bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and localization of epithelial stem cell and differentiation markers in equine skin, eye and hoof
Authors: Linardi Renata L. , Megee Susan O. , Mainardi Sarah R. , Senoo Makoto , Galantino‐Homer Hannah L. 
Published: May 2015

BackgroundThe limited characterization of equine skin, eye and hoof epithelial stem cell (ESC) and differentiation markers impedes the investigation of the physiology and pathophysiology of these tissues.Hypothesis/ObjectivesTo characterizeESCand differentiation marker expression in epithelial tissues of the equine eye, haired skin and hoof capsule.MethodsIndirect immunofluorescence microscopy and immunoblotting were used to detect expression and tissue localization of keratin (K) isoforms K3, K10, K14 and K124, the transcription factor p63 (a marker ofESCs) and phosphorylated p63 [pp63; a marker ofESCtransition to transit‐amplifying (TA) cell] in epithelial tissues of the foot (haired skin, hoof coronet and hoof lamellae) and the eye (limbus and cornea).ResultsExpression of K14 was restricted to the basal layer of epidermal lamellae and to basal and adjacent suprabasal layers of the haired skin, coronet and corneal limbus. Coronary and lamellar epidermis was negative for both K3 and K10, which were expressed in the cornea/limbus epithelium and haired skin epidermis, respectively. Variable expression of p63 with relatively low to high levels of phosphorylation was detected in individual basal and suprabasal cells of all epithelial tissues examined.ConclusionsTo the best of the author's knowledge, this is the first report of the characterization of tissue‐specific keratin marker expression and the localization of putative epithelial progenitor cell populations, includingESCs (high p63 expression with low pp63 levels) andTAcells (high expression of both p63 and pp63), in the horse. These results will aid further investigation of epidermal and corneal epithelial biology and regenerative therapies in horses.
Resina Draconis as a topical treatment for pressure ulcers: A systematic review and meta‐analysis
Authors: Xu Jiaqi , Xiong Tian , Yang Ying , Li Jie , Mao Jing 
Published: May 2015

ABSTRACTIn recent years, a number of studies have reported on Resina Draconis (RD) as a topical treatment for pressure ulcers. To evaluate these studies, we performed a systematic review and meta‐analysis aimed to examine the efficacy of RD for pressure ulcers. We searched eight electronic databases to identify randomized controlled trials in which RD treatment was compared with other topical treatment of pressure ulcers from 1980 to 2014. Selection of studies, study appraisal, data extraction and analysis were undertaken using standard methods. Fourteen randomized controlled trials were included involving 618 patients. The results of the meta‐analysis showed that, RD treatment was significantly associated with a higher healing rate for pressure ulcers (risk ratio 2.07, 95% confidence intervals 1.73–2.48, p < 0.001). The results of descriptive analysis showed that, compared with the control group, RD treatment shortened healing time. As for safety, adverse reactions had not been reported. These results suggest that RD can improve the healing rate for pressure ulcers and shorten the healing time, compared with other topical treatments. However, due to limited quality and quantity of the included studies, this conclusion needs to be proved by more high quality studies.
Objective Analysis of Preschoolers’ Physical Activity Patterns During Free Playtime
Authors: Greever Cory J. , Sirard John , Alhassan Sofiya 
Published: May 2015

Background:The purpose of this study was to examine the temporal patterns of preschoolers’ physical activity (PA) levels during a typical outdoor free playtime.Methods:Baseline playtime accelerometer counts (4.3 ± 0.8 days) from 3 preschool PA intervention studies were used (n = 326 children, age = 4.0 ± 0.8 years). Data were collected using 15-second epochs and classified into sedentary, light, or moderate-tovigorous physical activity (MVPA). Patterns of change during playtime were analyzed using orthogonal polynomial comparisons.Results:For all ages, there was a U-shaped pattern of change for the percent of epochs classified as sedentary [F(1, 323) = 47.12, P < .001) and an inverted U-shaped pattern of change for the percent of epochs classified as MVPA [F(1,323) = 32.15, P < .001]. Age-stratified analyses indicated that the 3-year-olds maintained the decrease in sedentary time [F(2,323) = 6.408, P = .002] and the increase in MVPA [F(2,323) = 3.2, P = .04] to a greater extent than the 4- and 5-year-olds.Conclusions:Preschool children gradually became more active during the first 10 to 15 minutes of outdoor gross motor playtime and less active over the final 10 to 15 minutes of playtime. During the second half of playtime 3-year-olds maintained these changes to a greater degree than 4- and 5-year-olds.
Walking and Walkability: Is Wayfinding a Missing Link? Implications for Public Health Practice
Authors: Vandenberg Ann E. , Hunter Rebecca H. , Anderson Lynda A. , Bryant Lucinda L. , Hooker Steven P. , Satariano William A. 
Published: May 2015

Background:Research on walking and walkability has yet to focus on wayfinding, the interactive, problem-solving process by which people use environmental information to locate themselves and navigate through various settings.Methods:We reviewed the literature on outdoor pedestrian-oriented wayfinding to examine its relationship to walking and walkability, 2 areas of importance to physical activity promotion.Results:Our findings document that wayfinding is cognitively demanding and can compete with other functions, including walking itself. Moreover, features of the environment can either facilitate or impede wayfinding, just as environmental features can influence walking.Conclusions:Although there is still much to be learned about wayfinding and walking behaviors, our review helps frame the issues and lays out the importance of this area of research and practice.
In Vitro
Activity of Aztreonam-Avibactam against a Global Collection of Gram-Negative Pathogens from 2012 and 2013
Authors: Biedenbach Douglas J. , Kazmierczak Krystyna , Bouchillon Samuel K. , Sahm Daniel F. , Bradford Patricia A. 
Published: May 2015

ABSTRACT

The combination of aztreonam plus avibactam is being developed for use in infections caused by metallo-β-lactamase-producing
Enterobacteriaceae
strains that also produce serine β-lactamases. The
in vitro
activities of aztreonam-avibactam and comparator antimicrobials were determined against year 2012 and 2013 clinical isolates of
Enterobacteriaceae
,
Pseudomonas aeruginosa
, and
Acinetobacter baumannii
using the broth microdilution methodology recommended by the Clinical and Laboratory Standards Institute (CLSI). A total of 28,501 unique clinical isolates were obtained from patients in 190 medical centers within 39 countries. MIC
90
values of aztreonam and aztreonam-avibactam against all collected isolates of
Enterobacteriaceae
(
n
= 23,516) were 64 and 0.12 μg/ml, respectively, with 76.2% of the isolates inhibited by ≤4 μg/ml of aztreonam (the CLSI breakpoint) and 99.9% of the isolates inhibited by ≤4 μg/ml of aztreonam-avibactam using a fixed concentration of 4 μg/ml of avibactam. The MIC
90
was 32 μg/ml for both aztreonam and aztreonam-avibactam against
P. aeruginosa
(
n
= 3,766). Aztreonam alone or in combination with avibactam had no
in vitro
activity against isolates of
A. baumannii
. PCR and sequencing were used to characterize 5,076 isolates for β-lactamase genes. Aztreonam was not active against most
Enterobacteriaceae
isolates producing class A or class C enzymes alone or in combination with class B metallo-β-lactamases. In contrast, >99% of
Enterobacteriaceae
isolates producing all observed Ambler classes of β-lactamase enzymes were inhibited by ≤4 μg/ml aztreonam in combination with avibactam, including isolates that produced IMP-, VIM-, and NDM-type metallo-β-lactamases in combination with multiple serine β-lactamases.
Evaluating the Pharmacodynamic Effect of Antimalarial Drugs in Clinical Trials by Quantitative PCR
Authors: Marquart Louise , Baker Mark , O'Rourke Peter , McCarthy James S. 
Published: May 2015

ABSTRACT
The ongoing development of new antimalarial drugs and the increasing use of controlled human malaria infection (CHMI) studies to investigate their activity in early-stage clinical trials require the development of methods to analyze their pharmacodynamic effect. This is especially so for studies where quantitative PCR (qPCR) is becoming the preferred method for assessing parasite clearance as the study endpoint. We report the development and validation of an analytic approach for qPCR-determined parasite clearance data. First, in a clinical trial with the licensed antimalarial combination sulfadoxine-pyrimethamine (S/P), qPCR data were collected from 12 subjects and used to determine qPCR replicate variability and to identify outliers. Then, an iterative analytic approach based on modeling the log-linear decay of parasitemia following drug treatment was developed to determine the parasite reduction ratio (PRR) and parasite clearance half-life, both measures of parasite clearance. This analytic approach was then validated with data from 8 subjects enrolled in a second study with the licensed antimalarial drug mefloquine. By this method, the PRR and parasite clearance half-lives for S/P and Mefloquine were determined to be 38,878 (95% confidence interval [95% CI], 17,396 to 86,889) at 3.15 (95% CI, 2.93 to 3.41) days and 157 (95% CI, 130 to 189) at 6.58 (95% CI, 6.35 to 6.83) days for the respective studies. No serious adverse events occurred in the two trials, and pharmacokinetic values were within expected ranges for sulfadoxine and pyrimethamine. The robust statistical method that we have developed to analyze qPCR-derived pharmacodynamic data from CHMI studies will facilitate the assessment of the activity of a range of experimental antimalarial drugs now entering clinical trials. (This trial was registered with the Australian New Zealand Clinical Trials Registry under registration numbers ACTRN12611001203943 and ACTRN12612000323820.)
In Vitro
Activity of Daptomycin in Combination with β-Lactams, Gentamicin, Rifampin, and Tigecycline against Daptomycin-Nonsusceptible Enterococci
Authors: Hindler Janet A. , Wong-Beringer Annie , Charlton Carmen L. , Miller Shelley A. , Kelesidis Theodoros , Carvalho Marissa , Sakoulas George , Nonejuie Poochit , Pogliano Joseph , Nizet Victor , Humphries Romney 
Published: May 2015

ABSTRACT

Enterococci that are nonsusceptible (NS; MIC > 4 μg/ml) to daptomycin are an emerging clinical concern. The synergistic combination of daptomycin plus beta-lactams has been shown to be effective against vancomycin-resistant
Enterococcus
(VRE) species
in vitro
. This study systematically evaluated by
in vitro
time-kill studies the effect of daptomycin in combination with ampicillin, cefazolin, ceftriaxone, ceftaroline, ertapenem, gentamicin, tigecycline, and rifampin, for a collection of 9 daptomycin-NS enterococci that exhibited a broad range of MICs and different resistance-conferring mutations. We found that ampicillin plus daptomycin yielded the most consistent synergy but did so only for isolates with mutations to the
liaFSR
system. Daptomycin binding was found to be enhanced by ampicillin in a representative isolate with such mutations but not for an isolate with mutation to the
yycFGHIJ
system. In contrast, ampicillin enhanced the killing of the LL-37 human antimicrobial peptide against daptomycin-NS
E. faecium
with either the
liaFSR
or
yycFGHIJ
mutation. Antagonism was noted only for rifampin and tigecycline and only for 2 or 3 isolates. These data add support to the growing body of evidence indicating that therapy combining daptomycin and ampicillin may be helpful in eradicating refractory VRE infections.
Role of Phenol-Soluble Modulins in Formation of Staphylococcus aureus Biofilms in Synovial Fluid
Authors: Dastgheyb Sana S. , Villaruz Amer E. , Le Katherine Y. , Tan Vee Y. , Duong Anthony C. , Chatterjee Som S. , Cheung Gordon Y. C. , Joo Hwang-Soo , Hickok Noreen J. , Otto Michael 
Published: May 2015

ABSTRACT

Staphylococcus aureus
is a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specific
S. aureus
surface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such as the polysaccharide intercellular adhesin (PIA), with the bacterial cell surface. Together, our findings support a two-step model of staphylococcal prosthetic joint infection: As we previously reported, interaction of
S. aureus
surface proteins with host matrix proteins such as fibrin initiates agglomeration; our present results show that, thereafter, the bacterial agglomerates grow to extremely large sizes owing to the lack of PSM expression under the specific conditions present in joints. Our findings provide a mechanistic explanation for the reported extreme resistance of joint infection to antibiotic treatment, lend support to the notions that Agr functionality and PSM production play a major role in defining different forms of
S. aureus
infection, and have important implications for antistaphylococcal therapeutic strategies.
Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis
Authors: Kim Paul D. , Xia-Juan Xia , Crump Katie E. , Abe Toshiharu , Hajishengallis George , Sahingur Sinem E. 
Published: May 2015

ABSTRACT

Chronic periodontitis is a local inflammatory disease induced by a dysbiotic microbiota and leading to destruction of the tooth-supporting structures. Microbial nucleic acids are abundantly present in the periodontium, derived through release after phagocytic uptake of microbes and/or from biofilm-associated extracellular DNA. Binding of microbial DNA to its cognate receptors, such as Toll-like receptor 9 (TLR9), can trigger inflammation. In this study, we utilized TLR9 knockout (TLR9
−/−
) mice and wild-type (WT) controls in a murine model of
Porphyromonas gingivalis
-induced periodontitis and report the first
in vivo
evidence that TLR9 signaling mediates the induction of periodontal bone loss.
P. gingivalis
-infected WT mice exhibited significantly increased bone loss compared to that in sham-infected WT mice or
P. gingivalis
-infected TLR9
−/−
mice, which were resistant to bone loss. Consistent with this, the expression levels of interleukin 6 (IL-6), tumor necrosis factor (TNF), and receptor-activator of nuclear factor kappa B ligand (RANKL) were significantly elevated in the gingival tissues of the infected WT mice but not in infected TLR9
−/−
mice compared to their levels in controls.
Ex vivo
studies using splenocytes and bone marrow-derived macrophages revealed significantly diminished cytokine production in TLR9
−/−
cells relative to the cytokine production in WT cells in response to
P. gingivalis
, thereby implicating TLR9 in inflammatory responses to this organism. Intriguingly, compared to the cytokine production in WT cells, TLR9
−/−
cells exhibited significantly decreased proinflammatory cytokine production upon challenge with lipopolysaccharide (LPS) (TLR4 agonist) or Pam3Cys (TLR2 agonist), suggesting possible cross talk between TLR9, TLR4, and TLR2. Collectively, our results provide the first proof-of-concept evidence implicating TLR9-triggered inflammation in periodontal disease pathogenesis, thereby identifying a new potential therapeutic target to control periodontal inflammation.
Progressive supra-nuclear palsy: frequency of cardinal extrapyramidal features at first presentation
Authors: Pradhan Sunil , Tandon Ruchika 
Published: May 2015

ABSTRACT

Objectives
Cardinal extrapyramidal features of progressive supranuclear palsy (PSP) help in clinically differentiating this condition from Parkinson's disease and other Parkinsonian syndromes. However, not all extrapyramidal features may be initially present, thus posing a difficulty in early diagnosis. We studied their frequency at the time of first presentation.

Methods
Patients diagnosed clinically with PSP using the National Institute for Neurological Disorders and Society for PSP (NINDS/SPSP) criteria and seen between August 2010 and April 2013 were examined for the presence, ‘presence with deviation’ or absence of six extrapyramidal features: axial rigidity, symmetry, extended posture, backward falls, absence of tremors and lack of levodopa response.

Results
Twenty-eight patients (mean (SD) age 64.86 (9.72) years; 16 (57%) men) met the inclusion criteria. Of these, 14% had all six extrapyramidal features associated with PSP, 39% had five, 29% had four, 14% had three and 4% had two. The most frequent extrapyramidal sign was axial rigidity (68%). Axial plus peripheral rigidity was found in 18% of patients and peripheral rigidity alone in 14%. Extrapyramidal features were symmetrical in 29% and asymmetrical beyond 1 year in 29%. Body posture was extended in 46% and flexed in 21%. Backward falls were found in 50% and forward falls in 11%. Pill-rolling tremors were observed in 29%. Response to levodopa therapy was poor in 21% and good beyond 6 months in 39%.

Conclusions
Only 14% of PSP patients present with all six cardinal extrapyramidal features. Also, deviations from standard descriptions are common in the initial stages of disease.
The elusive Rivera-Cocos plate boundary: not diffuse
Authors: Alvarez Román , Yutsis Vsevolod 
Published: May 2015

Abstract
Inland and offshore gravimetric determinations in the Southern Colima rift in western Mexico allowed for the construction of a Bouguer anomaly map of the area. Four submarine canyons of tectonic relevance are located in the offshore area. Gravimetric models of the oceanic subducting slab were calculated from the residual Bouguer anomaly along six trench-parallel lines and three trench-perpendicular lines including the area of the canyons. The former lines show considerable distortion of the slab that we attribute to compression, while the latter show distinct dipping angles of the oceanic slab at distances of around 75 km from the trench: the westernmost line shows a dip angle of 55° between depths of 20 and 70 km, while the easternmost shows a dip angle of 32° at depths between 18 and 50 km. We submit that the former represents a section of the subducting Rivera plate, and the latter represents a section of the Cocos plate. Extracting coordinates of representative points on the surface of the nine slab models allowed for a reconstruction of the slab surface: the transition from the Rivera to the Cocos plate is marked by topographic gradients in the modelled slab surface suggesting the trajectory of the boundary between the plates. We propose a tectonic model that includes a transpression zone involving the marine platform and the Southern Colima rift and a transtension zone in the Northern Colima rift: the Colima Volcanic Complex is located in the transition zone between them.
Effect handlers in scope
Authors: Wu Nicolas , Schrijvers Tom , Hinze Ralf 
Published: May 2015

Algebraic effect handlers are a powerful means for describing effectful computations. They provide a lightweight and orthogonal technique to define and compose the syntax and semantics of different effects. The semantics is captured by handlers, which are functions that transform syntax trees.
Unfortunately, the approach does not support syntax for scoping constructs, which arise in a number of scenarios. While handlers can be used to provide a limited form of scope, we demonstrate that this approach constrains the possible interactions of effects and rules out some desired semantics.
This paper presents two different ways to capture scoped constructs in syntax, and shows how to achieve different semantics by reordering handlers. The first approach expresses scopes using the existing algebraic handlers framework, but has some limitations. The problem is fully solved in the second approach where we introduce higher-order syntax.
Safe & Efficient Gradual Typing for TypeScript
Authors: Rastogi Aseem , Swamy Nikhil , Fournet Cédric , Bierman Gavin , Vekris Panagiotis 
Published: May 2015

Current proposals for adding gradual typing to JavaScript, such as Closure, TypeScript and Dart, forgo soundness to deal with issues of scale, code reuse, and popular programming patterns. We show how to address these issues in practice while retaining soundness. We design and implement a new gradual type system, prototyped for expediency as a 'Safe' compilation mode for TypeScript. Our compiler achieves soundness by enforcing stricter static checks and embedding residual runtime checks in compiled code. It emits plain JavaScript that runs on stock virtual machines. Our main theorem is a simulation that ensures that the checks introduced by Safe TypeScript (1) catch any dynamic type error, and (2) do not alter the semantics of type-safe TypeScript code.
Safe TypeScript is carefully designed to minimize the performance overhead of runtime checks. At its core, we rely on two new ideas: differential subtyping, a new form of coercive subtyping that computes the minimum amount of runtime type information that must be added to each object; and an erasure modality, which we use to safely and selectively erase type information. This allows us to scale our design to full-fledged TypeScript, including arrays, maps, classes, inheritance, overloading, and generic types.
We validate the usability and performance of Safe TypeScript empirically by type-checking and compiling around 120,000 lines of existing TypeScript source code. Although runtime checks can be expensive, the end-to-end overhead is small for code bases that already have type annotations. For instance, we bootstrap the Safe TypeScript compiler (90,000 lines including the base TypeScript compiler): we measure a 15% runtime overhead for type safety, and also uncover programming errors as type safety violations. We conclude that, at least during development and testing, subjecting JavaScript/TypeScript programs to safe gradual typing adds significant value to source type annotations at a modest cost.