bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microtia in a Chinese Specialty Clinic Population: Clinical Heterogeneity and Associated Congenital Anomalies
Authors: Zhang Ye , Jiang Haiyue , Yang Qinghua , He Leren , Yu Xiaobo , Huang Xueshuang , Wu Rongwei , Yang Meirong , Li Chuan , Pan Bo 
Published: November 2018

Background:
Microtia is a congenital anomaly of the external ear that can appear in isolation or in association with other congenital anomalies. In this study, the authors identify the prevalence and phenotypes of associated congenital malformations in patients with microtia in a Chinese specialty clinic population.

Methods:
Data were collected from 672 patients seen between December of 2014 and February of 2016 in the Department of Auricular Reconstruction at the Plastic Surgery Hospital of Peking Union Medical College. All patients were examined by trained clinicians and classified into one of three grades of microtia. Co-occurring congenital anomalies were detected and recorded.

Results:
The majority of study participants were male patients (72 percent), and most participants had unilateral microtia (93 percent, 68 percent of whom had right-side microtia). Two hundred ninety-three patients (44 percent) had one or more associated anomalies. The most commonly occurring comorbid malformations were those of the ear, face, and neck (40 percent of all associated malformations); musculoskeletal system (35 percent); and cardiovascular system (11 percent).

Conclusions:
These data represent the first detailed and thematic study of microtia and associated congenital anomalies in a Chinese clinical population. Substantial clinical heterogeneity was observed, and the prevalence of comorbid congenital malformations was high. Future studies investigating congenital anomalies associated with microtia are needed to improve understanding of its cause.
68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Militano Vincenzo , Afaq Asim , Bomanji Jamshed 
Published: November 2018

Abstract
This case highlights that liposarcoma shows 68Ga–prostate-specific membrane antigen avidity and should be included in the differential diagnosis of patients with avid muscle lesions to avoid an incorrect diagnosis of metastasis.
Clinical relevance of single nucleotide polymorphisms in the CXCL1 and CXCL12 genes in patients with major trauma
Authors: Wang Xiao , Zhang An-Qiang , Gu Wei , Wen Da-Lin , Lu Hong-Xiang , Yang Jian-Hua , Wang Xu , Deng Jin , Zhang Hong-Qi , Du Ding-Yuan , Zhang Lian-Yang , Zeng Ling , Jiang Jian-Xin 
Published: November 2018

BACKGROUND
Genetic backgrounds have been recognized as significant determinants of susceptibility to sepsis. CXC chemokines play a significant role in innate immunity against infectious diseases. Genetic polymorphisms of CXC chemokine genes have been widely studied in inflammatory and infectious diseases but not in sepsis. Thus, we aimed to investigate the clinical relevance of CXC chemokine gene polymorphisms and susceptibility to sepsis in a traumatically injured population.

METHODS
Thirteen tag single nucleotide polymorphisms were selected from CXC chemokine genes using a multimarker tagging algorithm in the Tagger software. Three independent cohorts of injured patients (n = 1700) were prospectively recruited. Selected single nucleotide polymorphisms were genotyped using an improved multiplex ligation detection reaction method. Cytokine production in lipopolysaccharide-stimulated whole blood was measured using an enzyme-linked immunosorbent assay.

RESULTS
Among the 13 tag single nucleotide polymorphisms, four single nucleotide polymorphisms (rs1429638, rs266087, rs2297630, and rs2839693) were significantly associated with the susceptibility to sepsis, and three (rs3117604, rs1429638, and rs4074) were significantly associated with an increased multiple organ dysfunction score in the derivation cohort. However, only the clinical relevance of rs1429638 and rs266087 was confirmed in the validation cohorts. In addition, rs2297630 was significantly associated with interleukin 6 production.

CONCLUSION
The rs1429638 polymorphism in the CXCL1 gene and the rs2297630 polymorphism in the CXCL12 gene were associated with altered susceptibility to sepsis and might be used as important genetic markers to assess the risks of sepsis in trauma patients.

LEVEL OF EVIDENCE
Prognostic and epidemiologic study, level II.
Does the leaf economic spectrum hold within plant functional types? A Bayesian multivariate trait meta-analysis
Authors: Shiklomanov Alexey N. , Cowdery Elizabeth M. , Bahn Michael , Byun Chaeho , Jansen Steven , Kramer Koen , Minden Vanessa , Niinemets Ülo , Onoda Yusuke , Soudzilovskaia Nadejda A. , Dietze Michael C. 
Published: November 2018

AbstractWe investigated whether global leaf economic relationships are also present within plant functional types (PFTs), and the extent to which this hierarchical structure can be used to constrain trait estimates. We developed a hierarchical multivariate Bayesian model that assumes separate means and covariance structures within and across PFTs and fit this model to seven leaf traits from the TRY database related to leaf morphology, biochemistry, and photosynthetic metabolism. Trait correlations were generally consistent in direction within and across PFTs, and consistent with predictions of the leaf economic spectrum. However, correlation strength varied substantially across PFTs indicating that leaf economic relationships within PFTs are often confounded by the unique physiology of certain plant types or environmental conditions in certain biomes. Leveraging covariance in multivariate models reduced uncertainties in mean trait estimates, particularly for undersampled trait-PFT combinations. However, additional constraint from the across-PFT hierarchy was limited.Data accessibilityThe R code and ancillary data for running these analyses is publicly available online via the Open Science Framework athttps://osf.io/w8y73/. The TRY data request used for this analysis has been archived athttp://try-db.org, and can be retrieved by providing the TRY data request ID (#1584). Alternatively, the exact preformatted data used in this analysis are available on request to Alexey Shiklomanov (alexey.shiklomanov@pnnl.gov).
Characterization of the endocrine pancreas in Type 1 Diabetes: islet size is maintained but islet number is markedly reduced
Authors: Seiron Peter , Wiberg Anna , Krogvold Lars , Jahnsen Frode Lars , Dahl-Jørgensen Knut , Skog Oskar , Korsgren Olle 
Published: November 2018

AbstractInsulin deficiency in type 1 diabetes (T1D) is generally considered a consequence of specific beta-cell loss. Since healthy pancreatic islets consist of ~65% beta cells, this would lead to reduced islet size if the beta cells are not replaced by other cells or tissue. The number of islets per pancreas volume (islet density) would not be affected.In this study, we compared the islet density, size, and size distribution in subjects with recent-onset or long-standing T1D, with that in matched non-diabetic subjects. Results show that subjects with T1D, regardless of disease duration, had a dramatically reduced islet number per mm2, while the islet size was similar in all groups. Insulin-negative islets in T1D subjects were dominated by glucagon-positive cells that frequently had lost the alpha-cell transcription factor ARX while instead expressing PDX1, normally expressed in beta cells.Based on our findings, we propose that failure during childhood to establish a sufficient islet number to reach the beta-cell mass needed to cope with episodes of increased insulin demand contributes to T1D susceptibility. Exhaustion induced by relative lack of beta cells could then potentially drive beta-cell dedifferentiation to alpha-cells, explaining the preserved islet size observed in T1D compared to controls.
Predictive coding of action intentions in dorsal and ventral visual stream is based on visual anticipations, memory-based information and motor preparation
Authors: Monaco Simona , Malfatti Giulia , Zendron Alessandro , Pellencin Elisa , Turella Luca 
Published: November 2018

AbstractPredictions of upcoming movements are based on several types of neural signals that span the visual, somatosensory, motor and cognitive system. Thus far, pre-movement signals have been investigated while participants viewed the object to be acted upon. Here, we studied the contribution of information other than vision to the classification of preparatory signals for action, even in absence of online visual information. We used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA) to test whether the neural signals evoked by visual, memory-based and somato-motor information can be reliably used to predict upcoming actions in areas of the dorsal and ventral visual stream during the preparatory phase preceding the action, while participants were lying still. Nineteen human participants (nine women) performed one of two actions towards an object with their eyes open or closed. Despite the well-known role of ventral stream areas in visual recognition tasks and the specialization of dorsal stream areas in somato-motor processes, we decoded action intention in areas of both streams based on visual, memory-based and somato-motor signals. Interestingly, we could reliably decode action intention in absence of visual information based on neural activity evoked when visual information was available, and vice-versa. Our results show a similar visual, memory and somato-motor representation of action planning in dorsal and ventral visual stream areas that allows predicting action intention across domains, regardless of the availability of visual information.
Additive Dose Response Models: Defining Synergy
Authors: Lederer Simone , Dijkstra Tjeerd M.H. , Heskes Tom 
Published: November 2018

AbstractIn synergy studies, one focuses on compound combinations that promise a synergistic or antagonistic effect. With the help of high-throughput techniques, a huge amount of compound combinations can be screened and filtered for suitable candidates for a more detailed analysis. Those promising candidates are chosen based on the deviance between a measured response and an expected non-interactive response. A non-interactive response is based on a principle of no interaction, such as Loewe Additivity [Loewe, 1928] or Bliss Independence [Bliss, 1939]. In Lederer et al. [2018a], an explicit formulation of the hitherto implicitly defined Loewe Additivity has been introduced, the so-called Explicit Mean Equation. In the current study we show that this Explicit Mean Equation outperforms the original implicit formulation of Loewe Additivity and Bliss Independence when measuring synergy in terms of the deviance between measured and expected response. Further, we show that a deviance based computation of synergy outper-forms a parametric approach. We show this on two datasets of compound combinations that are categorized into synergistic, non-interactive and antagonistic [Yadav et al., 2015, Cokol et al., 2011].
A system biology approach reveals cellular pathway differences between follicular thyroid carcinoma and follicular thyroid adenoma
Authors: Hossain Md. Ali , Asa Tania Akter , Rahman Md. Mijanur , Quinn Julian M.W. , Huq Fazlul , Moni Mohammad Ali 
Published: November 2018

AbstractPathogenic mechanisms that underlie malignant follicular thyroid carcinoma (FTC) development are poorly understood. To identify key genes and pathways driving malignant behaviour we employed a system biology-based integrative analyses comparing FTC transcriptomes with a similar but benign lesion, follicular thyroid adenoma (FTA). We identified differentially expressed genes (DEGs) in microarray gene expression datasets (n=52) of FTCs and FTA tissues. Pathway analyses of DEGs using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) resources revealed significant pathways, and pathway hub genes using protein-protein interactions (PPI). We identified 598 DEGs (relative to FTAs) in FTCs and 12 significant pathways with altered expression in FTC. 10 GO groups were significantly connected with FTC-high expression DEGs and 80 with low-FTC expression. PPI analysis identified 12 potential hub genes based on degree and betweenness centrality. Moreover, 10 transcription factors (TFs) were identified that may underlie DEG expression as well as a number of microRNA (miRNAs). Thus, we identified DEGs, pathways, TFs and miRNAs that reflect molecular mechanisms differing between FTC and benign FTA. These may constitute biomarkers that distinguish these lesions and, given the similarities and common origin of the lesions, they may also be indicators of malignant progression potential.
The influence of rare variants in circulating metabolic biomarkers
Authors: Riveros-Mckay Fernando , Oliver-Williams Clare , Karthikeyan Savita , Walter Klaudia , Kundu Kousik , Ouwehand Willem H , Roberts David , Angelantonio Emanuele Di , Soranzo Nicole , Danesh John , Wheeler Eleanor , Zeggini Eleftheria , Butterworth Adam S , Barroso Inês 
Published: November 2018

AbstractCirculating metabolite levels are biomarkers for cardiovascular disease (CVD). We tested association between rare sequence variants and 226 serum lipoproteins, lipids and amino acids in 7,142 healthy participants. Gene-based association analyses identified novel gene-trait associations with ACSL1, MYCN, FBXO36 and B4GALNT3 (p<2.5 × 10−6), and confirmed established associations. Regulation of the pyruvate dehydrogenase (PDH) complex was associated for the first time, in gene set analyses, with IDL and LDL parameters, as well as circulating cholesterol (pMETASKAT <2.41 × 10−6). Individuals at the lower tails of the distributions of four out of 49 lipoproteins and lipids had an excess of predicted deleterious variants in lipoprotein disorder and metabolism gene sets (ppermutation<0.00037). These four traits were CVD risk factors (e.g. S-VLDL-C), demonstrating that rare “protective” variation is a significant contributor to lipoprotein levels in a healthy population. In conclusion, rare variant analysis of these important metabolic biomarkers reveals novel loci and pathways involved in their regulation.
Repression of an activity-dependent autocrine insulin signal is required for sensory neuron development inC. elegans
Authors: Horowitz Lauren Bayer , Brandt Julia P. , Ringstad Niels 
Published: November 2018

AbstractNervous system development is instructed both by genetic programs and activity-dependent refinement of gene expression and connectivity. How these mechanisms are integrated remains poorly understood. Here, we report that the regulated release of insulin-like peptides (ILPs) during development of theC. elegansnervous system accomplishes such an integration. We find that the p38 MAP kinase PMK-3, which is required for the differentiation of chemosensory BAG neurons, functions by limiting expression of an autocrine ILP signal that represses a chemosensory-neuron fate. ILPs are released from BAGs in an activity-dependent manner during embryonic development, and regulate neurodifferentiation through a non-canonical insulin receptor signaling pathway. The differentiation of a specialized neuron-type is, therefore, coordinately regulated by a genetic program that controls ILP expression and by neural activity, which regulates ILP release. Autocrine signals of this kind may have general and conserved functions as integrators of deterministic genetic programs with activity-dependent mechanisms during neurodevelopment.
Brain network dynamics during spontaneous strategy shifts and incremental task optimization
Authors: Allegra Michele , Seyed-Allaei Shima , Schuck Nicolas W. , Amati Daniele , Laio Alessandro , Reverberi Carlo 
Published: November 2018

AbstractWith practice, humans may improve their performance in a task by either optimizing a known strategy or discovering a novel, potentially more fruitful strategy. How does the brain support these two fundamental abilities? In the present experiment, subjects performed a simple perceptual decision-making task. They could either use and progressively optimize an instructed strategy based on stimulus position, or spontaneously devise and then use a new strategy based on stimulus color. We investigated how local and long-range BOLD coherence behave during these two types of strategy learning by applying a recently developed unsupervised fMRI analysis technique that was specifically designed to probe the presence of transient correlations. Converging evidence showed that the posterior portion of the default network, i.e. the precuneus and the angular gyrus bilaterally, has a central role in the optimization of the current strategy: these regions encoded the relevant spatial information, increased the level of local coherence and the strength of connectivity with other relevant regions in the brain (e.g. visual cortex, dorsal attention network). This increase was proportional to the task optimization achieved by subjects, as measured by the reduction of reaction times, and was transiently disrupted when subjects were forced to change strategy. By contrast, the anterior portion of the default network (i.e. medial prefrontal cortex) together with rostral portion of the fronto-parietal network showed an increase in local coherence and connectivity only in subjects that would at some point spontaneously choose the new strategy. Overall, our findings shed light on the dynamic interactions between regions related with attention and with cognitive control, underlying the balance between strategy exploration and exploitation. Results suggest that the default network, far from being “shut-down” during task performance, has a pivotal role in the background exploration and monitoring of potential alternative courses of action.
GSK3β-SCFFBXW7mediated phosphorylation and ubiquitination of IRF1 are required for its transcription-dependent turnover
Authors: Garvin Alexander J. , Khalaf Ahmed H.A. , Rettino Alessandro , Xicluna Jerome , Butler Laura , Morris Joanna R. , Heery David M. , Clarke Nicole M. 
Published: November 2018

ABSTRACTIRF1 (Interferon Regulatory Factor-1) is the prototype of the IRF family of DNA binding transcription factors. IRF1 protein expression is regulated by transient up-regulation in response to external stimuli followed by rapid degradation via the ubiquitin-proteasome system. Here we report that DNA bound IRF1 turnover is promoted by GSK3β (Glycogen Synthase Kinase 3β) via phosphorylation of the T181 residue which generates a phosphodegron for the SCF (Skp-Cul-Fbox) ubiquitin E3-ligase receptor protein Fbxw7α (F-box/WD40 7). This regulated turnover is essential for IRF1 activity, as mutation of T181 results in an improperly stabilised protein that accumulates at target promoters but fails to induce RNA-Pol-II elongation and subsequent transcription of target genes. Consequently, the anti-proliferative activity of IRF1 is lost in cell lines expressing T181A mutant. Further, cell lines with dysfunctional Fbxw7 are less sensitive to IRF1 overexpression, suggesting an important co-activator function for this ligase complex. As T181 phosphorylation requires both DNA binding and RNA-Pol-II elongation, we propose that this event acts to clear “spent” molecules of IRF1 from transcriptionally engaged target promoters.
Unexpected Loss of Sensitivity to the nAChR Antagonist Activity of Mecamylamine and DHβE in Nicotine-Tolerant C57BL/6J Mice
Authors: Moura Fernando B. de , McMahon Lance R. 
Published: November 2018

AbstractThere has always been interest in developing nAChR antagonists as smoking cessation aids, to add to nAChR agonists (e.g., nicotine replacement) already used for that indication. Previous studies have demonstrated that daily nicotine treatment confers tolerance to some of the effects of nicotine, as well as cross-tolerance to other nAChR agonists. The current study assessed the extent to which antagonism of nicotine varies as a function of daily nicotine treatment. The rate-decreasing and hypothermic effects of nicotine, as well as antagonism of those effects, were examined in C57BL/6J mice before, during treatment with, and after discontinuation of three daily injections of 1.78 mg/kg nicotine. The nonselective nAChR antagonist mecamylamine and the β2 nAChR antagonist DHβE were studied in combination with nicotine. The ED50values of nicotine to produce rate-decreasing and hypothermic effects were, respectively, 0.44 and 0.82 mg/kg prior, 1.6 and 3.2 mg/kg during, and 0.74 and 1.1 mg/kg after discontinuation of daily nicotine treatment. Prior to daily nicotine treatment, mecamylamine decreased response rate and rectal temperature; however, during daily nicotine, mecamylamine (up to 5.6 mg/kg) only decreased rectal temperature. DHβE (up to 5.6 mg/kg) when studied prior to daily nicotine decreased rectal temperature, but that decrease was abolished during chronic nicotine treatment. Mecamylamine and DHβE antagonized the rate-decreasing and hypothermic effects of nicotine before and after daily nicotine; however, during daily nicotine, mecamylamine and DHβE antagonized only the hypothermic effects of nicotine. The differential antagonism of rate-decreasing and hypothermic effects implicates differential involvement of nAChR subtypes. The decreased capacity of mecamylamine and DHβE to antagonize nicotine during chronic nicotine treatment may indicate that their effectiveness as smoking cessations might vary as a function of nicotine tolerance and dependence.