bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity Within an Extraperitoneal Ureteral Herniation Detected on Bone Scan, Associated With a Partially Duplicated Collecting System
Authors: Robbins Robert , Bhat Roopa , Baqar Mohamed , Singh Amolak 
Published: November 2020

Abstract
A 64-year-old man with history of renal stones and prostate cancer presented for evaluation of osseous metastatic disease due to elevated prostate-specific antigen (13.7 ng/mL). A 99mTc-labeled bone scan demonstrated unusual linear uptake projecting over the lower pelvis extending into the scrotum. Follow-up CT confirmed a rare case of inguinoscrotal extraperitoneal herniation of the ureter associated with a partially duplicated left renal collecting system. The left-sided inguinoscrotal uptake was within the herniated ureter, potentially mimicking disease within the pelvis.
Extensive Postchemotherapy Calcinosis Cutis in a Non-Hodgkin Lymphoma Patient With Spontaneous Resolution
Authors: Mishra Vineet , Madurai Kalimuthu Lokeshwaran , Singh Prakash , Ora Manish , Gambhir Sanjay 
Published: November 2020

Abstract
We report the case of a 30-year-old woman with stage IV, non-Hodgkin lymphoma. Baseline 18F-FDG PET/CT scan revealed lymphadenopathy with breasts and skeletal involvement. She received 3 cycles of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) chemotherapy without significant adverse effects. Biochemical examinations before and after chemotherapies were unremarkable. Interim18F-FDG PET/CT showed a partial treatment response. However, there was an appearance of FDG-avid coarse calcification in breasts. Cutaneous and subcutaneous regions of elbows, pelvis, and thighs showed similar calcifications. Posttherapy PET/CT showed a significant resolution of calcinosis cutis. This case presents a postchemotherapy idiopathic calcinosis cutis with rapid spontaneous resolution.
A New Type of Three-Dimensional Customized Composite Implant in Reconstruction of Large Skull Defects
Authors: Huang Qinghua , Yang Bin , Li Binghang , Ma Hengyuan 
Published: November 2020

Abstract
Large skull defects can result in chronic injury to intracranial tissues as well as psychological trauma for patients, and their repair presents a challenge to surgeons. Hydroxyapatite has been used in reconstructing skull defects for many years, but it is difficult to adjust the shape and size of the material intraoperatively, especially for large defects. With three-dimensional digital technology, a new type of customized composite implant made of epoxide acrylate maleic and hydroxyapatite has been applied in clinical practice. In this retrospective review, 15 patients with large skull defects (4 female and 11 male, at a mean age of 36.4 years, range from 24–65 years) were treated with the novel customized composite implant, reconstructing the large skull defects successfully. During the average 2.2 years follow-up period (range 0.5–4 years), complications including infection, cerebrospinal fluid leakage, intracranial hemorrhage, or implant exposurea were not occured, only 1 patient (6.7%) with a seroma managed non-operatively. The customized implants, which required no intraoperative adjustments and are about a third of the cost of titanium implants, are an excellent alternative for large skull defect repair.
TNMplot.com: a web tool for the comparison of gene expression in normal, tumor and metastatic tissues
Authors: Bartha Áron , Győrffy Balázs 
Published: November 2020

ABSTRACTGenes showing higher expression in either tumor or metastatic tissues can help in better understanding tumor formation, and can serve as biomarkers of progression or as therapy targets with minimal off-target effects. Our goal was to establish an integrated database using available transcriptome-level datasets and to create a web-platform enabling mining of this database by comparing normal, tumor and metastatic data across all genes in real time.We utilized data generated by either gene arrays or RNA-seq. Gene array data were manually selected from NCBI-GEO. RNA sequencing data was downloaded from the TCGA, TARGET, and GTEx repositories. TCGA and TARGET contain predominantly tumor and metastatic samples from adult and pediatric patients, while GTEx samples are from healthy tissues. Statistical significance was computed using Mann-Whitney or Kruskall-Wallis tests.The entire database contains 56,938 samples including 33,520 samples from 3,180 gene chip-based studies (453 metastatic, 29,376 tumorous and 3,691 normal samples), 11,010 samples from TCGA (394 metastatic, 9,886 tumorous and 730 normal), 1,193 samples from TARGET (1 metastatic, 1,180 tumor, 12 normal) and 11,215 normal samples from GTEx. The most consistently up-regulated genes across multiple tumor types were TOP2A (mean FC=7.8), SPP1 (FC=7.0) and CENPA (FC=6.03) and the most consistently down-regulated gene was ADH1B (mean FC=0.15). Validation of differential expression using equally sized training and test sets confirmed reliability of the database in breast, colon, and lung cancer (p<0.0001). The online analysis platform enables unrestricted mining of the database and is accessible atwww.tnmplot.com.
driveR: A Novel Method for Prioritizing Cancer Driver Genes Using Somatic Genomics Data
Authors: Ülgen Ege , Sezerman O. Uğur 
Published: November 2020

AbstractCancer develops due to “driver” alterations. Numerous approaches exist for predicting cancer drivers from cohort-scale genomic data. However, methods for personalized analysis of driver genes are underdeveloped.In this study, we developed a novel personalized/batch analysis approach for driver gene prioritization utilizing somatic genomic data, called driveR. Combining genomic information and prior biological knowledge, driveR accurately prioritizes cancer driver genes via a multi-task learning model.Testing on 28 different datasets, this study demonstrates that driveR performs adequately, outperforms existing approaches, and is an accurate and easy-to-utilize approach for prioritizing driver genes in cancer genomes. driveR is available on CRAN:https://cran.r-project.org/package=driveR.
Epigenome-Wide Study of Brain DNA Methylation Among Opioid Users and Controls
Authors: Shu Chang , Sosnowski David W. , Tao Ran , Deep-Soboslay Amy , Kleinman Joel E. , Hyde Thomas M. , Jaffe Andrew E. , Sabunciyan Sarven , Maher Brion S. 
Published: November 2020

AbstractOpioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. To clarify the association between opioid abuse and DNA methylation, we conducted an epigenome-wide analysis (EWAS) of DNA methylation in brains of individuals who died from opioid intoxication and controls. Tissue samples were extracted from the dorsolateral prefrontal cortex of 160 deceased individuals (Mage= 35.15,SD= 9.42 years; 62% male; 78% White). The samples included 73 individuals who died of opioid intoxication, 59 group-matched psychiatric controls, and 28 group-matched normal controls. EWAS was implemented using the Illumina Infinium MethylationEPIC BeadChip; analyses adjusted for sociodemographic characteristics, negative control and ancestry principal components, cellular composition, and surrogate variables. Epigenetic age was calculated using the Horvath and Levine clocks, and gene ontology (GO) analyses were performed. No CpG sites were epigenome-wide significant after multiple testing correction, but 13 sites reached nominal significance (p < 1.0 x 10-5). There was a significant association between opioid use and Levine phenotypic age (b= 2.24,se= 1.11,p= .045). Opioid users were approximately two years phenotypically older compared to controls. GO analyses revealed enriched pathways related to cell function and neuron differentiation, but no terms survived multiple testing correction. Results inform our understanding of the neurobiology of opioid use, and future research with larger samples across stages of opioid use will elucidate the complex genomics of opioid abuse.
CoaTran: Coalescent tree simulation along a transmission network
Authors: Moshiri Niema 
Published: November 2020

AbstractMotivationThe ability to simulate coalescent viral phylogenies constrained by a given transmission network can enable the benchmarking of computational tools used in molecular epidemiology as well as the ability to gain insights into unobservable aspects of the virology of a novel pathogen. However, such simulation experiments require generating a large number of technical simulation replicates, and existing tools for coalescent simulations along a transmission network are too slow to conduct such experiments at the scale of the global population.ResultsCoaTran is a massively scalable tool that simulates a coalescent viral phylogeny constrained by a user-provided transmission network. CoaTran is written in highly-optimized C++ code and can generate global population scale phylogenetic coalescent simulations in seconds to minutes.AvailabilityCoaTran is freely available athttps://github.com/niemasd/CoaTranas an open-source software project.Contactniema@ucsd.eduSupplementary informationSupplementary data are available online.
Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma
Authors: Prummel Karin D. , Crowell Helena L. , Nieuwenhuize Susan , Brombacher Eline C. , Daetwyler Stephan , Soneson Charlotte , Kresoja-Rakic Jelena , Ronner Manuel , Kocere Agnese , Ernst Alexander , Labbaf Zahra , Clouthier David E. , Firulli Anthony B. , Sánchez-Iranzo Héctor , Naganathan Sundar R. , O’Rourke Rebecca , Raz Erez , Mercader Nadia , Burger Alexa , Felley-Bosco Emanuela , Huisken Jan , Robinson Mark D. , Mosimann Christian 
Published: November 2020

AbstractThe mesothelium forms epithelial membranes that line the bodies cavities and surround the internal organs. Mesothelia widely contribute to organ homeostasis and regeneration, and their dysregulation can result in congenital anomalies of the viscera, ventral wall defects, and mesothelioma tumors. Nonetheless, the embryonic ontogeny and developmental regulation of mesothelium formation has remained uncharted. Here, we combine genetic lineage tracing,in totolive imaging, and single-cell transcriptomics in zebrafish to track mesothelial progenitor origins from the lateral plate mesoderm (LPM). Our single-cell analysis uncovers a post-gastrulation gene expression signature centered onhand2that delineates distinct progenitor populations within the forming LPM. Combining gene expression analysis and imaging of transgenic reporter zebrafish embryos, we chart the origin of mesothelial progenitors to the lateral-most,hand2-expressing LPM and confirm evolutionary conservation in mouse. Our time-lapse imaging of transgenichand2reporter embryos captures zebrafish mesothelium formation, documenting the coordinated cell movements that form pericardium and visceral and parietal peritoneum. We establish that the primordial germ cells migrate associated with the forming mesothelium as ventral migration boundary. Functionally,hand2mutants fail to close the ventral mesothelium due to perturbed migration of mesothelium progenitors. Analyzing mouse and human mesothelioma tumors hypothesized to emerge from transformed mesothelium, we findde novoexpression of LPM-associated transcription factors, and in particular of Hand2, indicating the re-initiation of a developmental transcriptional program in mesothelioma. Taken together, our work outlines a genetic and developmental signature of mesothelial origins centered around Hand2, contributing to our understanding of mesothelial pathologies and mesothelioma.
Exposure to Airborne Bacteria Depends upon Vertical Stratification and Vegetation Complexity
Authors: Robinson Jake M. , Cando-Dumancela Christian , Antwis Rachael E. , Cameron Ross , Liddicoat Craig , Poudel Ravin , Weinstein Philip , Breed Martin F. 
Published: November 2020

AbstractExposure to biodiverse aerobiomes may support human health, but it is unclear which ecological factors influence exposure. Few studies have investigated near-surface green space aerobiome dynamics, and no studies have investigated aerobiome vertical stratification in different green spaces. We used columnar sampling and next generation sequencing of the bacterial 16S rRNA gene, combined with geospatial and network analyses to investigate aerobiome spatio-compositional dynamics. We show a strong effect of habitat on bacterial diversity and network complexity. We observed aerobiome vertical stratification and network complexity that was contingent on habitat type. Tree density, closer proximity, and canopy coverage associated with greater aerobiome alpha diversity. Grassland aerobiomes exhibited greater proportions of putative pathogens compared to scrub, and also stratified vertically. We provide new insights into the urban ecosystem with potential importance for public health, whereby the possibility of differential aerobiome exposures appears to depend on habitat type and height in the airspace.
Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics
Authors: Gordillo-Marañón María , Zwierzyna Magdalena , Charoen Pimphen , Drenos Fotios , Chopade Sandesh , Shah Tina , Engmann Jorgen , Casas Juan-Pablo , Chaturvedi Nishi , Papacosta Olia , Wannamethee Goya , Wong Andrew , Sofat Reecha , Kivimaki Mika , Price Jackie F , Hughes Alun D , Gaunt Tom R , Lawlor Deborah A , Gaulton Anna , Hingorani Aroon D , Schmidt Amand F , Finan Chris 
Published: November 2020

AbstractDrug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter its expression or function, as a tool to anticipate the effect of drug action on the same target. Here, we applied MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets were further prioritized using genetic co-localization, protein expression profiles from the Human Protein Atlas and, for targets with a licensed drug or an agent in clinical development, by sourcing data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with circulating blood lipids (HDL-C, LDL-C and triglycerides), we were able to robustly prioritize 30 targets that might elicit beneficial treatment effects in the prevention or treatment of CHD. The prioritized list included NPC1L1 and PCSK9, the targets of licensed drugs whose efficacy has been already proven in clinical trials. To conclude, we discuss how this approach can be generalized to other targets, disease biomarkers and clinical end-points to help prioritize and validate targets during the drug development process.One Sentence SummaryWe provide genetic support for lipid-modifying drug targets for coronary heart disease prevention using drug target Mendelian randomization and further prioritization based on clinical and biological evidence.
Nonrandom spatial distribution of Neotropic Cormorants (Phalacrocorax brasilianus) along a coastal highway in Lima, Peru
Authors: Lozano-Sanllehi Sebastián , Zavalaga Carlos B. 
Published: November 2020

AbstractNeotropic Cormorants (Phalacrocorax brasilianus) are common seabirds along the Peruvian coast. They frequently perch on trees, poles and port structures in urban areas, causing discomfort and esthetic problems due to the dropping of their feces on infrastructure and people. Hundreds of these birds rest on lighting poles and telephone cables along a 12.7 km highway in the coastal strip of the city of Lima, Peru. We hypothesized that the distribution of the cormorants along this highway is clustered and could be associated with physical features of both the coast and the adjacent marine area. Half-monthly or monthly surveys were performed from July 2018 to March 2020 in the Circuito de Playas de la Costa Verde highway. At each survey, cormorants were counted per lighting pole and adjacent telephone cables (pole-cable) at four count hours (0600 h, 1000 h, 1400 h and 1800 h). Our results revealed that daily bird numbers varied from 46 to 457 individuals and that only 17% of the total number of pole-cables (N = 651) was occupied once by at least one individual. The number of cormorants also varied between count hours within the same day (higher numbers at 1000 h and 1400 h). Birds were clustered into a maximum of five hotspots along the highway. According to the Akaike’s information-theoretic approach applied to Poisson GLMM, higher numbers of cormorants on pole-cables were associated mainly to a closer distance from these structures to the shoreline and to the surf zone, suggesting that Neotropic Cormorants may select such pole-cables as optimal sites for sighting and receiving clues of prey availability. Based on the results, the use of nonlethal deterrents and the relocation of these birds to other perching structures on nearby groynes could be the most suitable and eco-friendly solution for the problems caused by their droppings.
Default Mode Network Ventral Hub Connectivity Associated with Memory Impairment in Temporal Lobe Epilepsy Surgery
Authors: Neal Elliot G. , Di Long , Park You Jeong , Finch Austin , Korneli Ferdinand , Maciver Stephanie , Bezchlibnyk Yarema B. , Schoenberg Mike R. , Vale Fernando L. 
Published: November 2020

AbstractIn patients undergoing surgery for intractable temporal lobe epilepsy, the relationship between the default mode network and patients’ neurocognitive outcome remains unclear. The objective of this study is to employ non-invasive network mapping to identify the relationship between subdivisions of the default mode network and neurocognitive function before and after epilepsy surgery in patients with temporal lobe epilepsy.Twenty-seven medically patients with medically refractory temporal lobe epilepsy were prospectively enrolled and received resting state functional MRI and neuropsychological testing both pre- and post-operatively. Connectivity within the default mode network was modeled and average connectivity within the networks was calculated.Higher pre-operative connectivity in the ventral default mode network hub correlated with impaired baseline performance in a visual memory task. Post-operatively, a decrease in ventral but not dorsal default mode network connectivity was correlated with a deterioration of verbal and logical memory after surgery.Overall, higher connectivity in the ventral default mode network hub was associated with poor memory function in patients with temporal lobe epilepsy both before and after temporal lobe surgery. Pre-operatively, higher ventral connectivity was associated with worse visual function. Post-operatively, decreased connectivity of the ventral and dorsal default mode network was correlated with a greater decrease in logical and verbal memory when compared with the pre-operation baseline. An imbalance in default mode network connectivity towards the ventral stream and more widespread epilepsy networks may be used to predict memory impairments following surgical intervention and may lead to more tailored surgical decision making based on this non-invasive network modeling.
Detection and functional resolution of soluble multimeric immune complexes by a comprehensive FcγR reporter cell panel
Authors: Chen Haizhang , Maul-Pavicic Andrea , Holzer Martin , Huber Magdalena , Salzer Ulrich , Chevalier Nina , Voll Reinhard E. , Hengel Hartmut , Kolb Philipp 
Published: November 2020

AbstractFc-gamma receptor (FcγR) activation by soluble IgG immune complexes (sICs) represents a major mechanism of inflammation in certain autoimmune diseases such as systemic lupus erythematosus (SLE). A robust and scalable test system allowing for the detection and quantification of sIC bioactivity is missing. Previously described FcγR interaction assays are limited to certain FcγRs, lack scalability and flexibility, are not indicative of receptor activation or lack sensitivity towards sIC size. We developed a comprehensive reporter cell panel detecting individual activation of FcγRs from humans and the mouse. The reporter cell lines were integrated into an assay format that provides flexible read-outs enabling the quantification of sIC reactivity via ELISA or a fast detection using flow cytometry. This identified FcγRIIA(H) and FcγRIIIA as the most sIC-sensitive FcγRs in our test system. Applying the assay we demonstrate that sICs versus immobilized ICs are fundamentally different FcγR-ligands with regard to FcγR preference and signal strength. Reaching a detection limit in the very low nanomolar range, the assay proved also to be sensitive to sIC stoichiometry and size enabling for the first time a complete reproduction of the Heidelberger-Kendall precipitation curve in terms of immune receptor activation. Analyzing sera from SLE patients and mouse models of lupus and arthritis proved that sIC-dependent FcγR activation has predictive capabilities regarding severity of SLE disease. The new methodology provides a sensitive, scalable and comprehensive tool to evaluate the size, amount and bioactivity of sICs in all settings.One Sentence SummaryIn this study we established a comprehensive FcγR reporter cell assay enabling the detection and quantification of soluble immune complexes generated in experimental and clinical settings.
Mechanistic Dissection of Spatial Organization in NF-κB Signaling Pathways by Hybrid Simulations
Authors: Wu Yinghao , Dhusia Kalyani , Su Zhaoqian 
Published: November 2020

ABSTRACTThe nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is one of the most important transcription factors involved in the regulation of inflammatory signaling pathways. Inappropriate activation of these pathways has been linked to autoimmunity and cancers. Emerging experimental evidences have been showing the existence of elaborate spatial organizations for various molecular components in the pathways. One example is the scaffold protein tumor necrosis factor receptor associated factor (TRAF). While most TRAF proteins form trimeric quaternary structure through their coiled-coil regions, the N-terminal region of some members in the family can further be dimerized. This dimerization of TRAF trimers can drive them into higher-order clusters as a response to receptor stimulation, which functions as a spatial platform to mediate the downstream poly-ubiquitination. However, the molecular mechanism underlying the TRAF protein clustering and its functional impacts are not well-understood. In this article, we developed a hybrid simulation method to tackle this problem. The assembly of TRAF-based signaling platform at the membrane-proximal region is modeled with spatial resolution, while the dynamics of downstream signaling network, including the negative feedbacks through various signaling inhibitors, is simulated as stochastic chemical reactions. These two algorithms are further synchronized under a multiscale simulation framework. Using this computational model, we illustrated that the formation of TRAF signaling platform can trigger an oscillatory NF-κB response. We further demonstrated that the temporal patterns of downstream signal oscillations are closely regulated by the spatial factors of TRAF clustering, such as the geometry and energy of dimerization between TRAF trimers. In general, our study sheds light on the basic mechanism of NF-κB signaling pathway and highlights the functional importance of spatial regulation within the pathway. The simulation framework also showcases its potential of application to other signaling pathways in cells.