matrix components are costly to produce and shared within the population, EPS-deficient cells can act as cheaters by gaining benefits from the cooperative nature of EPS producers. Remarkably, genetically programmed EPS producers can also exhibit phenotypic heterogeneity at single cell level. Previous studies have shown that spatial structure of biofilms limits the spread of cheaters, but the long-term influence of cheating on biofilm evolution is not well understood. Here, we examine the influence of EPS non-producers on evolution of matrix production within the populations of EPS producers in a model biofilm-forming bacterium, Bacillus subtilis. We discovered that general adaptation to biofilm lifestyle leads to an increase in phenotypical heterogeneity of eps expression. Apparently, prolonged exposure to EPS-deficient cheaters, may result in different adaptive strategy, where eps expression increases uniformly within the population. We propose a molecular mechanism behind such adaptive strategy and demonstrate how it can benefit the EPS-producers in the presence of cheaters. This study provides additional insights on how biofilms adapt and respond to stress caused by exploitation in long-term scenario.
Consistent alterations of human fecal microbes after transplanted to germ-free mice
Authors: Li Yanze , Cao Wenming , Gao Na L , Zhao Xing-Ming , Chen Wei-Hua 
Published: December 2018

AbstractBackgroundFecal microbiota transplant (FMT) of human fecal samples to germ-free (GF) mice is useful for establishing causal relationships between gut microbiota and human phenotypes. However, due to intrinsic differences between human and mouse intestines and distinct diets between the two organisms, replicating human phenotypes in mouse through FMT is not guaranteed; similarly, treatments that are effective in mouse models do not guarantee their success in human either.ResultsIn this study, we aimed to identify human gut microbes that have undergone significant and consistent changes after transplanted to GF mice across multiple experimental settings. By comparing gut microbiota profiles in 1,713 human-mouse pairs, we found strikingly on average <50% of the human gut microbes can be re-established in mice at the species level; among which, more than 1/3 have undergone significant changes (referred as to “variable microbes”), most of which were consistent across multiple human-mouse pairs and experimental settings. Consistently, one-third of human samples had changed their enterotypes, i.e. significant changes in their leading species after FMT. Mice fed with controlled diet showed significant decrease in the enterotype change rate (~25%) as compared those with non-controlled diet (~50%), suggesting a possible solution for rescue. Strikingly, most of the variable microbes have been implicated in human diseases, with some being recognized as causing species.ConclusionsOur results highlighted the challenges of using mouse model in replicating human gut microbiota-associated phenotypes, provided useful information for researchers using mice in their gut microbiota studies and call for additional validations after FMT.
ECT2 associated to PRICKLE1 are poor-prognosis markers in triple-negative breast cancer
Authors: Daulat Avais M. , Finetti Pascal , Revinski Diego , Wagner Mônica Silveira , Camoin Luc , Audebert Stéphane , Birnbaum Daniel , Kodjabachian Laurent , Borg Jean-Paul , Bertucci François 
Published: December 2018

AbstractBackgroundTriple-negative breast cancers are poor-prognosis tumors characterized by absence of molecular signature and are chemotherapy is still the only systemic treatment. Currently, research focus to identify biomarkers that may be usable for prognosis and/or for treatment, notably among the proteins involved in cell migration and metastatic capacity.MethodsWe used proteomic approach to identify protein complexes associated to PRICKLE1 and the mRNA expression level of the corresponding genes in a retrospective series of 8,982 clinically annotated patients with invasive primary breast cancer were assessed. Then, we characterize molecularly the interaction between PRICKLE1 and the guanine nucleotide exchange factor ECT2. Finally, experiments in Xenopus have been carrying out to determine their evolutionary conserved interaction.ResultsWe have identified a network of proteins interacting with the prometastatic scaffold protein PRICKLE1 that includes several small G-protein regulators involved in cell migration and metastasis. Combined analysis expression of PRICKLE1 and small G-protein regulators expression has a strong prognostic value in TNBC. We show that PRICKLE1 controls the activity of ECT2 on RAC1 signaling, a pathway required for cancer cell dissemination.ConclusionsThis work supports the idea that promigratory proteins, which are overexpressed in cancerous epithelium, are suitable pharmaceutical targets.
Evolution of regulatory networks associated with traits under selection in cichlids
Authors: Mehta Tarang K. , Koch Christopher , Nash Will , Knaack Sara A. , Sudhakar Padhmanand , Olbei Marton , Bastkowski Sarah , Penso-Dolfin Luca , Korcsmaros Tamas , Haerty Wilfried , Roy Sushmita , Di-Palma Federica 
Published: December 2018

AbstractSeminal studies of vertebrate protein evolution speculated that gene regulatory changes can drive anatomical innovations. However, very little is still known about gene regulatory network (GRN) evolution associated with phenotypic effect across ecologically-diverse species. Using a novel approach to reconstruct GRNs in vertebrate species, we aimed to study GRN evolution in representative species of the most striking example of an adaptive radiation, the East African cichlids. We previously demonstrated how the explosive phenotypic diversification of East African cichlids is attributed to diverse molecular mechanisms, including accelerated regulatory sequence evolution and gene expression divergence. To investigate these mechanisms across species at a genome-wide scale, our novel network-based approach identifies ancestral and extant gene co-expression modules along a phylogeny, and by integrating associated regulators, predicts candidate regulatory regions implicated in traits under selection in cichlids. As a case study, we present data from a well-studied adaptive trait - the visual system - for which we report striking cases of network rewiring for visual opsin genes, identify discrete regulatory variants, and investigate the plausibility of their association with cichlid visual system evolution. In regulatory regions of visual opsin genes,in vitroassays confirm that transcription factor binding site mutations disrupt regulatory edges across species, and segregate according to lake species phylogeny and ecology, suggesting GRN rewiring in radiating cichlids. Our approach revealed numerous novel potential candidate regulatory regions across cichlid genomes with no prior association, as well as those with previously reported associations to known adaptive evolutionary traits, thus providing proof of concept.
‘Chromatic’ Neuronal Jamming in a Primitive Brain
Authors: Khariton Margarita , Kong Xian , Qin Jian , Wang Bo 
Published: December 2018

ABSTRACTJamming models developed in inanimate matter have been widely used to describe cell packing in tissues1–7, but predominantly neglect cell diversity, despite its prevalence in biology. Most tissues, animal brains in particular, comprise a mix of many cell types, with mounting evidence suggesting that neurons can recognize their respective types as they organize in space8–11. How cell diversity revises the current jamming paradigm is unknown. Here, in the brain of the flatworm planarian Schmidtea mediterranea, which exhibits remarkable tissue plasticity within a simple, quantifiable nervous system12–16, we identify a distinct packing state, ‘chromatic’ jamming. Combining experiments with computational modeling, we show that neurons of distinct types form independent percolating networks barring any physical contact. This jammed state emerges as cell packing configurations become constrained by cell type-specific interactions and therefore may extend to describe cell packing in similarly complex tissues composed of multiple cell types.
Refining the pneumococcal competence regulon by RNA-sequencing
Authors: Slager Jelle , Aprianto Rieza , Veening Jan-Willem 
Published: December 2018

ABSTRACTCompetence for genetic transformation allows the opportunistic human pathogenStreptococcus pneumoniaeto take up exogenous DNA for incorporation into its own genome. This ability may account for the extraordinary genomic plasticity of this bacterium, leading to antigenic variation, vaccine escape, and the spread of antibiotic resistance markers. The competence system has been thoroughly studied and its regulation is well-understood. Additionally, over the last decade, several stress factors have been shown to trigger the competent state, leading to the activation of several stress response regulons. The arrival of next-generation sequencing techniques allowed us to update the competence regulon, the latest report of which still depended on DNA microarray technology. Enabled by the availability of an up-to-date genome annotation, including transcript boundaries, we assayed time-dependent expression of all annotated features in response to competence induction, were able to identify the affected promoters and produced a more complete overview of the various regulons activated during competence. We show that 4% of all annotated genes are under direct control of competence regulators ComE and ComX, while the expression of a total of up to 17% of all genes is, either directly or indirectly, affected. Among the affected genes are various small RNAs with an as-of-yet unknown function. Besides the ComE and ComX regulons, we were also able to refine the CiaR, VraR (LiaR) and BlpR regulons, underlining the strength of combining RNA-seq with a well-annotated genome.
A statistical method for build orientation determination in additive manufacturing
Authors: Zhang Yicha , Harik Ramy , Fadel Georges , Bernard Alain 
Published: December 2018

Purpose
For part models with complex shape features or freeform shapes, the existing build orientation determination methods may have issues, such as difficulty in defining features and costly computation. To deal with these issues, this paper aims to introduce a new statistical method to develop fast automatic decision support tools for additive manufacturing build orientation determination.

Design/methodology/approach
The proposed method applies a non-supervised machine learning method, K-Means Clustering with Davies–Bouldin Criterion cluster measuring, to rapidly decompose a surface model into facet clusters and efficiently generate a set of meaningful alternative build orientations. To evaluate alternative build orientations at a generic level, a statistical approach is defined.

Findings
A group of illustrative examples and comparative case studies are presented in the paper for method validation. The proposed method can help production engineers solve decision problems related to identifying an optimal build orientation for complex and freeform CAD models, especially models from the medical and aerospace application domains with much efficiency.

Originality/value
The proposed method avoids the limitations of traditional feature-based methods and pure computation-based methods. It provides engineers a new efficient decision-making tool to rapidly determine the optimal build orientation for complex and freeform CAD models.
Use of video microsurgery platform in microsurgical subinguinal varicocelectomy with indocyanine green angiography
Authors: Cho Chak‐Lam , Chu Ringo Wing‐Hong 
Published: December 2018

AimThe aim of the present study was to evaluate the feasibility of the use of the video microsurgery platform and fluorescence imaging exoscope system for microsurgical subinguinal varicocoelectomy (MSV) with intraoperative indocyanine green angiography (ICGA).Patients and MethodsTwo patients with three varicoceles had MSV and intraoperative ICGA performed in August 2018. A video telescopic operating microscope (VITOM) 3‐D system and a VITOM II ICG system were connected to a modular FULL HD IMAGE1 S camera platform. Both telescopes were mounted for convenient positioning and switch between the telescopes.ResultsThe VITOM 3‐D system provided excellent, high‐definition image quality and anatomical details necessary for the procedure of MSV. The system offered a more ergonomic working environment for the operating surgeons. The addition of VITOM II ICG system allowed intraoperative ICGA for better identification of the testicular artery. Testicular arteries were clearly identified and preserved. The setup with holding arms and a camera platform facilitated quick switch between the video systems.ConclusionsThe procedure of MSV with intraoperative ICGA can be performed efficiently with the utilization of the video microsurgery platform.
Development and Psychometric Evaluation of a Brief Approach and Avoidance of Alcohol Questionnaire
Authors: Levine Jacob A. , Noyes Emily T. , Gius Becky K. , Ahlich Erica , Rancourt Diana , Houston Rebecca J. , Schlauch Robert C. 
Published: December 2018

BackgroundThe Approach and Avoidance of Alcohol Questionnaire (AAAQ) was developed as a measure of craving to assess both desires to consume and desires to avoid consuming alcohol. Although the measure has been used in a variety of populations to predict future alcohol use behavior, the factor structures observed vary based on sample type (e.g., clinical vs. college samples) and may be overly long for use in repeated measures designs. The current article describes the development of a brief version of theAAAQfor use in clinical populations.MethodsUsing existing data sets of individuals in treatment for alcohol use disorder, exploratory analyses (e.g., exploratory factor analysis and item response theory) were conducted using an inpatient sample (N = 298) at a substance abuse treatment facility. Confirmatory analyses (e.g., confirmatory factor analysis and multiple regression) were conducted using an inpatient detoxification sample (N = 175) and a longitudinal outpatient treatment sample (N = 53).ResultsThe briefAAAQhad comparable internal consistency, explained a similar amount of variance in alcohol consumption and related problems, and exhibited superior model fit as compared to the original measure.ConclusionsThese findings indicate that the briefAAAQis an effective tool to assess alcohol craving in clinical populations in treatment settings.
Indocyanine green‐enhanced fluorescence‐guided video‐assisted axillary surgery for chronic lymphocele
Authors: Mazza Marco , Sommariva Antonio 
Published: December 2018

AbstractIntroductionLymphocele occurs frequently after regional lymph node dissection. Surgery with multiple lymphatic ligation represents the only reliable treatment for long‐standing chronic lymphocele.Materials and Surgical TechniqueWe report the case of a man with chronic axillary seroma after axillary lymphadenectomy for melanoma. The lymphocele was unresponsive to conservative management and successfully treated with indocyanine green lymphography‐guided video‐assisted axillary surgery.DiscussionIndocyanine green‐enhanced fluorescence video‐assisted identification and ligation of lymph vessels can simply and effectively treat recurrent chronic lymphocele after axillary or groin lymphadenectomy.