bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Infliximab Biosimilar Versus Originator in a Pediatric United Kingdom Inflammatory Bowel Disease Induction Cohort
Authors: Chanchlani Neil , Mortier Kajal , Williams Linda J. , Muhammed Rafeeq , Auth Marcus K.H. , Cosgrove Mike , Fagbemi Andrew , Fell John , Chong Sonny , Zamvar Veena , Hyer Warren , Bisset W. Michael , Morris Mary‐Anne , Rodrigues Astor , Mitton Sally G. , Bunn Su , Beattie R. Mark , Willmott Anne , Wilson David C. , Russell Richard K. 
Published: April 2018

ABSTRACTObjectives:The aim of the study was to summarize short‐term effectiveness, safety, and cost of using infliximab biosimilar (IFX‐B) drugs, (Inflectra [Hospira] and Remsima [NAAP]) compared to originator infliximab (IFX‐O) (Remicade [MSD]) in biologic naive pediatric inflammatory bowel disease in the United Kingdom.Methods:Prospective audit of patients starting anti‐tumour necrosis factor (TNF) therapy. Disease severity, response to treatment, and remission rate was measured by Pediatric Crohn's Disease Activity Index (PCDAI) and/or Physician Global Assessment.Results:Between March 2015 and February 2016, 278 patients (175 IFX‐O, 82 IFX‐B, and 21 Adalimumab) were started on anti‐TNF therapy. This was compared with collected data on 398 patients started on IFX‐O from 2011 to 2015. At initiation, median PCDAI was 36 (20,48) (n = 42) in the IFX‐O group and 28 (20,40) (n = 29) in the IFX‐B group, (P = 0.08). Immunosuppression rates were similar: 150/175 (86%) for IFX‐O and 65/82 (79%) for IFX‐B (P > 0.05). Post induction, median PCDAI score was 5 (0,11) (n = 19) and 0 (0,8) (n = 15) in the IFX‐O and IFX‐B groups, respectively (P = 0.35). There was no difference in response to treatment using Physician Global Assessment 85% (n = 28) in IFX‐O group and 86% (n = 19) in IFX‐B group (P > 0.05). Adverse events at initiation and post induction were not different between both groups (P > 0.05). Using conservative calculations, £875,000 would have been saved for a 1‐year period with universal adoption of biosimilars in patients who were instead treated with IFX‐O.Conclusions:IFX‐B is likely as effective as IFX‐O in treating IBD in comparable pediatric populations. Sites should adopt infliximab biosimilar for new starts due to cost reduction with no difference in other parameters.
Cold Panniculitis After Ice Therapy for Supraventricular Tachycardia
Authors: Malia Laurie , Wang Alicia , Scheiner Laurie , Laurich V. Matt 
Published: April 2018

Abstract
A late preterm infant presenting with supraventricular tachycardia (SVT) was admitted to the pediatric intensive care unit because of poor systolic function seen on echocardiogram. The hospitalization was complicated by multiple breakthrough episodes of SVT requiring ice placed on the face during each repeat episode. The infant was later diagnosed as having cold panniculitis secondary to the application of ice to the face on multiple occasions. In children who are hemodynamically stable during SVT episodes, ice is used as first-line treatment. It is important to be aware of how often ice is being applied to the face and the duration of time to limit complications such as cold panniculitis.
Simultaneous Blood Glucose Monitoring During Gastric-Emptying Scintigraphy May Identify Unsuspected Abnormalities
Authors: McWhorter Nathan E. , Abazid Leen , Gorzell Brandon C. , Lynch Jane L. , Salman Umber A. , Metter Darlene F. , Phillips William T. 
Published: April 2018

Purpose
A retrospective study of 197 patients was performed to evaluate utility of simultaneous fingerstick glucose monitoring during standardized solid meal gastric-emptying scintigraphy (GES). We hypothesized the unlabeled carbohydrate components of the standardized meal often empty at different rates than the labeled egg protein component and that simultaneous glucose monitoring may identify rapid carbohydrate gastric emptying.

Methods
Patients were classified as normal, rapid, or delayed gastric emptying from the standardized solid egg meal GES criteria. Further subcategorization was made based on postprandial glycemic excursions above baseline at 30/60 minutes and was delineated as elevated (>75 mg/>85 mg/dL), normal, or diminished (<30 mg/dL) glucose excursion.

Results
Of the 197 patients, solid gastric-emptying rates for 105 were normal, delayed in 54, and rapid in 25 patients, and 13 patients had initially delayed emptying 1 or 2 hours with normal emptying by 4 hours. Of the 105 patients with normal gastric emptying, 58 had elevated, 47 normal, and none had diminished glucose excursions. Of the 54 patients with delayed gastric emptying, 26 had elevated, 16 had normal, and 12 had diminished glucose excursions. Nine patients with normal or delayed gastric emptying but elevated glycemic excursions returned for a liquid glucose GES. In contrast to their standardized GES results, all 9 had rapid emptying with elevated glycemic excursions.

Conclusions
Simultaneous blood glucose monitoring with standardized GES protocols may provide a marker for contradictory findings of rapid gastric emptying of the unlabeled carbohydrate component in the standardized meal and may contribute to unexplained postprandial gastrointestinal symptoms. The additional insights provided by fingerstick glucose monitoring are inexpensive, easy to perform and may provide for new approaches to management of patient's gastrointestinal symptoms.
A Case of Mesh Erosion to the Sigmoid After Laparoscopic Sacrocolpopexy and a Literature Review of Mesh Related Complications
Authors: Lin Xiaoting , Du Pei , Chen Liquan , Gan Yaping , Zhang Xiaowei 
Published: April 2018

Abstract
Sacrocolpopexy has long been the preferred surgical procedure for the management of apical vaginal prolapse. The published literature regarding rectal mesh erosion after sacrocolpopexy includes only 6 cases in MEDLINE. We report a case of sigmoid vaginal fistula identified 4 years after laparoscopic sacrocolpopexy, along with an analysis of the follow-up of 140 patients over 12 months or more.
Liver Transplantation Without Venovenous Bypass: Does Surgical Approach Matter?
Authors: Barbas Andrew S. , Levy Jordan , Mulvihill Michael S. , Goldaracena Nicolas , Dib Martin J. , Al-Adra David P. , Cattral Mark S. , Ghanekar Anand , Greig Paul D. , Grant David R. , Sapisochin Gonzalo , Selzner Markus , McCluskey Stuart A. , McGilvray Ian D. 
Published: April 2018

Background
The use of venovenous bypass in liver transplantation has declined over time. Few studies have examined the impact of surgical approach in cases performed exclusively without venovenous bypass. We hypothesized that advances in liver transplant anesthesia and perioperative care have minimized the importance of surgical approach in the modern era.

Methods
Deceased donor liver transplants at the University of Toronto from 2000 to 2015 were reviewed, all performed without venovenous bypass. First, an unadjusted analysis was performed comparing perioperative outcomes and graft/patient survival for 3 different liver transplant techniques (caval interposition, piggyback, side-to-side cavo-cavostomy). Second, a propensity-matched analysis was performed comparing caval interposition to caval-preserving techniques.

Results
One thousand two hundred thirty-three liver transplants were included in the study. On unadjusted analysis, blood loss, transfusion requirement, postoperative complications, and graft/patient survival were equivalent for the 3 different techniques. To account for possible confounding patient variables, propensity matching was performed. Analysis of the propensity-matched cohorts also demonstrated similar outcomes for caval interposition versus caval-preserving approaches.

Conclusions
In the modern era at centers with a multidisciplinary team, the importance of specific liver transplant technique is minimized. Full or partial cross-clamping of the inferior vena cava is feasible without the use of venovenous bypass.
Database-integrated genome screening (DIGS): exploring genomes heuristically using sequence similarity search tools and a relational database
Authors: Zhu Henan , Dennis Tristan , Hughes Joseph , Gifford Robert J. 
Published: April 2018

ABSTRACTA significant fraction of most genomes is comprised of DNA sequences that have been incompletely investigated. This genomic ‘dark matter’ contains a wealth of useful biological information that can be recovered by systematically screening genomes in silico using sequence similarity search tools. Specialized computational tools are required to implement these screens efficiently. Here, we describe the database-integrated genome-screening (DIGS) tool: a computational framework for performing these investigations. To demonstrate, we screen mammalian genomes for endogenous viral elements (EVEs) derived from the Filoviridae, Parvoviridae, Circoviridae and Bornaviridae families, identifying numerous novel elements in addition to those that have been described previously. The DIGS tool provides a simple, robust framework for implementing a broad range of heuristic, sequence analysis-based explorations of genomic diversity.Availabilityhttp://giffordlabcvr.github.io/DIGS-tool/Contactrobert.gifford@glasgow.ac.ukSupplementary informationSupplementary data are available at Bioinformatics online.
Comment on “Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania”
Authors: Schnorr Stephanie L. , Candela Marco , Rampelli Simone , Turroni Silvia , Henry Amanda G. , Crittenden Alyssa N. 
Published: April 2018

AbstractIn a recent paper, Smits et al. (Science, 25 August 2017, p. 802) report on seasonal changes in the gut microbiome of Hadza hunter-gatherers. They argue that seasonal volatility of some bacterial taxa corresponds to seasonal dietary changes. We address the authors’ insufficient reporting of relevant data and problematic areas in their assumptions about Hadza diet that yield inconsistencies in their results and interpretations.
Sensorimotor cortical-subthalamic network dynamics during force generation
Authors: Alhourani Ahmad , Korzeniewska Anna , Wozny Thomas A. , Lipski Witold J. , Kondylis Efstathios D. , Ghuman Avniel S. , Crone Nathan E. , Crammond Donald J. , Turner Robert S. , Richardson R. Mark 
Published: April 2018

AbstractThe subthalamic nucleus (STN) is proposed to participate in pausing, or alternately, in dynamic scaling of behavioral responses, roles that have conflicting implications for understanding STN function in the context of deep brain stimulation (DBS) therapy. To examine the nature of event-related STN activity and subthalamic-cortical dynamics, we performed primary motor and somatosensory electrocorticography while subjects (n=10) performed a grip force task during DBS implantation surgery. The results provide the first evidence from humans that STN gamma activity can predict activity in the cortex both prior to and during movement, consistent with the idea that the STN participates in both motor planning and execution. We observed that STN activity appeared to facilitate movement: while both movement onset and termination both coincided with STN-cortical phase-locking, narrow-band gamma power was positively correlated with grip force, and event-related causality measures demonstrated that STN gamma activity predicted cortical gamma activity during movement. STN participation in somatosensory integration also was demonstrated by casual analysis. Information flow from the STN to somatosensory cortex was observed for both beta and gamma range frequencies, specific to particular movement periods and kinematics. Interactions in beta activity between the STN and somatosensory cortex, rather than motor cortex, predicted PD symptom severity. Thus, the STN contributes to multiple aspects of sensorimotor behavior dynamically across time.
The Italian Autism Network (ITAN): A Resource for Molecular Genetics and Biomarker Investigations
Authors: Muglia Pierandrea , Filosi Michele , Ros Lucio Da , Kam-Thong Tony , Nardocci Franco , Trabetti Elisabetta , Ratti Emiliangelo , Rizzini Paolo , Zuddas Alessandro , Bernardina Bernardo Dalla , Domenici Enrico ,   the Italian Autism Network
Published: April 2018

AbstractBackgroundA substantial genetic component accounts for Autism Spectrum Disorders (ASD) aetiology, with some rare and common genetic risk factors recently identified. Large collections of DNAs from thoroughly characterized ASD families are an essential step to confirm genetic risk factors, identify new variants and investigate genotype-phenotype correlations. The Italian Autism Network aimed at constituting a clinical database and a biorepository of samples derived from ASD subjects and first-degree relatives extensively and consistently characterized by child psychiatry centers in Italy.MethodsThe study was approved by the ethical committee of the University of Verona, the coordinating site, and by the local ethical committees of each recruiting site. Certified staff was specifically trained at each site for the overall study conduct, for clinical protocol administration and handling of biological material. A centralized database was developed to collect clinical assessment and medical records from each recruiting site. Children were eligible for recruitment based on the following inclusion criteria: age 4–18 years, at least one parent or legal guardian giving voluntary written consent, meeting DSM-IV criteria for Autistic Disorder or Asperger’s Disorder or Pervasive Developmental Disorder NOS. Affected individuals were assessed by full psychiatric, neurological and physical examination, evaluation with ADI-R and ADOS scales, cognitive assessment with Wechsler Intelligence Scale for Children or Preschool and Primary, Leiter International Performance Scale or Griffiths Mental Developmental Scale. Additional evaluations included language assessment, the Krug Asperger’s Disorder Index, and instrumental examination such as EEG and structural MRI. DNA, RNA and plasma were collected from eligible individuals and relatives. A central laboratory was established to host the biorepository, perform DNA and RNA extraction and lymphocytes immortalisation.
DiscussionThe study has led to an extensive collection of biological samples associated with standardised clinical assessments from a network of expert clinicians and psychologists. Eighteen sites have received ADI/ADOS training, thirteen of which have been actively recruiting. The clinical database currently includes information on 812 individuals from 249 families, and the biorepository has samples for 98% of the subjects. This effort has generated a highly valuable resource for conducting clinical and genetic research of ASD, amenable to further expansion.
Differential alteration of IL-8 in liver cancer stem cell enrichment in response to PI3K/Akt/mTOR inhibitors and sorafenib
Authors: Kahraman Deniz Cansen , Kahraman Tamer , Atalay Rengul Cetin 
Published: April 2018

AbstractLiver cancer stem cells (LCSCs) are derived from damaged and transformed Hepatic progenitor cells (HPCs) during precancerous cirrhosis stage. Ras/Raf/MAPK and PI3K/AKT/mTOR signaling pathways are significantly deregulated in liver cancer. The activation of PI3K/AKT/mTOR pathway in LCSC population is one of the reasons for acquired resistance to Sorafenib in advanced Hepatocellular carcinoma (HCC) patients. Therefore, identifying novel inhibitors targeting this pathway acting on LCSCs is highly essential. We therefore elucidated the bioactivities of small molecule kinase inhibitors on LCSCs acting through PI3K/Akt/mTOR pathway in comparison with DAPT (CSC inhibitor), DNA intercalators and Sorafenib. For this purpose, CD133+/EpCAM+ cells originated from HCC cells were analyzed by flow cytometry and effective inhibitors on LCSCs were further tested for their potential combinatorial effects. Treatment of cells with Sorafenib, and DNA intercalators resulted in enrichment of CD133+/EpCAM+ cells. Yet, mTOR inhibitor Rapamycin, and Notch pathway inhibitor DAPT significantly reduced CD133/EpCAM positivity. Combination studies revealed that sequential treatment strategy, which involves treatment of cells with Rapamycin prior to Sorafenib treatment, decreased the ratio of LCSCs as opposed to Sorafenib treatment alone or Sorafenib treatment prior to Rapamycin. The effect of the inhibitors were also demonstrated with LCSC sphere formation. Additionaly, a large panel of genes involved in cancer pathways were analyzed using Nanostring®nCounter®Technology to identify the differentially expressed genes in Rapamycin, Sorafenib or DAPT treated cells. Pathways involved in stemness (Wnt and Notch pathways) were differentially regulated between Rapamycin or DAPT treated cells and Sorafenib treated cells. Interleukin 8 (IL-8), FLNC, FLNA expressions were down-regulated upon treatment with DAPT or Rapamycin, yet up-regulated upon Sorafenib treatment. Following IL-8 inhibition CD133/EpCAM positivity of cells decreased significantly, indicating that IL-8 signaling is crucial for the conservation of stemness features of cancer cells.ConclusionPI3K/Akt/mTOR pathway inhibitors alter hepatic CSC composition and gene expression in favor or to the detriment of cancer stem cell survival. Blockade of IL-8 signaling provides a promising therapeutic approach for prevention of LCSC enrichment.
Co-evolution networks of HIV/HCV are modular with direct association to structure and function
Authors: Quadeer Ahmed Abdul , Morales-Jimenez David , McKay Matthew R. 
Published: April 2018

AbstractMutational correlation patterns found in population-level sequence data for the Human Immunodeficiency Virus (HIV) and the Hepatitis C Virus (HCV) have been demonstrated to be informative of viral fitness. Such patterns can be seen as footprints of the intrinsic functional constraints placed on viral evolution under diverse selective pressures. Here, considering multiple HIV and HCV proteins, we demonstrate that these mutational correlations encode a modular co-evolutionary structure that is tightly linked to the structural and functional properties of the respective proteins. Specifically, by introducing a robust statistical method based on sparse principal component analysis, we identify near-disjoint sets of collectively-correlated residues (sectors) having mostly a one-to-one association to largely distinct structural or functional domains. This suggests that the distinct phenotypic properties of HIV/HCV proteins often give rise to quasi-independent modes of evolution, with each mode involving a sparse and localized network of mutational interactions. Moreover, individual inferred sectors of HIV are shown to carry immunological significance, providing insight for guiding targeted vaccine strategies.Author summaryHIV and HCV cause devastating infectious diseases for which no functional vaccine exists. A key problem is that while immune cells may induce individual mutations that compromise viral fitness, this is typically restored through other “compensatory” mutations, leading to immune escape. These compensatory pathways are complicated and remain poorly understood. They do, however, leave co-evolutionary markers which may be inferred from measured sequence data. Here, by introducing a new robust statistical method, we demonstrated that the compensatory networks employed by both viruses exhibit a remarkably simple decomposition involving small and near-distinct groups of protein residues, with most groups having a clear association to biological function or structure. This provides insights that can be harnessed for the purpose of vaccine design.
Ethane-dependent synthesis of polyhydroxyalkanoates by the obligate methanotrophMethylocystis parvusOBBP
Authors: Jaewook Myung , Flanagan James C. A. , Galega Wakuna M. , Waymouth Robert M. , Criddle Craig S. 
Published: April 2018

ABSTRACTUnder conditions of nutrient-limited growth, Type II obligate methanotrophs oxidize C1compounds, such as methane or methanol and accumulate intracellular granules of poly(3-hydroxybutyrate) (P3HB). Here, we report that, under same nutrient-limited conditions, the Type II obligate methanotrophMethylocystis parvusOBBP can use ethane as its sole carbon and energy source for synthesis P3HB granules, accumulating up to 35 ± 4 wt% P3HB.13C-NMR spectra of the P3HB confirmed incorporation of13C from [13C2]ethane. Moreover, when valerate was added as a co-substrate with ethane, oxidation of the ethane supported synthesis of the copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV).IMPORTANCEThe presence of ethane in natural gas is often considered undesirable for methanotroph-based biotechnology due to the C1specialization of obligate methanotrophs and concerns about inhibitory byproducts arising from methane monooxygenase-mediated cometabolism of ethane. This work establishes that co-oxidation of ethane and further metabolism in the absence of methane can support synthesis of the valuable polyhydroxyalkanoate bioplastics P3HB and PHBV.
NLMR and landscapetools: An integrated environment for simulating and modifying neutral landscape models in R
Authors: Sciaini Marco , Fritsch Matthias , Scherer Cédric , Simpkins Craig Eric 
Published: April 2018

AbstractNeutral landscape models (NLMs) simulate landscape patterns based on theoretical distributions and can be used to systematically study the effect of landscape structure on ecological processes. NLMs are commonly used in landscape ecology to enhance the findings of field studies as well as in simulation studies to provide an underlying landscape. However, their creation so far has been limited to software that is platform dependent, does not allow a reproducible workflow or is not embedded in R, the prevailing programming language used by ecologists.Here, we present two complementary R packages NLMR and land-scapetools, that allow users to generate, manipulate and analyse NLMs in a single environment. They grant the simulation of the widest collection of NLMs found in any single piece of software thus far while allowing for easy manipulation in a self-contained and reproducible workflow. The combination of both packages should stimulate a wider usage of NLMs in landscape ecology. NLMR is a comprehensive collection of algorithms with which to simulate NLMs. landscapetools provides a utility toolbox which facilitates an easy workflow with simulated neutral landscapes and other raster data.We show two example applications that illustrate potential use cases for NLMR and landscapetools: First, an agent-based simulation study in which the effect of spatial structure on disease persistence was studied. Here, spatial heterogeneity resulted in more variable disease outcomes compared to the common well-mixed host assumption. The second example shows how increases in spatial scaling can introduce biases in calculated landscape metrics.Simplifying the workflow around handling NLMs should encourage an uptake in the usage of NLMs. NLMR and landscapetools are both generic frameworks that can be used in a variety of applications and are a further step to having a unified simulation environment in R for answering spatial research questions.