bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparative Analysis of Recombinant Human Bone Morphogenetic Protein-2 with a Demineralized Bone Matrix versus Iliac Crest Bone Graft for Secondary Alveolar Bone Grafts in Patients with Cleft Lip and Palate: Review of 501 Cases
Authors: Hammoudeh Jeffrey A. , Fahradyan Artur , Gould Daniel J. , Liang Fan , Imahiyerobo Thomas , Urbinelli Leo , Nguyen JoAnna T. , Magee William , Yen Stephen , Urata Mark M. 
Published: April 2017

Background:
Alveolar cleft reconstruction using iliac crest bone graft is considered standard of care for children with complete cleft lip and palate at the time of mixed dentition. Harvesting bone may result in donor-site morbidity and additional operating time and length of hospitalization. Recombinant human bone morphogenetic protein (rhBMP)-2 with a demineralized bone matrix is an alternative bone source for alveolar cleft reconstruction. The authors investigated the outcomes of rhBMP-2/demineralized bone matrix versus iliac crest bone graft for alveolar cleft reconstruction by reviewing postoperative surgical complications and cleft closure.

Methods:
A retrospective chart review was conducted for 258 rhBMP-2/demineralized bone matrix procedures (mean follow-up, 2.9 years) and 243 iliac crest bone graft procedures (mean follow-up, 4.1 years) on 414 patients over a 12-year period. The authors compared complications, canine eruption, and alveolar cleft closure between the two groups.

Results:
In the rhBMP-2/demineralized bone matrix group, one patient required prolonged intubation because of intraoperative airway swelling not thought to be caused by rhBMP-2, 36 reported facial swelling and one required outpatient steroids as treatment, and 12 had dehiscence; however, half of these complications resolved without intervention. Twenty-three of the 228 rhBMP-2/demineralized bone matrix patients and 28 of the 242 iliac crest bone graft patients required repeated surgery for alveolar cleft repair. Findings for canine tooth eruption into the cleft site through the graft were similar between the groups.

Conclusions:
The rhBMP-2/demineralized bone matrix appears to be an acceptable alternative for alveolar cleft repair. The authors found no increase in serious adverse events with the use of this material. Local complications, such as swelling and minor wound dehiscence, predominantly improved without intervention.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Effects of a Laboratory Health Information Exchange Intervention on Antiretroviral Therapy Use, Viral Suppression, and Racial/Ethnic Disparities
Authors: Cunningham William E. , Ford Chandra L. , Kinsler Janni J. , Seiden Danielle , Andrews Laral , Nakazono Terry , Bell Douglas S. 
Published: April 2017

Background:
Although antiretroviral therapy (ART) is available to treat HIV+ persons and prevent transmission, ineffective delivery of care may delay ART use, impede viral suppression (VS), and contribute to racial/ethnic disparities along the continuum of care. This study tested the effects of a bi-directional laboratory health information exchange (LHIE) intervention on each of these outcomes.

Methods:
We used a quasi-experimental, interrupted time-series design to examine whether the LHIE intervention improved ART use and VS, and reduced racial/ethnic disparities in these outcomes among HIV+ patients (N = 1181) in a comprehensive HIV/AIDS clinic in Southern California. Main outcome measures were ART pharmacy fill and HIV viral load laboratory data extracted from the medical records over 3 years. Race/ethnicity and an indicator for the intervention (after vs. before) were the main predictors. The analysis involved 3-stage, multivariable logistic regression with generalized estimating equations.

Results:
Overall, the intervention predicted greater odds of ART use (odds ratio [OR] = 2.50; 95% confidence interval: 2.29 to 2.73; P < 0.001) and VS (OR = 1.12; 95% confidence interval: 1.04 to 1.21; P < 0.05) in the final models that included sociodemographic, behavioral, and clinical covariates. Before the intervention, there were significant black/white disparities in ART use OR = 0.75 (0.58–0.98; P = 0.04) and VS OR = 0.75 (0.61–0.92; P = 0.001). After the intervention, the black/white disparities decreased after adjusting for sociodemographics and the number of HIV care visits, and Latinos had greater odds than whites of ART use and VS, adjusting for covariates.

Conclusions:
The intervention improved overall ART treatment and VS, and reduced black/white disparities. LHIE interventions may hold promise if implemented among similar patients.
Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents
Authors: Runge Val M. 
Published: April 2017

Abstract
For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents—specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)—for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.
Genetic Ancestry and Susceptibility to Late-Onset Alzheimer Disease (LOAD) in the Admixed Colombian Population
Authors: Moreno Diana J. , Pino Sebastián , Ríos Ángela , Lopera Francisco , Ostos Henry , Via Marc , Bedoya Gabriel 
Published: April 2017

Introduction:
Differences in the prevalence of dementia among populations and in the effect of apolipoprotein E (APOE) on the emergence of Alzheimer disease (AD), which is the main type of dementia, have been reported.

Methods:
This study estimated the ancestry of a group of individuals with late-onset Alzheimer disease (LOAD) (N=280) and established whether there were any differences when compared with a control group (N=357) in a sample of the Colombian population.

Results:
When the analyses were adjusted for known risk factors such as age, sex, presence of APOEɛ4, socioeconomic status, educational attainment, and place of birth, African ancestry was associated with an increased LOAD risk (odds ratio: 1.55; 95% confidence interval, 1.09-2.03; P=0.029), whereas Native American ancestry was associated with lower risk (odds ratio: 0.75; 95% confidence interval, 0.61-0.98; P=0.046), for every 10% increase in ancestry. In addition, there were significant differences in the proportion of Native American ancestry between carriers and noncarriers of the APOEɛ4 allele (Mann-Whitney U test, P=0.047), with noncarriers having higher mean Native American ancestry when compared with carriers.

Conclusions:
Our results are consistent with the presence of variants of African origin in the genome of the Colombian population and different from APOEɛ4 that represents a risk factor for the development of LOAD, whereas variants of Native American origin may be conferring protection. However, unknown environmental factors or epigenetic differences among continental groups could also explain the observed associations.
Immunomodulation for glioblastoma
Authors: Reardon David A. , Wen Patrick Y. , Wucherpfennig Kai W. , Sampson John H. 
Published: April 2017

Purpose of review
Immunotherapy has emerged as a cornerstone of modern oncology with regulatory approvals for a variety of immunotherapeutics being achieved for a spectrum of cancer indications. Nonetheless the role of these approaches for patients with glioblastoma (GBM), the most common and deadliest primary malignant brain neoplasm, remains unknown. In this review, we summarize the current status of clinical development for the major types of immunotherapeutics, including vaccines, cell-based therapies, and immune checkpoint modulators for GBM. We also highlight potential challenges confronting the development of these agents.

Recent findings
Growing preclinical and clinical data is emerging regarding the potential of immunotherapy strategies for GBM. In parallel, growing data demonstrating that historical dogma classifying the brain as immunoprivileged is inaccurate but that many tumors, including GBM evoke myriad mechanisms to suppress antitumor immune responses.

Summary
Ongoing initial trials will provide preliminary data on the role of immunotherapy for GBM patients. Subsequent clinical development steps will likely require rationally designed combinatorial regimens.
Rayleigh–Taylor instability in soft elastic layers
Authors: Riccobelli D. , Ciarletta P. 
Published: April 2017

This work investigates the morphological stability of a soft body composed of two heavy elastic layers attached to a rigid surface and subjected only to the bulk gravity force. Using theoretical and computational tools, we characterize the selection of different patterns as well as their nonlinear evolution, unveiling the interplay between elastic and geometric effects for their formation. Unlike similar gravity-induced shape transitions in fluids, such as the Rayleigh–Taylor instability, we prove that the nonlinear elastic effects saturate the dynamic instability of the bifurcated solutions, displaying a rich morphological diagram where both digitations and stable wrinkling can emerge. The results of this work provide important guidelines for the design of novel soft systems with tunable shapes, with several applications in engineering sciences.
This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’
Development of amplicon deep sequencing markers and data analysis pipeline for genotyping multi-clonal malaria infections
Authors: Lerch Anita , Koepfli Cristian , Hofmann Natalie , Messerli Camilla , Wilcox Stephen , Kattenberg Johanna H. , Betuela Inoni , O’Connor Liam , Mueller Ivo , Felger Ingrid 
Published: April 2017

AbstractAmplicon deep sequencing permits sensitive detection of minority clones and improves discriminatory power for genotyping multi-clonePlasmodium falciparuminfections. Such high resolution is needed for molecular monitoring of drug efficacy trials. Targeted sequencing of molecular markercspand novel markercpmpwas conducted in duplicate on mixtures of parasite culture strains and 37 field samples. A protocol to multiplex up to 384 samples in a single sequencing run was applied. Software “HaplotypR” was developed for data analysis.Cpmpwas highly diverse (He=0.96) in contrast tocsp(He=0.57). Minority clones were robustly detected if their frequency was >1%. False haplotype calls owing to sequencing errors were observed below that threshold. To reliably detect haplotypes at very low frequencies, experiments are best performed in duplicate and should aim for coverage of >10’000 reads/amplicon. When compared to length polymorphic markermsp2, highly multiplexed amplicon sequencing displayed greater sensitivity in detecting minority clones.
A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis
Authors: Mishra Ajay , Pisco Angela Oliveira , Oules Benedicte , Ly Tony , Liakath-Ali Kifayathullah , Walko Gernot , Viswanathan Priyalakshmi , Nijjhar Jagdeesh , Dunn Sara-Jane , Lamond Angus I. , Watt Fiona M. 
Published: April 2017

AbstractEpidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation1,2. While progress has been made in characterising the stem and differentiated cell compartments3, the transition between the two cell states, termed commitment4, is poorly understood. Here we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension for up to 12h. We have previously shown that commitment begins at approximately 4h and differentiation is initiated by 8h5. We find that cell detachment induces a network of protein phosphatases. The pro-commitment phosphatases – including DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA – promote terminal differentiation by negatively regulating ERK MAPK and positively regulating key API transcription factors. Their activity is antagonised by concomitant upregulation of the anti-commitment phosphatase DUSP10. The phosphatases form a dynamic network of transient positive and negative interactions, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem cell and differentiated cell) via an unstable (committed) state. In addition phosphatase expression is spatially regulated relative to the location of stem cells, both in vivo and in response to topographical cues in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.
Gamma and beta bursts during working memory read-out suggest roles in its volitional control
Authors: Lundqvist Mikael , Herman Pawel , Warden Melissa R. , Brincat Scott L. , Miller Earl K. 
Published: April 2017

AbstractWorking memory (WM) activity is not as stationary or sustained as previously thought. There are brief bursts of gamma (∼55–120 Hz) and beta (∼20–35 Hz) oscillations, the former linked to stimulus information in spiking. We examine these dynamics in relation to read-out from WM, which is still not well understood. Monkeys held a sequence of two objects and had to decide if they matched a subsequent sequence. Changes in the balance of beta/gamma suggested their role in WM control. In anticipation of having to use an object for the match decision, there was an increase in spiking information about that object along with an increase in gamma and a decrease in beta. When an object was no longer needed, beta increased and gamma as well as spiking information about that object decreased. Deviations from these dynamics predicted behavioral errors. Thus, turning up or down beta could regulate gamma and the information in working memory.
Quantitative agent-based modeling reveals mechanical stress response of growing tumor spheroids is predictable over various growth conditions and cell lines
Authors: Liedekerke Paul Van , Neitsch Johannes , Johann Tim , Alessandri Kevin , Nassoy Pierre , Drasdo Dirk 
Published: April 2017

AbstractModel simulations indicate that the response of growing cell populations on mechanical stress follows the same functional relationship and is predictable over different cell lines and growth conditions despite the response curves look largely different. We develop a hybrid model strategy in which cells are represented by coarse-grained individual units calibrated with a high resolution cell model and parameterized measurable biophysical and cell-biological parameters. Cell cycle progression in our model is controlled by volumetric strain, the latter being derived from a bio-mechanical relation between applied pressure and cell compressibility. After parameter calibration from experiments with mouse colon carcinoma cells growing against the resistance of an elastic alginate capsule, the model adequately predicts the growth curve in i) soft and rigid capsules, ii) in different experimental conditions where the mechanical stress is generated by osmosis via a high molecular weight dextran solution, and iii) for other cell types with varying doubling times. Our model simulation results suggest that the growth response of cell population upon externally applied mechanical stress is the same, as it can be quantitatively predicted using the same growth progression function.Author summaryThe effect of mechanical resistance on the growth of tumor cells remains today largely unquantified. We studied data from two different experimental setups that monitor the growth of tumor cells under mechanical compression. The existing data in the first experiment examined growing CT26 cells in an elastic permeable capsule. In the second experiment, growth of tumor cells under osmotic stress of the same cell line as well as other cell lines were studied. We have developed and agent-based model with measurable biophysical and cell-biological parameters that can simulate both experiments. Cell cycle progression in our model is a Hill function of cell volumetric strain, derived from a bio-mechanical relation between applied pressure and cell compressibility. After calibration of the model parameters within the data of the first experiment, we are able predict the growth rates in the second experiment. We show that that the growth response of cell populations upon externally applied mechanical stress in the two different experiments and over different cell lines can be predicted using the same growth progression function once the growth kinetics of the cell lines in abscence of mechanical stress is known.
Multiplex genome editing by natural transformation (MuGENT) for synthetic biology inVibrio natriegens
Authors: Dalia Triana N. , Hayes Chelsea A. , Stolyar Sergey , Marx Christopher J. , McKinlay James B. , Dalia Ankur B. 
Published: April 2017

ABSTRACTVibrio natriegenshas recently emerged as an alternative toEscherichia colifor molecular biology and biotechnology, but low-efficiency genetic tools hamper its development. Here, we uncover how to induce natural competence inV. natriegensand describe methods for multiplex genome editing by natural transformation (MuGENT). MuGENT promotes integration of multiple genome edits at high-efficiency on unprecedented timescales. Also, this method allows for generating highly complex mutant populations, which can be exploited for metabolic engineering efforts. As a proof-of-concept, we attempted to enhance production of the value added chemical poly-β-hydroxybutyrate (PHB) inV. natriegensby targeting the expression of nine genes involved in PHB biosynthesis via MuGENT. Within 1 week, we isolated edited strains that produced ~100 times more PHB than the parent isolate and ~3.3 times more than a rationally designed strain. Thus, the methods described here should extend the utility of this species for diverse academic and industrial applications.
Memory and Perception-based Facial Image Reconstruction
Authors: Chang Chi-Hsun , Nemrodov Dan , Lee Andy C. H. , Nestor Adrian 
Published: April 2017

AbstractVisual memory for faces has been extensively researched, especially regarding the main factors that influence face memorability. However, what we remember exactly about a face, namely, the pictorial content of visual memory, remains largely unclear. The current work aims to elucidate this issue by reconstructing face images from both perceptual and memory-based behavioural data. Specifically, our work builds upon and further validates the hypothesis that visual memory and perception share a common representational basis underlying facial identity recognition. To this end, we derived facial features directly from perceptual data and then used such features for image reconstruction separately from perception and memory data. Successful levels of reconstruction were achieved in both cases for newly-learned faces as well as for familiar faces retrieved from long-term memory. Theoretically, this work provides insights into the content of memory-based representations while, practically, it opens the path to novel applications, such as computer-based ‘sketch artists’.