bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of technology‐enhanced learning in Endodontic education: a systematic review and meta‐analysis
Authors: Nagendrababu V. , Pulikkotil S. J. , Sultan O. S. , Jayaraman J. , Soh J. A. , Dummer P. M. H. 
Published: August 2018

AbstractThe aim of the present systematic review was to evaluate the effectiveness of technology‐enhanced learning (TEL) in the field of Endodontics to improve educational outcomes compared to traditional learning methods. Randomized controlled studies published in English were identified from two electronic databases (PubMed and Scopus) up to May 2018. Two authors independently performed study selection, data extraction and assessed the risk of bias (ROB). Any teaching method using TEL was considered as the intervention, and this was compared to traditional methods. The outcome measuring the effectiveness of learning activities was evaluated by Kirkpatrick's four‐level training evaluation model. The four levels of training outcomes are as follows: Reaction, Learning, Behaviour and Results. A meta‐analysis was performed to estimate the standardized mean difference (SMD) by the random effects model. In total, 13 studies were included in the systematic review. Only three studies were assessed as ‘low’ ROB. A meta‐analysis could not be performed in the domains of Reaction and Behaviour. No significant difference was observed in knowledge gain (Learning domain) between TEL and traditional methods (SMD, 0.14 (95% CI −0.10 to 0.39) I2 = 62.7%). Similarly, no difference was observed in performance (Behaviour domain). A variable response was found in attitude (Reaction domain). From the available evidence, it can be concluded that TEL is equally as effective as traditional learning methods.
Evidence for changing nerve growth factor signalling mechanisms during development, maturation and ageing in the rat molar pulp
Authors: Mahdee A. , Eastham J. , Whitworth J. M. , Gillespie J. I. 
Published: August 2018

AbstractAimTo examine rat molar pulp innervation and identify complex cellular signalling systems involving nerve growth factor (NGF) and its p75 receptors (NGFR) at different stages of development, maturation and ageing.MethodologyDecalcified mandibular first molar mesial cusps from Wistar rats of ages 0 day; 1, 2, 3, 4, 6, 9, 12 and 24 weeks (n = 5 per group) were sectioned (10 μm) and incubated with antibodies for NGF, NGFR, calcitonin gene‐related peptide (CGRP) and neurofilament. Nerve densities in worn and intact regions of 3‐ to 24‐week‐old rats were compared by anova, Bonferroni and t‐tests.ResultsDuring odontogenesis, differences in NGF and NGFR expression were observed, with no evidence of nerve fibres, suggesting a signalling mechanism controlling cellular differentiation and dentine formation. Tooth wear in 4‐week rats was associated with reduced NGF expression and significantly decreased CGRP axons within affected odontoblast regions. The underlying subodontoblasts started expressing NGF which continued until 9 weeks. This may promote a significant increase in CGRP nerve density in affected regions. Nerve density in intact odontoblast regions increased gradually and reached significant levels in 12‐week rats. Reduction in nerve densities within worn and intact regions of cusps was observed at 24 weeks.ConclusionsAge‐related changes and responses to tooth wear may be controlled by the NGF signalling mechanism, with roles in odontoblast/subodontoblast communication and control of sensory innervation at different stages of tooth development, maturation and ageing. Greater understanding of cellular and nerve regulation in the injured pulp may promote therapeutic strategies for pulp survival.
Prevalence, risk factors, and mortality outcome in the drug reaction with eosinophilia and systemic symptoms patients with cardiac involvement
Authors: Intarasupht Julphat , Kanchanomai Anchisa , Leelasattakul Wuttirak , Chantrarat Thoranis , Nakakes Artit , Tiyanon Waraporn 
Published: August 2018

AbstractBackgroundDrug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous drug reaction that can affect multiple internal organ systems. Cardiac involvement in DRESS syndrome (CiDs) is uncommon but can be life‐threatening.ObjectiveTo determine the prevalence, risk factors, and mortality outcome of CiDs.Material and methodsForty‐one patients who were diagnosed with probable and definite DRESS syndrome according to the RegiSCAR criteria were recruited. Cardiac involvement was evaluated by two independent cardiologists.ResultsThe cardiac involvement was found in 8/41 (19.5%) patients. Specifically, myocardial involvement was found in five patients, while three patients had pericardial involvement. The majority of culprit drugs were antibiotics followed by anti‐epileptic medications. The hemoglobin and albumin levels were significantly lower in the patients with CiDs when compared to the patients without CiDs (P‐value = 0.005 for both factors). The mortality rate at 30 and 90 days was significantly higher among CiDs patients, that is, 3/8 (37.5%) versus 2/28 (6.1%); P‐value = 0.02 and 4/8 (50.0%) versus 2/33 (6.1%); P‐value = 0.002 respectively.ConclusionOur study showed the prevalence of CiDs was as high as 19.5% with high mortality rate. We suggest a thorough cardiac evaluation in all DRESS patients with RegiSCAR score ≥4. The patients with CiDs had significantly lower hemoglobin and albumin levels, which might imply poor health condition, when compared to those without CiDs.
Dynamic balance of pro‐ and anti‐inflammatory signals controls disease and limits pathology
Authors: Cicchese Joseph M. , Evans Stephanie , Hult Caitlin , Joslyn Louis R. , Wessler Timothy , Millar Jess A. , Marino Simeone , Cilfone Nicholas A. , Mattila Joshua T. , Linderman Jennifer J. , Kirschner Denise E. 
Published: August 2018

AbstractImmune responses to pathogens are complex and not well understood in many diseases, and this is especially true for infections by persistent pathogens. One mechanism that allows for long‐term control of infection while also preventing an over‐zealous inflammatory response from causing extensive tissue damage is for the immune system to balance pro‐ and anti‐inflammatory cells and signals. This balance is dynamic and the immune system responds to cues from both host and pathogen, maintaining a steady state across multiple scales through continuous feedback. Identifying the signals, cells, cytokines, and other immune response factors that mediate this balance over time has been difficult using traditional research strategies. Computational modeling studies based on data from traditional systems can identify how this balance contributes to immunity. Here we provide evidence from both experimental and mathematical/computational studies to support the concept of a dynamic balance operating during persistent and other infection scenarios. We focus mainly on tuberculosis, currently the leading cause of death due to infectious disease in the world, and also provide evidence for other infections. A better understanding of the dynamically balanced immune response can help shape treatment strategies that utilize both drugs and host‐directed therapies.
Herpes simplex virus‐2 dynamics as a probe to measure the extremely rapid and spatially localized tissue‐resident T‐cell response
Authors: Schiffer Joshua T. , Swan David A. , Prlic Martin , Lund Jennifer M. 
Published: August 2018

SummaryHerpes simplex virus‐2 infection is characterized by frequent episodic shedding in the genital tract. Expansion in HSV‐2 viral load early during episodes is extremely rapid. However, the virus invariably peaks within 18 hours and is eliminated nearly as quickly. A critical feature of HSV‐2 shedding episodes is their heterogeneity. Some episodes peak at 108 HSV DNA copies, last for weeks due to frequent viral re‐expansion, and lead to painful ulcers, while others only reach 103 HSV DNA copies and are eliminated within hours and without symptoms. Within single micro‐environments of infection, tissue‐resident CD8+ T cells (TRM) appear to contain infection within a few days. Here, we review components of TRM biology relevant to immune surveillance between HSV‐2 shedding episodes and containment of infection upon detection of HSV‐2 cognate antigen. We then describe the use of mathematical models to correlate large spatial gradients in TRM density with the heterogeneity of observed shedding within a single person. We describe how models have been leveraged for clinical trial simulation, as well as future plans to model the interactions of multiple cellular subtypes within mucosa, predict the mechanism of action of therapeutic vaccines, and describe the dynamics of 3‐dimensional infection environment during the natural evolution of an HSV‐2 lesion.
Modeling the dynamics of hepatitis B infection, immunity, and drug therapy
Authors: Ciupe Stanca M 
Published: August 2018

SummaryHepatitis B virus infection is the cause of liver diseases such as cirrhosis and liver cancer. Understanding the host‐virus mechanisms that mediate virus pathogenesis can help design better preventive measures for disease control. Mathematical models have been used alongside experimental data to provide insight into the role of immune responses during the acute and chronic hepatitis B infections as well as virus dynamics following administration of combined drug therapy. In this paper, we review several modeling studies on virus‐host interactions during acute infection, the virus‐host characteristics responsible for transition to chronic disease, and the efficacy and optimal control measures of drug therapy. We conclude by presenting our opinion on the future directions of the field.
Mathematical modeling of within‐host Zika virus dynamics
Authors: Best Katharine , Perelson Alan S 
Published: August 2018

SummaryRecent Zika virus outbreaks have been associated with severe outcomes, especially during pregnancy. A great deal of effort has been put toward understanding this virus, particularly the immune mechanisms responsible for rapid viral control in the majority of infections. Identifying and understanding the key mechanisms of immune control will provide the foundation for the development of effective vaccines and antiviral therapy. Here, we outline a mathematical modeling approach for analyzing the within‐host dynamics of Zika virus, and we describe how these models can be used to understand key aspects of the viral life cycle and to predict antiviral efficacy.
Virus dynamics and phyloanatomy: Merging population dynamic and phylogenetic approaches
Authors: Bons Eva , Regoes Roland R 
Published: August 2018

SummaryIn evolutionary biology and epidemiology, phylodynamic methods are widely used to infer population biological characteristics, such as the rates of replication, death, migration, or, in the epidemiological context, pathogen spread. More recently, these methods have been used to elucidate the dynamics of viruses within their hosts. Especially the application of phylogeographic approaches has the potential to shed light on anatomical colonization pathways and the exchange of viruses between distinct anatomical compartments. We and others have termed this phyloanatomy. Here, we review the promise and challenges of phyloanatomy, and compare them to more classical virus dynamics and population genetic approaches. We argue that the extremely strong selection pressures that exist within the host may represent the main obstacle to reliable phyloanatomic analysis.
Interferon at the cellular, individual, and population level in hepatitis C virus infection: Its role in the interferon‐free treatment era
Authors: Raja Rubesh , Baral Subhasish , Dixit Narendra M. 
Published: August 2018

SummaryThe advent of powerful direct‐acting antiviral agents (DAAs) has revolutionized the treatment of hepatitis C. DAAs cure nearly all patients with short duration, oral treatments. Significant efforts are now underway to optimize DAA‐based treatments. We discuss the potential role of interferon in this optimization. Clinical studies present compelling evidence that DAAs perform better in treatment‐naive individuals than in individuals who previously failed treatment with interferon, a surprising correlation because interferon and DAAs are thought to act independently. Recent mathematical models explore a mechanistic hypothesis underlying this correlation. The hypothesis invokes the action of interferon at the cellular, individual, and population levels. Strong interferon responses prevent the productive infection of cells, reduce viral replication, and impede the development of resistance to DAAs in infected individuals and improve cure rates elicited by DAAs in treated populations. The models develop descriptions of these processes, integrate them into a comprehensive framework, and capture clinical data quantitatively, providing a successful test of the hypothesis. Individuals with strong endogenous interferon responses thus present a promising subpopulation for reducing DAA treatment durations. This review discusses the conceptual advances made by the models, highlights the new insights they unravel, and examines their applicability to optimize DAA‐based treatments.
Molecular mechanisms of T cell sensitivity to antigen
Authors: Siller‐Farfán Jesús A. , Dushek Omer 
Published: August 2018

AbstractT cells initiate and regulate adaptive immune responses that can clear infections. To do this, they use their T cell receptors (TCRs) to continually scan the surfaces of other cells for cognate peptide antigens presented on major histocompatibility complexes (pMHCs). Experimental work has established that as few 1‐10 pMHCs are sufficient to activate T cells. This sensitivity is remarkable in light of a number of factors, including the observation that the TCR and pMHC are short molecules relative to highly abundant long surface molecules, such as CD45, that can hinder initial binding, and moreover, the TCR/pMHC interaction is of weak affinity with solution lifetimes of approximately 1 second. Here, we review experimental and mathematical work that has contributed to uncovering molecular mechanisms of T cell sensitivity. We organize the mechanisms by where they act in the pathway to activate T cells, namely mechanisms that (a) promote TCR/pMHC binding, (b) induce rapid TCR signaling, and (c) amplify TCR signaling. We discuss work showing that high sensitivity reduces antigen specificity unless molecular feedbacks are invoked. We conclude by summarizing a number of open questions.
Host‐pathogen kinetics during influenza infection and coinfection: insights from predictive modeling
Authors: Smith Amber M 
Published: August 2018

SummaryInfluenza virus infections are a leading cause of morbidity and mortality worldwide. This is due in part to the continual emergence of new viral variants and to synergistic interactions with other viruses and bacteria. There is a lack of understanding about how host responses work to control the infection and how other pathogens capitalize on the altered immune state. The complexity of multi‐pathogen infections makes dissecting contributing mechanisms, which may be non‐linear and occur on different time scales, challenging. Fortunately, mathematical models have been able to uncover infection control mechanisms, establish regulatory feedbacks, connect mechanisms across time scales, and determine the processes that dictate different disease outcomes. These models have tested existing hypotheses and generated new hypotheses, some of which have been subsequently tested and validated in the laboratory. They have been particularly a key in studying influenza‐bacteria coinfections and will be undoubtedly be useful in examining the interplay between influenza virus and other viruses. Here, I review recent advances in modeling influenza‐related infections, the novel biological insight that has been gained through modeling, the importance of model‐driven experimental design, and future directions of the field.
Current best estimates for the average lifespans of mouse and human leukocytes: reviewing two decades of deuterium‐labeling experiments
Authors: Borghans José A. M. , Tesselaar Kiki , de Boer Rob J. 
Published: August 2018

SummaryDeuterium is a non‐toxic, stable isotope that can safely be administered to humans and mice to study their cellular turnover rates in vivo. It is incorporated into newly synthesized DNA strands during cell division, without interference with the kinetics of cells, and the accumulation and loss of deuterium in the DNA of sorted (sub‐)populations of leukocytes can be used to estimate their cellular production rates and lifespans. In the past two decades, this powerful technology has been used to estimate the turnover rates of various types of leukocytes. Although it is the most reliable technique currently available to study leukocyte turnover, there are remarkable differences between the cellular turnover rates estimated by some of these studies. We have recently established that part of this variation is due to (a) difficulties in estimating deuterium availability in some deuterium‐labeling studies, and (b) assumptions made by the mathematical models employed to fit the data. Being aware of these two problems, we here aim to approach a consensus on the life expectancies of different types of T cells, B cells, monocytes, and neutrophils in mice and men. We address remaining outstanding problems whenever appropriate and discuss for which immune subpopulations we currently have too little information to draw firm conclusions about their turnover.
The natural history of naive T cells from birth to maturity
Authors: Seddon Benedict , Yates Andrew J. 
Published: August 2018

SummaryGenerating and maintaining a diverse repertoire of naive T cells is essential for protection against pathogens, and developing a mechanistic and quantitative description of the processes involved lies at the heart of our understanding of vertebrate immunity. Here, we review the biology of naive T cells from birth to maturity and outline how the integration of mathematical models and experiments has helped us to develop a full picture of their life histories.
Some deterministic and stochastic mathematical models of naïve T‐cell homeostasis
Authors: Lythe Grant , Molina‐París Carmen 
Published: August 2018

AbstractHumans live for decades, whereas mice live for months. Over these long timescales, naïve T cells die or divide infrequently enough that it makes sense to approximate death and division as instantaneous events. The population of T cells in the body is naturally divided into clonotypes; a clonotype is the set of cells that have identical T‐cell receptors. While total numbers of cells, such as naïve CD4+ T cells, are large enough that ordinary differential equations are an appropriate starting point for mathematical models, the numbers of cells per clonotype are not. Here, we review a number of basic mathematical models of the maintenance of clonal diversity. As well as deterministic models, we discuss stochastic models that explicitly track the integer number of naïve T cells in many competing clonotypes over the lifetime of a mouse or human, including the effect of waning thymic production. Experimental evaluation of clonal diversity by bulk high‐throughput sequencing has many difficulties, but the use of single‐cell sequencing is restricted to numbers of cells many orders of magnitude smaller than the total number of T cells in the body. Mathematical questions associated with extrapolating from small samples are therefore key to advances in understanding the diversity of the repertoire of T cells. We conclude with some mathematical models on how to advance in this area.
Within‐host modeling of blood‐stage malaria
Authors: Khoury David S. , Aogo Rosemary , Randriafanomezantsoa‐Radohery Georges , McCaw James M. , Simpson Julie A. , McCarthy James S. , Haque Ashraful , Cromer Deborah , Davenport Miles P. 
Published: August 2018

SummaryMalaria infection continues to be a major health problem worldwide and drug resistance in the major human parasite species,Plasmodium falciparum, is increasing in South East Asia. Control measures including novel drugs and vaccines are in development, and contributions to the rational design and optimal usage of these interventions are urgently needed. Infection involves the complex interaction of parasite dynamics, host immunity, and drug effects. The long life cycle (48 hours in the common human species) and synchronized replication cycle of the parasite population present significant challenges to modeling the dynamics ofPlasmodiuminfection. Coupled with these, variation in immune recognition and drug action at different life cycle stages leads to further complexity. We review the development and progress of “within‐host” models ofPlasmodiuminfection, and how these have been applied to understanding and interpreting human infection and animal models of infection.
Antiviral interferon response at single‐cell resolution
Authors: Talemi Soheil Rastgou , Höfer Thomas 
Published: August 2018

SummaryExperimental studies of the innate immune response of mammalian cells to viruses reveal pervasive heterogeneity at the level of single cells. Interferons are induced only in a fraction of virus‐infected cells; subsequently a fraction of cells exposed to interferons upregulate interferon‐stimulated genes. Nevertheless, quantitative experiments and linked mathematical models show that the interferon response can be effective in curbing viral spread through two distinct mechanisms. First, paracrine interferon signals from scattered source cells can protect many uninfected cells, and the self‐amplification of interferon production might serve to calibrate response amplitude to strength of viral infection. Second, models of the tug‐of‐war between viral replication and the innate interferon response imply a pivotal role of interferon action on already infected cells in curbing viral spread, through effectively lowering virus replication rate. This finding is in line with the observation that several pathogenic viruses selectively abrogate interferon action on infected cells. Thus, interferons may delay viral spread in acute infections by acting as sentinels, warning uninfected cells of imminent danger, or as negative feedback regulators of virus replication in infected cells. The timing of the interferon response relative to the onset of viral replication is critical for its effectiveness in curbing viral spread.
Synthesis, structure, and dielectric properties of a new binary antiferroelectric solid solution: (1−x)Pb(Mg1/2W1/2)O3–xPbHfO3
Authors: Gao Pan , Liu Zenghui , Wu Hua , Ren Wei , Ye Zuo‐Guang 
Published: August 2018

AbstractDielectric ceramics are one of the most important electrical insulators because of their excellent electrical stability and nonconducting properties. In this work, new complex perovskite solid solutions, (1−x)Pb(Mg1/2W1/2)O3–xPbHfO3 [(1−x) PMW–xPHf] (0.00 ≤ x ≤ 0.04), were successfully synthesized in the form of ceramics by the solid‐state reaction method and sintering process. The X‐ray diffraction results indicate that a single perovskite phase with antiferroelectric (AFE) orthorhombic Pmcn symmetry is formed for x < 0.04 which corresponds to the PMW‐type solid solution (SS‐PMW). For the composition x = 0.04, however, a small amount (about 1%) of ferroelectric orthorhombic C2mm phase that arises from the PHf‐type solid solution (SS‐PHf) was found to coexist with the Pmcn phase (99%). The dielectric measurements show that the AFE‐paraelectric phase transition temperature TC of the (1−x)PMW–xPHf ceramics increases from 38.2°C (x = 0) to 40.1°C (x = 0.03) with the increasing PHf content, indicating a slightly enhanced AFE ordering degree. The studied materials show a relatively low dielectric constant (~102), a low dielectric loss (~10−2), a high breakdown field strength (~140 kV/cm), and a linear electric field dependence of polarization at room temperature, which make them a new candidate for potential applications as ceramic insulators.