bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of single‐dose ceftaroline fosamil in children with cystic fibrosis
Authors: Le Jennifer , Bradley John S. , Hingtgen Sara , Skochko Shannon , Black Nanette , Jones Ronald N. , Lim Meerana , Capparelli Edmund V. 
Published: September 2017

AbstractBackgroundSingle‐dose pharmacokinetics (PK) and safety of ceftaroline fosamil with population pharmacokinetic/pharmacodynamic (PK/PD) modeling for staphylococcal pneumonia was performed in children with CF.MethodsSubjects between 6 and 18 years old were evaluated in this phase 1, open‐label, single‐dose, prospective study using 10 mg/kg (up to 600 mg). Non‐compartmental analysis and population‐based PK analyses with Monte Carlo simulation (for doses 8‐20 mg/kg every 8 h, infused over 1‐4 h) were conducted.ResultsA total of 20 subjects were enrolled. The median age and weight were 12 yr (range 6.3‐17.4) and 38.7 kg (range 17.8‐94.3), respectively. A 3‐compartment linear model incorporating age and weight provided the best fit for the data. Comparing children 6 to <12 years to those 12 to <18 years, the mean posthoc Bayesian parameter estimates for total volume of distribution (VT) were 0.32 ± 0.05 L/kg versus 0.32 ± 0.04 L/kg, P = 0.7; and total Clearance (CLT), 0.50 ± 0.10 L/h/kg versus 0.30 ± 0.07 L/h/kg, P = 0.001. Using susceptibility data from pediatric MRSA lower respiratory tract isolates, 8 mg/kg (maximum of 1000 mg per dose) infused over 1 h every 8 h achieved free‐drug plasma concentrations above the minimum inhibitory concentration for ≥60% of the dosing interval in at least 95% of virtual subjects.ConclusionsSince children with CF have increased ceftaroline CL compared with published data from non‐CF children; greater dosages may be required in children with CF to achieve adequate exposure in the treatment of MRSA pneumonia. Pharmacodynamic‐based dosing predicts that dosing should also be based on the patient's MRSA MIC.
Modeling CAPRI targets 110‐120 by template‐based and free docking using contact potential and combined scoring function
Authors: Kundrotas Petras J. , Anishchenko Ivan , Badal Varsha D. , Das Madhurima , Dauzhenka Taras , Vakser Ilya A. 
Published: September 2017

AbstractThe paper presents analysis of our template‐based and free docking predictions in the joint CASP12/CAPRI37 round. A new scoring function for template‐based docking was developed, benchmarked on the Dockground resource, and applied to the targets. The results showed that the function successfully discriminates the incorrect docking predictions. In correctly predicted targets, the scoring function was complemented by other considerations, such as consistency of the oligomeric states among templates, similarity of the biological functions, biological interface relevance, etc. The scoring function still does not distinguish well biological from crystal packing interfaces, and needs further development for the docking of bundles of α‐helices. In the case of the trimeric targets, sequence‐based methods did not find common templates, despite similarity of the structures, suggesting complementary use of structure‐ and sequence‐based alignments in comparative docking. The results showed that if a good docking template is found, an accurate model of the interface can be built even from largely inaccurate models of individual subunits. Free docking however is very sensitive to the quality of the individual models. However, our newly developed contact potential detected approximate locations of the binding sites.
Misunderstanding the preorganization concept can lead to confusions about the origin of enzyme catalysis
Authors: Jindal Garima , Warshel Arieh 
Published: September 2017

AbstractUnderstanding the origin of the catalytic power of enzymes has both conceptual and practical importance. One of the most important finding from computational studies of enzyme catalysis is that a major part of the catalytic power is due to the preorganization of the enzyme active site. Unfortunately, misunderstanding of the nontrivial preorganization idea lead some to assume that it does not consider the effect of the protein residues. This major confusion reflects a misunderstanding of the statement that the interaction energy of the enzyme group and the transition state (TS) is similar to the corresponding interaction between the water molecules (in the reference system) and the TS, and that the catalysis is due to the reorganization free energy of the water molecules. Obviously, this finding does not mean that we do not consider the enzyme groups. Another problem is the idea that catalysis is due to substrate preorganization. This more traditional idea is based in some cases on inconsistent interpretation of the action of model compounds, which unfortunately, do not reflect the actual situation in the enzyme active site. The present article addresses the above problems, clarifying first the enzyme polar preorganization idea and the current misunderstandings. Next we take a specific model compound that was used to promote the substrate preorganization proposal and establish its irrelevance to enzyme catalysis. Overall, we show that the origin of the catalytic power of enzymes cannot be assessed uniquely without computer simulations, since at present this is the only way of relating structure and energetics.
The Use of Traditional Herbal Medicines Amongst South Asian Diasporic Communities in the UK
Authors: Bhamra Sukvinder K. , Slater Adrian , Howard Caroline , Johnson Mark , Heinrich Michael 
Published: September 2017

Migrant South Asian communities in the UK have brought with them their own traditional forms of medicine, yet little is known about their current use of herbal medicines (HMs) in the UK. The aim of the study was to explore the origins, use and transmission of knowledge of traditional HMs used by diasporic South Asian communities in the UK. A researcher‐administered questionnaire was used for data collection (n = 192). An opportunity sampling technique was used to recruit participants across several locations in Birmingham and Leicester. Two thirds of participants (n = 126) stated they used HMs to maintain their health and to treat various health conditions such as digestive problems, skin conditions and diabetes. Almost 2000 actively used HMs were documented including 123 plant species that were identified. Participants imported HMs from abroad as well as sourcing them locally and even growing some of their own plants. Up to 82% (n = 87) of participants who took prescription medicines did not tell their healthcare professionals about any HMs they consumed; this raises concerns about people's knowledge of herb–drug interactions, compliance and effect on prescribed medicine regimens. Similar studies to explore the use of HMs by other ethnic groups are imperative to help optimise pharmaceutical care of patients. Copyright © 2017 John Wiley & Sons, Ltd.
QFT bounds for robust stability specifications defined on the open‐loop function
Authors: Rico‐Azagra J. , Gil‐Martínez M. , Rico R. , Maisterra P. 
Published: September 2017

SummaryIn the framework of quantitative feedback theory, this paper develops a new method to compute robust stability bounds. This is of special interest when stability is defined directly on the open‐loop function. Thus, ignorance of the plant gain and phase shift can be specifically and independently considered. Furthermore, upper and lower stability margins for both gain and phase can be chosen. However, classical quantitative feedback theory stability specifications are defined as constraining the peak magnitude of closed‐loop functions, which lack the said flexibility. Once the upper tolerance has been defined, all stability margins are determined. Moreover, confining the most restrictive stability margin may result in other excessive margins. However, the stability bounds of the new approach guard just the required distance from the open‐loop frequency response to the critical point. This allows maximization of the available feedback in the functional bandwidth and minimization of the cost of feedback beyond the crossover frequency, provided that the open‐loop frequency response is shaped to closely follow the stability bounds. It should be noted that the new bound computation algorithm performs few and simple arithmetic operations. This makes it far more efficient than traditional methods. The flight altitude control of an unmanned aerial vehicle is proposed as a practical example to show the new method's potential benefits.
Tuning of CO2 Reduction Selectivity on Metal Electrocatalysts
Authors: Wang Yuhang , Liu Junlang , Wang Yifei , Al‐Enizi Abdullah M. , Zheng Gengfeng 
Published: September 2017

AbstractClimate change, caused by heavy CO2 emissions, is driving new demands to alleviate the rising concentration of atmospheric CO2 levels. Enlightened by the photosynthesis of green plants, photo(electro)chemical catalysis of CO2 reduction, also known as artificial photosynthesis, is emerged as a promising candidate to address these demands and is widely investigated during the past decade. Among various artificial photosynthetic systems, solar‐driven electrochemical CO2 reduction is widely recognized to possess high efficiencies and potentials for practical application. The efficient and selective electroreduction of CO2 is the key to the overall solar‐to‐chemical efficiency of artificial photosynthesis. Recent studies show that various metallic materials possess the capability to play as electrocatalysts for CO2 reduction. In order to achieve high selectivity for CO2 reduction products, various efforts are made including studies on electrolytes, crystal facets, oxide‐derived catalysts, electronic and geometric structures, nanostructures, and mesoscale phenomena. In this Review, these methods for tuning the selectivity of CO2 electrochemical reduction of metallic catalysts are summarized. The challenges and perspectives in this field are also discussed.
Myeloid Zinc Finger 1 and GA Binding Protein Co-Operate with Sox2 in Regulating the Expression of Yes-Associated Protein 1 in Cancer Cells
Authors: Verma Narendra Kumar , Gadi Abhilash , Maurizi Giulia , Roy Upal Basu , Mansukhani Alka , Basilico Claudio 
Published: September 2017

Abstract
The transcription factor (TF) yes-associated protein 1 (YAP1) is a major effector of the tumor suppressive Hippo signaling pathway and is also necessary to maintain pluripotency in embryonic stem cells. Elevated levels of YAP1 expression antagonize the tumor suppressive effects of the Hippo pathway that normally represses YAP1 function. High YAP1 expression is observed in several types of human cancers and is particularly prominent in cancer stem cells (CSCs). The stem cell TF Sox2, which marks and maintains CSCs in osteosarcomas (OSs), promotes YAP1 expression by binding to an intronic enhancer element and YAP1 expression is also crucial for the maintainance of OS stem cells. To further understand the regulation of YAP1 expression in OSs, we subjected the YAP1 intronic enhancer to scanning mutagenesis to identify all DNA cis-elements critical for enhancer function. Through this approach, we identified two novel TFs, GA binding protein (GABP) and myeloid zinc finger 1 (MZF1), which are essential for basal YAP1 transcription. These factors are highly expressed in OSs and bind to distinct sites in the YAP1 enhancer. Depletion of either factor leads to drastically reduced YAP1 expression and thus a reversal of stem cell properties. We also found that YAP1 can regulate the expression of Sox2 by binding to two distinct DNA binding sites upstream and downstream of the Sox2 gene. Thus, Sox2 and YAP1 reinforce each others expression to maintain stemness and tumorigenicity in OSs, but the activity of MZF1 and GABP is essential for YAP1 transcription.
Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development
Authors: Kim Yong Kyun , Refaeli Ido , Brooks Craig R. , Jing Peifeng , Gulieva Ramila E. , Hughes Michael R. , Cruz Nelly M. , Liu Yannan , Churchill Angela J. , Wang Yuliang , Fu Hongxia , Pippin Jeffrey W. , Lin Lih Y. , Shankland Stuart J. , Vogl A. Wayne , McNagny Kelly M. , Freedman Benjamin S. 
Published: September 2017

Abstract
A critical event during kidney organogenesis is the differentiation of podocytes, specialized epithelial cells that filter blood plasma to form urine. Podocytes derived from human pluripotent stem cells (hPSC-podocytes) have recently been generated in nephron-like kidney organoids, but the developmental stage of these cells and their capacity to reveal disease mechanisms remains unclear. Here, we show that hPSC-podocytes phenocopy mammalian podocytes at the capillary loop stage (CLS), recapitulating key features of ultrastructure, gene expression, and mutant phenotype. hPSC-podocytes in vitro progressively establish junction-rich basal membranes (nephrin+podocin+ZO-1+) and microvillus-rich apical membranes (podocalyxin+), similar to CLS podocytes in vivo. Ultrastructural, biophysical, and transcriptomic analysis of podocalyxin-knockout hPSCs and derived podocytes, generated using CRISPR/Cas9, reveals defects in the assembly of microvilli and lateral spaces between developing podocytes, resulting in failed junctional migration. These defects are phenocopied in CLS glomeruli of podocalyxin-deficient mice, which cannot produce urine, thereby demonstrating that podocalyxin has a conserved and essential role in mammalian podocyte maturation. Defining the maturity of hPSC-podocytes and their capacity to reveal and recapitulate pathophysiological mechanisms establishes a powerful framework for studying human kidney disease and regeneration.
A review on statistical postprocessing methods for hydrometeorological ensemble forecasting
Authors: Li Wentao , Duan Qingyun , Miao Chiyuan , Ye Aizhong , Gong Wei , Di Zhenhua 
Published: September 2017

Computer simulation models have been widely used to generate hydrometeorological forecasts. As the raw forecasts contain uncertainties arising from various sources, including model inputs and outputs, model initial and boundary conditions, model structure, and model parameters, it is necessary to apply statistical postprocessing methods to quantify and reduce those uncertainties. Different postprocessing methods have been developed for meteorological forecasts (e.g., precipitation) and for hydrological forecasts (e.g., streamflow) due to their different statistical properties. In this paper, we conduct a comprehensive review of the commonly used statistical postprocessing methods for both meteorological and hydrological forecasts. Moreover, methods to generate ensemble members that maintain the observed spatiotemporal and intervariable dependency are reviewed. Finally, some perspectives on the further development of statistical postprocessing methods for hydrometeorological ensemble forecasting are provided.WIREs Water2017, 4:e1246. doi: 10.1002/wat2.1246This article is categorized under:Science of Water > MethodsScience of Water > Water Extremes
Models of convergent extension during morphogenesis
Authors: Shindo Asako 
Published: September 2017

Convergent extension (CE) is a fundamental and conserved collective cell movement that forms elongated tissues during embryonic development. Thus far, studies have demonstrated two different mechanistic models of collective cell movements during CE. The first, termed the crawling mode, was discovered in the process of notochord formation in Xenopus laevis embryos, and has been the established model of CE for decades. The second model, known as the contraction mode, was originally reported in studies of germband extension in Drosophila melanogaster embryos and was recently demonstrated to be a conserved mechanism of CE among tissues and stages of development across species. This review summarizes the two modes of CE by focusing on the differences in cytoskeletal behaviors and relative expression of cell adhesion molecules. The upstream molecules regulating these machineries are also discussed. There are abundant studies of notochord formation in X. laevis embryos, as this was one of the pioneering model systems in this field. Therefore, the present review discusses these findings as an approach to the fundamental biological question of collective cell regulation. WIREs Dev Biol 2018, 7:e293. doi: 10.1002/wdev.293This article is categorized under:

Early Embryonic Development > Gastrulation and Neurulation
Comparative Development and Evolution > Model Systems
‘Pathways to choice’ of care setting
Authors: HILLCOAT-NALLÉTAMBY SARAH 
Published: September 2017

ABSTRACTThis article aims to encourage critical reflection about the limitations of the rational choice approach as an explanatory insight to understanding older people's choice-making about their health or social care requirements. It develops an interpretive framework examining how older people engage in the process of choice-making when selecting a care option. Choice-making is conceptualised as a temporal, processual phenomenon, influenced by others, and characterised by an individual's behavioural responses to changing circumstance and lifecourse events. Data are from qualitative interviews with 29 older adults whose choice of care option involved moving to an extra-care setting in Wales (United Kingdom). Transcripts were coded using in-case and constant-comparison approaches, and analysis was undertaken using concepts ofengagementandtemporalityas elements of the choice-making process. Using an inductive approach, a typology of six different ‘pathways to choice’ of care setting was identified; these findings suggest that choosing a care option in later life is a diverse, interactive and time-bound social phenomenon, inadequately captured by the rational choice approach where it is understood more as an individualised, linear and logical process. Recognising that choice-making evolves through time as part of a process shaped by others means service providers will be better positioned to offer opportunities for more preventative-focused interventions which empower older consumers to make planned and informed choices about care options.
A bridge to systems thinking in engineering design: An examination of students’ ability to identify functions at varying levels of abstraction
Authors: Tomko Megan , Nelson Jacob , Nagel Robert L. , Bohm Matthew , Linsey Julie 
Published: September 2017

AbstractThis paper aims to situate functional abstraction in light of systems thinking. While function does not extensively appear in systems thinking literature, the literature does identify function as part of systems thinking that enables us to recognize and connect that function has a role in building a systems thinking approach for students. A systems thinking approach is valuable for students since it helps them view a system holistically. In this research, we measure how well students are able to abstract function. We asked students to generate functions for two different products and examined how students taught functional modeling and function enumeration compare to students who are only taught function enumeration. The student responses were examined using a rubric that we developed and validated for assessing function. This rubric may be used to classify functions by correctness (correct, partially correct, and incorrect) and categories (high level, interface, low level, and ambiguous). On questions where students were not explicitly asked to write a high-level function or low-level function, and so on, students who were taught functional modeling were able to better demonstrate systems thinking in their responses (low-level and interface functions) than those students who were only taught function enumeration.
Outbreaks attributed to pork in the United States, 1998–2015
Authors: SELF J. L. , LUNA-GIERKE R. E. , FOTHERGILL A. , HOLT K. G. , VIEIRA A. R. 
Published: September 2017

SUMMARYEach year in the United States, an estimated 525 000 infections, 2900 hospitalizations, and 82 deaths are attributed to consumption of pork. We analyzed the epidemiology of outbreaks attributed to pork in the United States reported to the Centers for Disease Control and Prevention (CDC) 1998–2015. During that period, 288 outbreaks were attributed to pork, resulting in 6372 illnesses, 443 hospitalizations, and four deaths. The frequency of outbreaks attributed to pork decreased by 37% during this period, consistent with a decline in total foodborne outbreaks. However, outbreaks attributed to pork increased by 73% in 2015 (19 outbreaks) compared with the previous 3 years (average of 11 outbreaks per year), without a similar increase in total foodborne outbreaks. Most (>99%) of these outbreaks occurred among people exposed in the same state. The most frequent etiology shifted fromStaphylococcus aureustoxin during 1998–2001 (19%) toSalmonelladuring 2012–2015 (46%). Outbreaks associated with ham decreased from eight outbreaks per year during 1998–2001, to one per year during 2012–2015 (P< 0·01). Additional efforts are necessary to reduce outbreaks and sporadic illnesses associated with pork products.
Food insecurity and emotional health in the USA: a systematic narrative review of longitudinal research
Authors: Bruening Meg , Dinour Lauren M , Chavez Jose B Rosales 
Published: September 2017

AbstractObjectiveTo examine the causal directionality in the relationship between food insecurity and emotional well-being among US-based populations.DesignSystematic literature review from January 2006 to July 2016 using MEDLINE (PubMed), PsychInfo, Web of Science and CINHAL. Inclusion criteria were: written in English; examined a longitudinal association between food insecurity and emotional well-being.SettingThe USA.SubjectsChildren and adults.ResultsTwelve out of 4161 peer-reviewed articles met inclusion criteria. Three articles examined the effect of emotional well-being on food insecurity, five studies examined the effect of food insecurity on emotional well-being, and four studies examined a bidirectional relationship. Most studies (83 %) reported a positive relationship between negative emotional well-being and food insecurity over time.ConclusionsFindings suggest a bidirectional association whereby food insecurity increases the risk of poor emotional health, and poor emotional health increases the risk of food insecurity. Better-constructed studies are needed to follow cohorts at risk for both food insecurity and poor emotional health to further understand the mediators and moderators of the relationships. Intervention studies designed to mitigate or reverse risks are also needed to determine best evidence for practice and policy.