bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain and Sedation Management: 2018 Update for the Rogers’ Textbook of Pediatric Intensive Care
Authors: Walker Tracie , Kudchadkar Sapna R. 
Published: October 2018

Objectives:
To review important articles on pain, sedation, sleep, and delirium in the field of pediatric critical care published subsequent to the fifth edition of the Rogers’ Textbook of Pediatric Critical Care.

Data Sources:
The U.S. National Library of Medicine PubMed was searched for a combination of the term “pediatric” and the following terms: “sedation,” “sedation protocol,” “pain,” “pain score,” “neuromuscular blockade,” “delirium,” and “sleep.” Titles and abstracts resulting from the search were screened for full-text review and potential inclusion. Authors also included recent key articles they were aware of with direct relevance to the topics.

Study Selection and Data Extraction:
The authors selected articles for inclusion based on their relevance and clinical significance if they were published subsequent to the fifth edition of the textbook.

Data Synthesis:
Selected articles were grouped together by categories similar to specific sections of the pain and sedation chapter in the textbook and included pain, sedation, sleep, and delirium.

Conclusions:
Recent research into pediatric pain and sedation management has focused on optimizing the choice of sedative medications, in particular by increasing the use and understanding of nonopioid and nonbenzodiazepine options such as ketamine and alpha-2 agonists. Delirium has emerged as a significant morbidity in the critically ill pediatric patient, and recent articles have concentrated on the use of validated screening tools to determine the epidemiology and risk factors in specific populations, including patients with cardiac disease and those receiving extracorporeal membrane oxygenation. A consistent theme in the most recent literature is the role of titrated but effective sedation, quality improvement to increase delirium recognition, and optimizing the pediatric intensive care environment to promote sleep.
Corticosteroid Tapering Regimens in Rheumatic Disease
Authors: Campbell Ashley M. , Martin Jennifer R. , Erstad Brian L. 
Published: October 2018

Background/Objective
Corticosteroids have long been used to effectively treat rheumatic disorders, but adverse effects associated with extended-duration regimens generate disagreement among clinicians regarding optimal tapering strategies. The objective of this systematic review was to assess clinical outcomes of differing tapering regimens after corticosteroid monotherapy in adults with rheumatic disorders.

Methods
A systematic review of Medline/PubMed, Embase, Cochrane, International Pharmaceutical Abstracts, Web of Science, Scopus, Global Index Medicus, American College of Rheumatology, gray literature, and reference lists up to June 27, 2018, was conducted by 2 authors. Randomized controlled trials, case-control studies, and prospective observational studies comparing at least 2 tapering strategies of medium- to high-dose (>7.5 mg but ≤100 mg oral prednisone equivalent daily), extended-duration (≥10 days) corticosteroids were included if they reported at least 1 efficacy and 1 adverse effect parameter.

Results
Two studies met criteria for the review, which included 62 patients. One study examined a prednisolone versus a modified release prednisone taper for giant cell arteritis and suggested 80% (n = 4) and 85.7% (n = 6) remission rates, respectively, at 26 weeks. The other study examined a methylprednisolone versus a prednisone taper for polymyalgia rheumatica and reported 100% and 89% remission rates, respectively, at 26 weeks. Adverse effects reported between the 2 studies included sleep, hyperglycemia, infection, and fractures. However, the studies were not powered to detect differences in these outcomes.

Conclusions
There is no high-level evidence to guide tapering until discontinuation after extended courses of medium- to high-dose treatment regimens, as current guidelines rely heavily on expert opinion and small case series with a trial-and-error approach. This review supports the need for additional research to shift tapering recommendations to a more evidence-based practice.
Characterization of Diffuse Gliomas With Histone H3-G34 Mutation by MRI and Dynamic 18F-FET PET
Authors: Vettermann Franziska J. , Felsberg Jörg , Reifenberger Guido , Hasselblatt Martin , Forbrig Robert , Berding Georg , la Fougère Christian , Galldiks Norbert , Schittenhelm Jens , Weis Joachim , Albert Nathalie L. , Schüller Ulrich 
Published: October 2018

Background
Recent data suggest that diffuse gliomas carrying mutations in codon 34 of the H3 histone family 3A protein represent a very rare, distinct subgroup of IDH–wild type malignant astrocytic gliomas. However, characteristics detectable by MRI and 18F-FET PET in H3-G34-mutant gliomas are unknown.

Methods
We report on MRI and 18F-FET PET findings in 8 patients from 4 German centers with H3-G34-mutant diffuse gliomas. MRI analyses included multifocality, contrast enhancement, necrosis, cysts, hemorrhages, calcification, and edema. 18F-FET PET characteristics were evaluated on the basis of static 18F-FET PET parameters, such as maximal tumor-to-background ratio (TBRmax) and biological tumor volume (BTV), as well as the minimal time-to-peak (TTPmin) obtained from dynamic 18F-FET PET data.

Results
MRI showed multifocal lesions in 2 of 8, contrast enhancement in 6 of 8, necrosis in 3 of 8, cysts in 3 of 8, hemorrhage in 1 of 8, and calcifications in 1 of 8 patients. None of the tumors showed marked peritumoral edema. However, all 8 H3-G34-mutant gliomas were characterized by a high uptake intensity on 18F-FET PET with a median TBRmax of 3.4 (range, 2.5–11.7) and a relatively diffuse uptake pattern leading to a large BTV (median, 41.9 mL; range, 7.5–115.6). Dynamic PET data revealed a short median TTPmin of 12.5 minutes.

Conclusions
MRI features of diffuse gliomas with H3-G34 mutation may present very heterogeneously with some cases not even fulfilling the imaging criteria of high-grade glioma. In contrast, in 18F-FET PET, these tumors show an extensive and diffuse tracer uptake resulting in large BTV with a high TBRmax and a short TTPmin, thus resembling PET characteristics of aggressive high-grade gliomas, namely, glioblastomas.
The reappearance of Galileo's original Letter to Benedetto Castelli
Authors: Camerota Michele , Giudice Franco , Ricciardo Salvatore 
Published: October 2018

This article describes an important manuscript discovered recently in the Royal Society archives, and presents evidence that it is the holograph of Galileo's
Letter to Benedetto Castelli
of 21 December 1613. It was in this letter that Galileo first set out his ideas on the relation between science and religion, and defended Copernican astronomy from charges of being contrary to the Holy Scriptures. The text of the
Letter
has hitherto been known only through manuscript copies, namely the 12 used by Antonio Favaro in his critical edition of 1895. Despite his magisterial work, Favaro did not manage to locate Galileo's autograph and was forced to rely exclusively on copies. The
Letter to Castelli
preserved at the Royal Society is of remarkable interest. By comparison with the other extant manuscript copies by different hands, its wording seems to be theologically more daring and compromising. The discovery of this autograph is therefore one of the most important in Galilean studies in recent decades, shedding new light on his intricate relations with the Roman Catholic Church in these years.
A set of functionally-defined brain regions with improved representation of the subcortex and cerebellum
Authors: Seitzman Benjamin A. , Gratton Caterina , Marek Scott , Raut Ryan V. , Dosenbach Nico U.F. , Schlaggar Bradley L. , Petersen Steven E. , Greene Deanna J. 
Published: October 2018

AbstractAn important aspect of network-based analysis is robust node definition. This issue is critical for functional brain network analyses, as poor node choice can lead to spurious findings and misleading inferences about functional brain organization. Two sets of functional brain nodes from our group are well represented in the literature: (1) 264 volumetric regions of interest (ROIs) reported in Power et al., 2011 and (2) 333 cortical surface parcels reported in Gordon et al., 2016. However, subcortical and cerebellar structures are either incompletely captured or missing from these ROI sets. Therefore, properties of functional network organization involving the subcortex and cerebellum may be underappreciated thus far. Here, we apply a winner-take-all partitioning method to resting-state fMRI data to generate novel functionally-constrained ROIs in the thalamus, basal ganglia, amygdala, hippocampus, and cerebellum. We validate these ROIs in three datasets using several criteria, including agreement with existing literature and anatomical atlases. Further, we demonstrate that combining these ROIs with established cortical ROIs recapitulates and extends previously described functional network organization. This new set of ROIs is made publicly available for general use, including a full list of MNI coordinates and functional network labels.
DNA barcodes for rapid, whole genome, single-molecule analyses
Authors: Wand Nathaniel , Smith Darren A. , Wilkinson Andrew , Rushton Ashleigh , Busby Stephen J. W. , Styles Iain , Neely Robert K. 
Published: October 2018

ABSTRACTWe report an approach for visualizing DNA sequence and using these ‘DNA barcodes’ to search complex mixtures of genomic material for DNA molecules of interest. We demonstrate three applications of this methodology; by identifying specific molecules of interest from a dataset containing gigabasepairs of genome; by straightforward strain-typing of bacteria from such a dataset and, finally, by locating infecting virus molecules in a background of human genomic material. DNA barcodes enable quantitative understanding of complex genome mixtures, on a large scale. As a result of the dense fluorescent labelling of the DNA, individual barcodes of the order 40 kilobase pairs in length can be reliably identified. This means DNA can be prepared for imaging using standard handling and purification techniques. The recorded dataset provides stable physical and electronic records of the total genomic content of a sample that can be readily searched for a molecule or region of interest.
Modelling cancer progression using Mutual Hazard Networks
Authors: Schill Rudolf , Solbrig Stefan , Wettig Tilo , Spang Rainer 
Published: October 2018

AbstractMotivationCancer progresses by accumulating genomic events, such as mutations and copy number alterations, whose chronological order is key to understanding the disease but difficult to observe. Instead, cancer progression models use co-occurence patterns in cross-sectional data to infer epistatic interactions between events and thereby uncover their most likely order of occurence. State-of-the-art progression models, however, are limited by mathematical tractability and only allow events to interact in directed acyclic graphs, to promote but not inhibit subsequent events, or to be mutually exclusive in distinct groups that cannot overlap.ResultsHere we propose Mutual Hazard Networks (MHN), a new Machine Learning algorithm to infer cyclic progression models from cross-sectional data. MHN model events by their spontaneous rate of fixation and by multiplicative effects they exert on the rates of successive events. MHN compared favourably to acyclic models in cross-validated model fit on four datasets tested. In application to the glioblastoma dataset from The Cancer Genome Atlas, MHN proposed a novel interaction in line with consecutive biopsies: IDH1 mutations are early events that promote subsequent fixation of TP53 mutations.AvailabilityImplementation and data are available at https://github.com/RudiSchill/MHN.
The impact of tumor stromal architecture on therapy response and clinical progression
Authors: Altrock Philipp M. , Yoon Nara , Bull Joshua A. , Wu Hao , Ruiz-Ramírez Javier , Miroshnychenko Daria , Kimmel Gregory J. , Kim Eunjung , Vander Velde Robert J. , Rejniak Katarzyna , Manley Brandon J. , Spill Fabian , Marusyk Andriy 
Published: October 2018

Abstract— Advances in molecular oncology research culminated in the development of targeted therapies that act on defined molecular targets either on tumor cells directly (such as inhibitors of oncogenic kinases), or indirectly by targeting the tumor microenvironment (such as anti-angiogenesis drugs). These therapies can induce strong clinical responses, when properly matched to patients. Unfortunately, most targeted therapies ultimately fail as tumors evolve resistance. Tumors consist not only of neoplastic cells, but also of stroma, whereby “stroma” is the umbrella term for non-tumor cells and extracellular matrix (ECM) within the tumor microenvironment, possibly excluding immune cells1. We know that tumor stroma is an important player in the development of resistance. We also know that stromal architecture is spatially complex, differs from patient to patient and changes with therapy. However, to this date we do not understand the link between spatial and temporal changes in stromal architecture and response of tumors to therapy, in space and time. In this project we sought to address this gap of knowledge using a combination of mathematical and statistical modeling, experimental in vivo studies, and analysis of clinical samples in therapies that target tumor cells directly (in lung and breast cancers) and indirectly (in kidney cancer). This knowledge will inform therapy choices and offer new angles for therapeutic interventions. Our main question is: how does spatial architecture of stroma impact the emergence or evolution of resistance to targeted therapies, and how can we use this knowledge clinically?
Mathematical Modeling Identifies the Role of Adaptive Immunity as a Key Controller of Respiratory Syncytial Virus (RSV) Titer in Cotton Rats
Authors: Wethington Darren , Harder Olivia , Uppulury Karthik , Stewart William C. L. , Chen Phylip , King Tiffany , Reynolds Susan D. , Peeples Mark E. , Niewiesk Stefan , Das Jayajit 
Published: October 2018

AbstractRespiratory syncytial virus (RSV) is a common virus that can have varying effects ranging from mild cold-like symptoms to mortality depending on the age and immune status of the individual. We combined mathematical modeling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well differentiated human airway epithelial (HAE) culturesin vitroand in immunocompetent and immunosuppressed cotton rats to glean mechanistic details that underlie RSV infection kinetics in the lung. Quantitative analysis of viral titer kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titer kinetic features including a faster time scale of viral titer clearance than viral production, and a monotonic decrease in the peak RSV titer with decreasing inoculum dose. Parameter estimation in the ODE model using a non-linear mixed effects approach revealed a very low rate (average single cell lifetime > 10 days) of cell lysis by RSV before the adaptive immune response is initiated. Our model predicted negligible changes in the RSV titer kinetics on earlier days (< 5 d.p.i) but a slower decay in RSV titer at later days (>5 d.p.i) in immunosuppressed cotton rats compared to that in non-suppressed cotton ratsin silico.These predictions were in excellent agreement with the experimental results. Our combined approach quantified the importance of the adaptive immune response in suppressing RSV infection in cotton rats, which could be useful in testing RSV vaccine candidates.ImportanceA major difficulty in developing vaccines against RSV infection is our rudimentary understanding of the mechanisms that underlie RSV infection. We addressed this challenge by developing a mechanistic computational model with predictive powers for describing RSV infection kinetics in cotton rats. The model was constructed synergistically within vitroandin vivomeasurements. The combined framework determined an important role for CD8+ T cells responses in reducing RSV titers in cotton rats. The framework can be used to design future experiments to elucidate mechanisms underlying RSV infection and test outcomes for potential vaccine candidates. In addition, estimation of the model parameters provides quantitative values for parameters of biological and clinical interest such as the replication rate of RSV, the death rate of infected cells, and the average number of new infections initiated by a single infected cell.
Simultaneous task-based BOLD-fMRI and [18-F] FDG functional PET for measurement of neuronal metabolism in the human visual cortex
Authors: Jamadar Sharna D , Ward Phillip GD , Li Shenpeng , Sforazzini Francesco , Baran Jakub , Chen Zhaolin , Egan Gary F 
Published: October 2018

AbstractStudies of task-evoked brain activity are the cornerstone of cognitive neuroscience, and unravel the spatial and temporal brain dynamics of cognition in health and disease. Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is one of the most common methods of studying brain function in humans. BOLD-fMRI indirectly infers neuronal activity from regional changes in blood oxygenation and is not a quantitative metric of brain function. Regional variation in glucose metabolism, measured using [18-F] fluorodeoxyglucose positron emission tomography (FDG-PET), provides a more direct and interpretable measure of neuronal activity. However, while the temporal resolution of BOLD-fMRI is in the order of seconds, standard FDG-PET protocols provide a static snapshot of glucose metabolism. Here, we develop a novel experimental design for measurement of task-evoked changes in regional blood oxygenation and glucose metabolism with high temporal resolution. Over a 90-min simultaneous BOLD-fMRI/FDG-PET scan, [18F] FDG was constantly infused to 10 healthy volunteers, who viewed a flickering checkerboard presented in a hierarchical block design. Dynamic task-related changes in blood oxygenation and glucose metabolism were examined with temporal resolution of 2.5sec and 1-min, respectively. Task-related, temporally coherent brain networks of haemodynamic and metabolic connectivity were maximally related in the visual cortex, as expected. Results demonstrate that the hierarchical block design, together with the infusion FDG-PET technique, enabled both modalities to track task-related neural responses with high temporal resolution. The simultaneous MR-PET approach has the potential to provide unique insights into the dynamic haemodynamic and metabolic interactions that underlie cognition in health and disease.
Rapid, Affordable, Collection and Analysis of Bioaerosol Viral Pathogen (Begomoviruses and Whitefly Vectors)
Authors: Hunter Wayne B. , McKenzie Cindy L. , Mitchell Bailey W. 
Published: October 2018

AbstractDetection of pathogens is critical to monitoring their distribution and spread, and is a key component in the prediction and management of disease epidemiology. Monitoring for pathogens as bioaerosols requires developing techniques which are sensitive, affordable, and time saving before they will have widespread impact. This approach also overcomes private property issues, which are a major pitfall in monitoring diseases in complex agricultural and urban settings. In this study, we have applied an emerging technology of electrostatic sampling to the detection of an insect-transmitted plant pathogen as a bioaerosol. Where insects aggregate in large numbers, as with whiteflies, leafhoppers, psyllids and honey bees, the pathogen (ie. virus or bacteria) becoming aerosolized as thousands of excreta droplets fall from the plants during feeding. Agricultural systems have not fully measured the impact of bioaerosols on disease epidemiology. Electrostatic sampling provides a valuable, affordable, method for monitoring for diseases as bioaerosols, which includes plant, animal and human pathogens. This study shows results which successfully used an electrostatic sampling device to collect an aerosolized begomovirus from the air near whiteflies feeding on virus-infected tomato plants.
Identifying neurophysiological features associated with anesthetic state in newborn mice and humans
Authors: Chini Mattia , Gretenkord Sabine , Kostka Johanna K. , Pöpplau Jastyn A. , Cornelissen Laura , Berde Charles B. , Hanganu-Opatz Ileana L. , Bitzenhofer Sebastian H. 
Published: October 2018

One Sentence SummaryMachine learning reveals consistent features of anesthetic states assessed by intracranial recordings in newborn mice and multichannel EEG in human neonates and infants.AbstractMonitoring the hypnotic component of anesthesia during surgeries is critical to prevent intraoperative awareness and reduce adverse side effects. For this purpose, electroencephalographic methods complementing measures of autonomic functions and behavioral responses are in use in clinical practice. However, in human neonates and infants existing methods may be unreliable and the correlation between brain activity and anesthetic depth is still poorly understood. Here, we characterize the effects of different anesthetics on activity of several brain areas in neonatal mice and develop machine learning approaches to identify electrophysiological features predicting inspired or end-tidal anesthetic concentration as a proxy for anesthetic depth. We show that similar features from electroencephalographic recordings can be applied to predict anesthetic concentration in neonatal mice, and human neonates and infants. These results might support a novel strategy to monitor anesthetic depth in human newborns.
Effect of ring topology in a stochastic model for Z-ring dynamics in bacteria
Authors: Sumedha A. Swain , Kumar A. V. A 
Published: October 2018

AbstractUnderstanding the mechanisms responsible for dynamics of theZ-ring is important for our understanding of cell division in prokaryotic cells. In this work, we present a minimal stochastic model that qualititatively reproduces observations of polymerization, of formation of dynamic contractile ring that is stable for a long time and of depolymerization shown by FtsZ polymer. We explore different mechanisms for ring breaking and hydrolysis. Hydrolysis is known to regulate the dynamics of other tubulin polymers like microtubules. We find that the presence of the ring allows for an additional mechanism for regulating the dynamics of FtsZ polymers. Ring breaking dynamics in the presence of hydrolysis naturally induce rescue and catastrophe events, irrespective of the mechanism of hydrolysis. Based on our model, we conclude that theZ-ring undergoes random breaking and closing during the process of cell division.