bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towers of Nodal Bubbles for the Bahri–Coron Problem in Punctured Domains
Authors: Clapp Mónica , Faya Jorge , Pacella Filomena 
Published: November 2017

Abstract
Let Ω be a bounded smooth domain in $\mathbb {R}^{N}$ which contains a ball of radius R centered at the origin, N ≥ 3. Under suitable symmetry assumptions, for each δ ∈ (0, R), we establish the existence of a sequence (um, δ) of nodal solutions to the critical problem $$\begin{align*}-\Delta u=|u|^{2^{\ast}-2}u\text{ in }\Omega_{\delta}:=\{x\in\Omega :\left\vert x\right\vert>\delta\},\quad u=0\text{ on }\partial \Omega_{\delta},\nonumber\end{align*}$$ where $2^{\ast }:=\frac {2N}{N-2}$ is the critical Sobolev exponent. We show that, if Ω is strictly star-shaped then, for each $m\in \mathbb {N},$ the solutions um, δ concentrate and blow up at 0, as $\delta \rightarrow 0,$ and their limit profile is a tower of nodal bubbles, that is, it is a sum of rescaled nonradial sign-changing solutions to the limit problem $$\begin{align*}-\Delta u=|u|^{2^{\ast}-2}u, \quad u\in D^{1,2}(\mathbb{R}^{N}),\nonumber\end{align*}$$ centered at the origin.
The burden of presumed tuberculosis in hospitalized children in a resource-limited setting in Papua New Guinea: a prospective observational study
Authors: Watch Villa , Aipit Jimmy , Kote-Yarong Tina , Rero Allanie , Bolnga John W , Lufele Elvin , Laman Moses 
Published: November 2017

Abstract

Background
In Papua New Guinea, TB is considered to be a major public health problem, but little is known about the prevalence and prognosis of presumed TB in children.

Methods
As part of a prospective hospital-based surveillance on the northern coast of mainland Papua New Guinea, the authors investigated the admission prevalence and case fatality rate associated with presumed TB over a 6-year period (2011–2016). All children admitted who were diagnosed with TB were followed-up until discharge or death.

Results
Of 8992 paediatric admissions, 734 patients (8.2%) were diagnosed with presumed TB and there were 825 deaths, with TB accounting for 102 (12.4%). Extrapulmonary TB was the final diagnosis in 384 admissions {prevalence 4.3% [384/8992 (95% CI 3.9–4.7)]} with a case fatality rate of 21.4% [82/384 (95% CI 17.4–25.9)]. TB meningitis, disseminated TB and pericardial TB had high case fatality rates of 29.0% (53/183), 28.9% (11/38) and 25% (4/16), respectively. Severe malnutrition was more common in patients with pulmonary compared with extrapulmonary TB (25.4% vs 15.6%; p&lt;0.01).

Conclusions
Improved community-based case detection strategies, routine BCG vaccinations and other effective forms of TB control need revitalization and sustainability to reduce the high case fatality rates associated with childhood TB in Papua New Guinea.
A value set for documenting adverse reactions in electronic health records
Authors: Goss Foster R , Lai Kenneth H , Topaz Maxim , Acker Warren W , Kowalski Leigh , Plasek Joseph M , Blumenthal Kimberly G , Seger Diane L , Slight Sarah P , Wah Fung Kin , Chang Frank Y , Bates David W , Zhou Li 
Published: November 2017

Abstract

Objective
To develop a comprehensive value set for documenting and encoding adverse reactions in the allergy module of an electronic health record.

Materials and Methods
We analyzed 2 471 004 adverse reactions stored in Partners Healthcare’s Enterprise-wide Allergy Repository (PEAR) of 2.7 million patients. Using the Medical Text Extraction, Reasoning, and Mapping System, we processed both structured and free-text reaction entries and mapped them to Systematized Nomenclature of Medicine – Clinical Terms. We calculated the frequencies of reaction concepts, including rare, severe, and hypersensitivity reactions. We compared PEAR concepts to a Federal Health Information Modeling and Standards value set and University of Nebraska Medical Center data, and then created an integrated value set.

Results
We identified 787 reaction concepts in PEAR. Frequently reported reactions included: rash (14.0%), hives (8.2%), gastrointestinal irritation (5.5%), itching (3.2%), and anaphylaxis (2.5%). We identified an additional 320 concepts from Federal Health Information Modeling and Standards and the University of Nebraska Medical Center to resolve gaps due to missing and partial matches when comparing these external resources to PEAR. This yielded 1106 concepts in our final integrated value set. The presence of rare, severe, and hypersensitivity reactions was limited in both external datasets. Hypersensitivity reactions represented roughly 20% of the reactions within our data.

Discussion
We developed a value set for encoding adverse reactions using a large dataset from one health system, enriched by reactions from 2 large external resources. This integrated value set includes clinically important severe and hypersensitivity reactions.

Conclusion
This work contributes a value set, harmonized with existing data, to improve the consistency and accuracy of reaction documentation in electronic health records, providing the necessary building blocks for more intelligent clinical decision support for allergies and adverse reactions.
Incidence and Predictive Factors of Sepsis Following Adult Spinal Deformity Surgery
Authors: Zuckerman Scott L , Lakomkin Nikita , Stannard Blaine P , Hadjipanayis Constantinos G , Shaffrey Christopher I , Smith Justin S , Cheng Joseph S 
Published: November 2017

Abstract

BACKGROUND
Surgery for adult spinal deformity (ASD) improves quality of life, yet morbidity is high. Sepsis is a challenging postoperative complication that can result in death and drive inpatient resources.

OBJECTIVE
To identify the incidence and risk factors for development of sepsis within 30 days following ASD surgery.

METHODS
Adult patients who underwent thoracolumbar spinal deformity correction between 2008 and 2014 were identified in the National Surgical Quality Improvement Program database. Demographic and operative variables were extracted. The primary outcome was development of postoperative sepsis. Multivariable logistic regression modeling was used to identify independent risk factors for sepsis.

RESULTS
A total of 6158 patients underwent ASD surgery. Of these, 156 (2.5%) developed sepsis postoperatively. Independent risk factors included operative time (odds ratio [OR]: 1.004, 95% confidence interval [CI]: 1.003-1.005, P < .001), male sex (OR: 1.47, 95% CI: 1.05-2.05, P = .023), diabetes (OR: 1.59, 95% CI: 1.05-2.40, P = .027), functional dependency (OR: 1.82, 95% CI: 1.12-2.95, P = .015), weight loss (OR: 2.45, 95% CI: 1.04-5.78, P = .040), bleeding disorder (OR: 2.58, 95% CI: 1.34-4.93, P = .004), and ascites (OR: 56.11, 95% CI: 5.01-628.50, P = .001). This model demonstrated strong predictive capacity, with an area under the curve of 0.80. Patients who developed sepsis were significantly more likely to have a prolonged hospital stay (P < .001), be readmitted (P < .001), and die (P < .001). The median (range) time to sepsis was 9 d (0-30).

CONCLUSION
In patients undergoing ASD surgery, male sex, diabetes, ascites, bleeding disorder, functional dependency, excessive weight loss and increased operative time independently predicted sepsis. This perioperative patient profile can be used for preoperative risk assessment, patient counseling, and postoperative management for patients undergoing ASD surgery.
FireCloud, a scalable cloud-based platform for collaborative genome analysis: Strategies for reducing and controlling costs
Authors: Birger Chet , Hanna Megan , Salinas Edward , Neff Jason , Saksena Gordon , Livitz Dimitri , Rosebrock Daniel , Stewart Chip , Leshchiner Ignaty , Baumann Alexander , Voet Douglas , Cibulskis Kristian , Banks Eric , Philippakis Anthony , Getz Gad 
Published: November 2017

AbstractFireCloud, one of three NCI Cloud Pilots, is a collaborative genome analysis platform built on a cloud computing infrastructure. FireCloud aims to solve the many challenges presented by the increasingly large data sets and computing requirements employed in cancer research. However, cost uncertainty associated with cloud computing’s pay-as-you-go model is proving to be a barrier to adoption of cloud computing. In this paper we present guidelines for optimizing workflows to minimize cost and reduce latency. Our guidelines include: (i) dynamic disk sizing to efficiently utilize virtual disks; (ii) tuned provisioning of virtual machines (VMs) using a performance monitoring tool; (iii) taking advantage of steep price discounts of preemptible VMs; and (iv) utilizing the optimal parallelization of a task’s workload.
Exploring variation in human papillomavirus vaccination uptake: multi-level spatial analysis
Authors: Riesen Maurane , Konstantinoudis Garyfallos , Lang Phung , Low Nicola , Hatz Christoph , Maeusezahl Mirjam , Spaar Anne , Bühlmann Marc , Spycher Ben D. , Althaus Christian L. 
Published: November 2017

AbstractBackgroundUnderstanding the factors that influence human papillomavirus (HPV) vaccination uptake is critically important to design effective vaccination programmes. In Switzerland, completed HPV vaccination by age 16 years among women ranges from 30 to 79% across 26 cantons (states). Our objective was to identify factors that are associated with the spatial variation in HPV vaccination uptake.Methods and findingsWe used data from the Swiss National Vaccination Coverage Survey 2009-2016 on HPV vaccination status (≥1 dose) of 14-17 year old girls, their municipality of residence and their nationality for 21 of 26 cantons (N=8,965). We examined covariates at municipality level: language, degree of urbanisation, socio-economic position, religious denomination, results of a vote about vaccination laws; and, at cantonal level, availability of school-based vaccination and survey period. We used a series of conditional auto regressive (CAR) models to assess the effects of covariates while accounting for variability between cantons and municipal-level spatial autocorrelation. In the best-fit model, school-based vaccination (adjusted odds ratio, OR: 2.51, 95% credible interval, CI: 1.77-3.56) was associated with increased uptake, while lower acceptance of vaccination laws was associated with lower HPV vaccination uptake (OR 0.61, 95% CI: 0.50-0.73). Overall, the covariates explained 88% of the municipal-level variation in uptake.ConclusionsIn Switzerland, cantons play a prominent role in the variation in HPV vaccination uptake, especially through the provision of school-based vaccination delivery. HPV vaccination uptake is also strongly associated with inhabitants’ attitudes towards vaccination. To increase uptake, efforts should be made both to mitigate vaccination scepticism and to encourage school-based vaccination.
Endodermal differentiation is reconstructed by coordination of two parallel signaling systems derived from the stele in roots
Authors: Li Pengxue , Yu Qiaozhi , Xu Chunmiao , Gu Xu , Qi Shilian , Wang Hong , Zhong Fenglin , Wu Shuang 
Published: November 2017

AbstractThe plant roots represent the exquisitely controlled cell fate map in which different cell types undergo a complete status transition from stem cell division and initial fate specification, to the terminal differentiation. The endodermis is initially specified in meristem but further differentiates to form Casparian strips (CSs), the apoplastic barrier in the mature zone for the selective transport between stele and outer tissues, and thus is regarded as plant inner skin. In the Arabidopsis thaliana root the transcription factors SHORTROOT (SHR) regulate asymmetric cell division in cortical initials to separate endodermal and cortex cell layer. In this paper, we utilized synthetic approach to examine the reconstruction of fully functional Casparian strips in plant roots. Our results revealed that SHR serves as a master regulator of a hierarchical signaling cascade that, combined with stele-derived small peptides, is sufficient to rebuild the functional CS in non-endodermal cells. This is a demonstration of the deployment of two parallel signaling systems, in which both apoplastic and symplastic communication were employed, for coordinately specifying the endodermal cell fate.
A potent neutralizing epitope of limited variability in the head domain of haemagglutinin as a novel influenza vaccine target
Authors: Thompson Craig P , Lourenço José , Walters Adam A , Obolski Uri , Edmans Matthew , Palmer Duncan S , Kooblall Kreepa , Carnell George W , Connor Daniel O’ , Bowden Thomas A , Pybus Oliver G , Pollard Andrew J , Temperton Nigel J , Lambe Teresa , Gilbert Sarah C , Gupta Sunetra 
Published: November 2017

AbstractAntigenic targets of influenza vaccination are currently seen to be polarised between (i) highly immunogenic (and protective) epitopes of high variability, and (ii) conserved epitopes of low immunogenicity. This requires vaccines directed against the variable sites to be continuously updated, with the only other alternative being seen as the artificial boosting of immunity to invariant epitopes of low natural efficacy. However, theoretical models suggest that the antigenic evolution of influenza is best explained by postulating the existence of highly immunogenic epitopes of limited variability. Here we report the identification of such an epitope of limited variability in the head domain of the H1 haemagglutinin protein. We show that the epitope mediates immunity to historical influenza strains not previously seen by a cohort of young children. Furthermore, vaccinating mice with these epitope conformations can induce immunity to all the human H1N1 influenza strains that have circulated since 1918. The identification of epitopes of limited variability offers a mechanism by which a universal influenza vaccine can be created; these vaccines would also have the potential to protect against newly emerging influenza strains.
Pydigree: a python library for manipulation and forward-time simulation and of genetic datasets
Authors: Hicks James E. 
Published: November 2017

AbstractThe development of software for working with data from population genetics or genetic epidemiology often requires substantial time spent implementing common procedures. Pydigree is a cross-platform Python 3 library that contains efficient, user friendly implementations for many of these common functions, and support for input from common file formats. Developers can combine the functions and data structures to rapidly implement programs handling genetic data. Pydigree presents a useful environment for development of applications for genetic data or rapid prototyping before reimplementation in a higher-performance language.Pydigree is freely available under an open source license. Stable sources can be found in the Python Package Index at https://pypi.python.org/pypi/pydigree/, and development sources can be downloaded at https://github.com/jameshicks/pydigree/
Propofol-Induced Unresponsiveness is Associated with Impaired Feedforward Connectivity in the Cortical Hierarchy
Authors: Sanders Robert D. , Banks Matthew I , Darracq Matthieu , Moran Rosalyn , Sleigh Jamie , Gosseries Olivia , Bonhomme Vincent , Brichant Jean-François , Rosanova Mario , Raz Aeyal , Tononi Giulio , Massimini Marcello , Laureys Steven , Boly Mélanie 
Published: November 2017

AbstractBackgroundImpaired consciousness has been associated with impaired cortical signal propagation following transcranial magnetic stimulation (TMS). Herein we hypothesized that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy.MethodsEight subjects underwent left occipital TMS coupled with high-density electroencephalograph (EEG) recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of evoked and induced source-space responses was used to investigate propofol’s effects on connectivity between regions.ResultsPropofol produced a wideband reduction in evoked power following TMS in five out of six electrodes. Bayesian Model Selection supported a DCM with hierarchical feedforward and feedback connections to best fit the data. DCM of induced responses revealed that the primary effect of propofol was impaired feedforward responses in cross frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, Family Wise Error corrected p<0.05). An exploratory analysis (thresholded at uncorrected p<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Posthoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left sided occipital and parietal cortex (T contrast p=0.004, Bonferroni corrected).ConclusionsOur data suggest that propofol-induced loss of consciousness is associated with reduced evoked power and impaired hierarchical feedforward connectivity following occipital TMS.
A multi-center study on factors influencing the reproducibility ofin vitrodrug-response studies
Authors: Niepel Mario , Hafner Marc , Mills Caitlin E. , Subramanian Kartik , Williams Elizabeth H. , Chung Mirra , Gaudio Benjamin , Barrette Anne Marie , Stern Alan D. , Hu Bin , Korkola James E. ,   LINCS Consortium, Gray Joe W. , Birtwistle Marc R. , Heiser Laura M. , Sorger Peter K. 
Published: November 2017

SUMMARYEvidence that some influential biomedical results cannot be repeated has increased interest in practices that generate data meeting findable, accessible, interoperable and reproducible (FAIR) standards. Multiple papers have identified examples of irreproducibility, but practical steps for increasing reproducibility have not been widely studied. Here, seven research centers in the NIH LINCS Program Consortium investigate the reproducibility of a prototypical perturbational assay: quantifying the responsiveness of cultured cells to anti-cancer drugs. Such assays are important for drug development, studying cell biology, and patient stratification. While many experimental and computational factors have an impact on intra- and inter-center reproducibility, the factors most difficult to identify and correct are those with a strong dependency on biological context. These factors often vary in magnitude with the drug being analyzed and with growth conditions. We provide ways of identifying such context-sensitive factors, thereby advancing the conceptual and practical basis for greater experimental reproducibility.
Adapting machine-learning algorithms to design gene circuits
Authors: Hiscock Tom 
Published: November 2017

AbstractBiological systems rely on complex networks, such as transcriptional circuits and protein-protein interaction networks, to perform a variety of functions e.g. responding to stimuli, directing cell fate, or patterning an embryo. Mathematical models are often used to ask: given some network, what function does it perform? However, we often want precisely the opposite i.e. given some circuit – either observedin vivo, or desired for some engineering objective – what biological networks could execute this function? Here, we adapt optimization algorithms from machine learning to rapidly screen and design gene circuits capable of performing arbitrary functions. We demonstrate the power of this approach by designing circuits (1) that recapitulate importantin vivophenomena, such as oscillators, and (2) to perform complex tasks for synthetic biology, such as counting noisy biological events. Our method can be readily applied to biological networks of any type and size, and is provided as an open-source and easy-to-use python module, GeneNet.
Degradation of cyclin B is critical for nuclear division inTrypanosoma brucei
Authors: Hayashi Hanako , Akiyoshi Bungo 
Published: November 2017

AbstractKinetoplastids have a nucleus that contains the nuclear genome and a kinetoplast that contains the mitochondrial genome. These single-copy organelles must be duplicated and segregated faithfully to daughter cells at each cell division. InTrypanosoma brucei, although duplication of both organelles starts around the same time, segregation of the kinetoplast precedes that of the nucleus. Cytokinesis subsequently takes place so that daughter cells inherit a single copy of each organelle. Very little is known about the molecular mechanism that governs the timing of these events. Furthermore, it is thought thatT. bruceilacks a spindle checkpoint that delays the onset of nuclear division in response to spindle damage. Here we show that a mitotic cyclin CYC6 has a dynamic localization pattern during the cell cycle, including kinetochore localization from G2 to metaphase. Using CYC6 as a molecular cell cycle marker, we confirmed thatT. bruceicannot delay the onset of anaphase in response to a bipolar spindle assembly defect. Interestingly, expression of a stabilized form of CYC6 caused the nucleus to arrest in a metaphase-like state without preventing cytokinesis. We propose that trypanosomes have an ability to regulate the timing of nuclear division by modulating the CYC6 protein level, without a spindle checkpoint.
Prediction Error and Repetition Suppression Have Distinct Effects on Neural Representations of Visual Information
Authors: Tang Matthew F. , Smout Cooper A. , Arabzadeh Ehsan , Mattingley Jason B. 
Published: November 2017

AbstractPredictive coding theories argue that recent experience establishes expectations in the brain that generate prediction errors when violated. Prediction errors provide a possible explanation for repetition suppression, where evoked neural activity is attenuated across repeated presentations of the same stimulus. The predictive coding account argues repetition suppression arises because repeated stimuli are expected, whereas non-repeated stimuli are unexpected and thus elicit larger neural responses. Here we employed electroencephalography in humans to test the predictive coding account of repetition suppression by presenting sequences of visual gratings with orientations that were expected either to repeat or change in separate blocks of trials. We applied multivariate forward modelling to determine how orientation selectivity was affected by repetition and prediction. Unexpected stimuli were associated with significantly enhanced orientation selectivity, whereas selectivity was unaffected for repeated stimuli. Our results suggest that repetition suppression and expectation have separable effects on neural representations of visual feature information.