bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel‐scanning tomosynthesis using a slot scanning technique: Fixed‐focus reconstruction and the resulting image quality
Authors: Shibata Koichi , Notohara Daisuke , Sakai Takihito
Published: October 2014

Purpose:

Parallel‐scanning tomosynthesis (PS‐TS) is a novel technique that fuses the slot scanning technique and the conventional tomosynthesis (TS) technique. This approach allows one to obtain long‐view tomosynthesis images in addition to normally sized tomosynthesis images, even when using a system that has no linear tomographic scanning function. The reconstruction technique and an evaluation of the resulting image quality for PS‐TS are described in this paper.

Methods:

The PS‐TS image‐reconstruction technique consists of several steps (1) the projection images are divided into strips, (2) the strips are stitched together to construct images corresponding to the reconstruction plane, (3) the stitched images are filtered, and (4) the filtered stitched images are back‐projected. In the case of PS‐TS using the fixed‐focus reconstruction method (PS‐TS‐F), one set of stitched images is used for the reconstruction planes at all heights, thus avoiding the necessity of repeating steps (1)–(3). A physical evaluation of the image quality of PS‐TS‐F compared with that of the conventional linear TS was performed using a R/F table (Sonialvision safire, Shimadzu Corp., Kyoto, Japan). The tomographic plane with the best theoretical spatial resolution (the in‐focus plane, IFP) was set at a height of 100 mm from the table top by adjusting the reconstruction program. First, the spatial frequency response was evaluated at heights of −100, −50, 0, 50, 100, and 150 mm from the IFP using the edge of a 0.3‐mm‐thick copper plate. Second, the spatial resolution at each height was visually evaluated using an x‐ray test pattern (Model No. 38, PTW Freiburg, Germany). Third, the slice sensitivity at each height was evaluated via the wire method using a 0.1‐mm‐diameter tungsten wire. Phantom studies using a knee phantom and a whole‐body phantom were also performed.

Results:

The spatial frequency response of PS‐TS‐F yielded the best results at the IFP and degraded slightly as the distance from the IFP increased. A visual evaluation of the spatial resolution using the x‐ray test pattern indicated that the resolution was 1.8 lp/mm at the IFP and 1.2 lp/mm at heights of −100 and 100 mm from the IFP. The authors demonstrated that a spatial resolution of 1.2–1.8 lp/mm could be obtained within heights of 200 mm of the IFP. The slice sensitivity varied between 11.1 and 13.8 mm for heights between −50 and 100 mm, and there was no critical change in the slice sensitivity within a height range of 150 mm around the IFP. The phantom results demonstrated that tomosynthesis and long‐view images could be reconstructed.

Conclusions:

PS‐TS‐F provides tomosynthesis images while using low‐cost systems that have no tomographic scanning function, such as tableside‐controlled universal R/F systems or universal radiographic systems.
Extracellular Polymeric Substance Architecture Influences Natural Genetic Transformation of Acinetobacter baylyi in Biofilms
Authors: Merod Robin T. , Wuertz Stefan
Published: October 2014

Genetic exchange by natural transformation is an important mechanism of horizontal gene transfer in biofilms. Thirty-two biofilm metrics were quantified in a heavily encapsulated
Acinetobacter baylyi
strain and a miniencapsulated mutant strain, accounting for cellular architecture, extracellular polymeric substances (EPS) architecture, and their combined biofilm architecture. In general, transformation location, abundance, and frequency were more closely correlated to EPS architecture than to cellular or combined architecture. Transformation frequency and transformant location had the greatest correlation with the EPS metric surface area-to-biovolume ratio. Transformation frequency peaked when EPS surface area-to-biovolume ratio was greater than 3 μm
2
/μm
3
and less than 5 μm
2
/μm
3
. Transformant location shifted toward the biofilm-bulk fluid interface as the EPS surface area-to-biovolume ratio increased. Transformant biovolume was most closely correlated with EPS biovolume and peaked when transformation occurred in close proximity to the substratum. This study demonstrates that biofilm architecture influences
A. baylyi
transformation frequency and transformant location and abundance. The major role of EPS may be to facilitate the binding and stabilization of plasmid DNA for cellular uptake.
The Antimicrobial Mechanism of Action of Epsilon-Poly-
l
-Lysine
Authors: Hyldgaard Morten , Mygind Tina , Vad Brian S. , Stenvang Marcel , Otzen Daniel E. , Meyer Rikke L.
Published: October 2014

Epsilon-poly-
l
-lysine (ε-PL) is a natural antimicrobial cationic peptide which is generally regarded as safe (GRAS) as a food preservative. Although its antimicrobial activity is well documented, its mechanism of action is only vaguely described. The aim of this study was to clarify ε-PL's mechanism of action using
Escherichia coli
and
Listeria innocua
as model organisms. We examined ε-PL's effect on cell morphology and membrane integrity and used an array of
E. coli
deletion mutants to study how specific outer membrane components affected the action of ε-PL. We furthermore studied its interaction with lipid bilayers using membrane models.
In vitro
cell studies indicated that divalent cations and the heptose I and II phosphate groups in the lipopolysaccharide layer of
E. coli
are critical for ε-PL's binding efficiency. ε-PL removed the lipopolysaccharide layer and affected cell morphology of
E. coli
, while
L. innocua
underwent minor morphological changes. Propidium iodide staining showed that ε-PL permeabilized the cytoplasmic membrane in both species, indicating the membrane as the site of attack. We compared the interaction with neutral or negatively charged membrane systems and showed that the interaction with ε-PL relied on negative charges on the membrane. Suspended membrane vesicles were disrupted by ε-PL, and a detergent-like disruption of
E. coli
membrane was confirmed by atomic force microscopy imaging of supported lipid bilayers. We hypothesize that ε-PL destabilizes membranes in a carpet-like mechanism by interacting with negatively charged phospholipid head groups, which displace divalent cations and enforce a negative curvature folding on membranes that leads to formation of vesicles/micelles.
Investigating the Function of an Arabinan Utilization Locus Isolated from a Termite Gut Community
Authors: Arnal Grégory , Bastien Géraldine , Monties Nelly , Abot Anne , Anton Leberre Véronique , Bozonnet Sophie , O'Donohue Michael , Dumon Claire
Published: October 2014

Biocatalysts are essential for the development of bioprocesses efficient for plant biomass degradation. Previously, a metagenomic clone containing DNA from termite gut microbiota was pinpointed in a functional screening that revealed the presence of arabinofuranosidase activity. Subsequent genetic and bioinformatic analysis revealed that the DNA fragment belonged to a member of the genus
Bacteroides
and encoded 19 open reading frames (ORFs), and annotation suggested the presence of hypothetical transporter and regulator proteins and others involved in the catabolism of pentose sugar. In this respect and considering the phenotype of the metagenomic clone, it was noted that among the ORFs, there are four putative arabinose-specific glycoside hydrolases, two from family GH43 and two from GH51. In this study, a thorough bioinformatics analysis of the metagenomic clone gene cluster has been performed and the four aforementioned glycoside hydrolases have been characterized. Together, the results provide evidence that the gene cluster is a polysaccharide utilization locus dedicated to the breakdown of the arabinan component in pectin and related substrates. Characterization of the two GH43 and the two GH51 glycoside hydrolases has revealed that each of these enzymes displays specific catalytic capabilities and that when these are combined the enzymes act synergistically, increasing the efficiency of arabinan degradation.
The Western Progression of Lyme Disease: Infectious and Nonclonal
Borrelia burgdorferi Sensu Lato
Populations in Grand Forks County, North Dakota
Authors: Stone Brandee L. , Russart Nathan M. , Gaultney Robert A. , Floden Angela M. , Vaughan Jefferson A. , Brissette Catherine A.
Published: October 2014

Scant attention has been paid to Lyme disease,
Borrelia burgdorferi
,
Ixodes scapularis
, or reservoirs in eastern North Dakota despite the fact that it borders high-risk counties in Minnesota. Recent reports of
B. burgdorferi
and
I. scapularis
in North Dakota, however, prompted a more detailed examination. Spirochetes cultured from the hearts of five rodents trapped in Grand Forks County, ND, were identified as
B. burgdorferi sensu lato
through sequence analyses of the 16S rRNA gene, the 16S rRNA gene-
ileT
intergenic spacer region,
flaB
,
ospA
,
ospC
, and
p66
. OspC typing revealed the presence of groups A, B, E, F, L, and I. Two rodents were concurrently carrying multiple OspC types. Multilocus sequence typing suggested the eastern North Dakota strains are most closely related to those found in neighboring regions of the upper Midwest and Canada. BALB/c mice were infected with
B. burgdorferi
isolate M3 (OspC group B) by needle inoculation or tick bite. Tibiotarsal joints and ear pinnae were culture positive, and
B. burgdorferi
M3 was detected by quantitative PCR (qPCR) in the tibiotarsal joints, hearts, and ear pinnae of infected mice. Uninfected larval
I. scapularis
ticks were able to acquire
B. burgdorferi
M3 from infected mice; M3 was maintained in
I. scapularis
during the molt from larva to nymph; and further, M3 was transmitted from infected
I. scapularis
nymphs to naive mice, as evidenced by cultures and qPCR analyses. These results demonstrate that isolate M3 is capable of disseminated infection by both artificial and natural routes of infection. This study confirms the presence of unique (nonclonal) and infectious
B. burgdorferi
populations in eastern North Dakota.
Isolation of Acetogenic Bacteria That Induce Biocorrosion by Utilizing Metallic Iron as the Sole Electron Donor
Authors: Kato Souichiro , Yumoto Isao , Kamagata Yoichi
Published: October 2014

Corrosion of iron occurring under anoxic conditions, which is termed microbiologically influenced corrosion (MIC) or biocorrosion, is mostly caused by microbial activities. Microbial activity that enhances corrosion via uptake of electrons from metallic iron [Fe(0)] has been regarded as one of the major causative factors. In addition to sulfate-reducing bacteria and methanogenic archaea in marine environments, acetogenic bacteria in freshwater environments have recently been suggested to cause MIC under anoxic conditions. However, no microorganisms that perform acetogenesis-dependent MIC have been isolated or had their MIC-inducing mechanisms characterized. Here, we enriched and isolated acetogenic bacteria that induce iron corrosion by utilizing Fe(0) as the sole electron donor under freshwater, sulfate-free, and anoxic conditions. The enriched communities produced significantly larger amounts of Fe(II) than the abiotic controls and produced acetate coupled with Fe(0) oxidation prior to CH
4
production. Microbial community analysis revealed that
Sporomusa
sp. and
Desulfovibrio
sp. dominated in the enrichments. Strain GT1, which is closely related to the acetogen
Sporomusa sphaeroides
, was eventually isolated from the enrichment. Strain GT1 grew acetogenetically with Fe(0) as the sole electron donor and enhanced iron corrosion, which is the first demonstration of MIC mediated by a pure culture of an acetogen. Other well-known acetogenic bacteria, including
Sporomusa ovata
and
Acetobacterium
spp., did not grow well on Fe(0). These results indicate that very few species of acetogens have specific mechanisms to efficiently utilize cathodic electrons derived from Fe(0) oxidation and induce iron corrosion.
Proximity Effect among Cellulose-Degrading Enzymes Displayed on the Saccharomyces cerevisiae Cell Surface
Authors: Bae Jungu , Kuroda Kouichi , Ueda Mitsuyoshi
Published: October 2014

Proximity effect is a form of synergistic effect exhibited when cellulases work within a short distance from each other, and this effect can be a key factor in enhancing saccharification efficiency. In this study, we evaluated the proximity effect between 3 cellulose-degrading enzymes displayed on the
Saccharomyces cerevisiae
cell surface, that is, endoglucanase, cellobiohydrolase, and β-glucosidase. We constructed 2 kinds of arming yeasts through genome integration: ALL-yeast, which simultaneously displayed the 3 cellulases (thus, the different cellulases were near each other), and MIX-yeast, a mixture of 3 kinds of single-cellulase-displaying yeasts (the cellulases were far apart). The cellulases were tagged with a fluorescence protein or polypeptide to visualize and quantify their display. To evaluate the proximity effect, we compared the activities of ALL-yeast and MIX-yeast with respect to degrading phosphoric acid-swollen cellulose after adjusting for the cellulase amounts. ALL-yeast exhibited 1.25-fold or 2.22-fold higher activity than MIX-yeast did at a yeast concentration equal to the yeast cell number in 1 ml of yeast suspension with an optical density (OD) at 600 nm of 10 (OD10) or OD0.1. At OD0.1, the distance between the 3 cellulases was greater than that at OD10 in MIX-yeast, but the distance remained the same in ALL-yeast; thus, the difference between the cellulose-degrading activities of ALL-yeast and MIX-yeast increased (to 2.22-fold) at OD0.1, which strongly supports the proximity effect between the displayed cellulases. A proximity effect was also observed for crystalline cellulose (Avicel). We expect the proximity effect to further increase when enzyme display efficiency is enhanced, which would further increase cellulose-degrading activity. This arming yeast technology can also be applied to examine proximity effects in other diverse fields.
Acquisition of the Ability To Assimilate Mannitol by Saccharomyces cerevisiae through Dysfunction of the General Corepressor Tup1-Cyc8
Authors: Chujo Moeko , Yoshida Shiori , Ota Anri , Murata Kousaku , Kawai Shigeyuki
Published: October 2014

Saccharomyces cerevisiae
normally cannot assimilate mannitol, a promising brown macroalgal carbon source for bioethanol production. The molecular basis of this inability remains unknown. We found that cells capable of assimilating mannitol arose spontaneously from wild-type
S. cerevisiae
during prolonged culture in mannitol-containing medium. Based on microarray data, complementation analysis, and cell growth data, we demonstrated that acquisition of mannitol-assimilating ability was due to spontaneous mutations in the genes encoding Tup1 or Cyc8, which constitute a general corepressor complex that regulates many kinds of genes. We also showed that an
S. cerevisiae
strain carrying a mutant allele of
CYC8
exhibited superior salt tolerance relative to other ethanologenic microorganisms; this characteristic would be highly beneficial for the production of bioethanol from marine biomass. Thus, we succeeded in conferring the ability to assimilate mannitol on
S. cerevisiae
through dysfunction of Tup1-Cyc8, facilitating production of ethanol from mannitol.
Effect of Transcutaneous Electrical Acupuncture Point Stimulation on Endometrial Receptivity in Women Undergoing Frozen-Thawed Embryo Transfer: A Single-Blind Prospective Randomised Controlled Trial
Authors: Shuai Zhenhong , Lian Fang , Li Pengfei , Yang Wenxiu
Published: October 2014

Objective

To evaluate the effect of transcutaneous electrical acupuncture point stimulation (TEAS) on endometrial HOXA10 protein expression and three-dimensional (3D) power Doppler ultrasound parameters as markers of endometrial receptivity in women undergoing frozen-thawed embryo transfer (FET).

Methods

A total of 68 women undergoing FET were randomised to receive TEAS or mock TEAS at acupuncture points CV3, CV4 and SP6 and Zigong bilaterally. Both groups had six sessions per cycle for three menstrual cycles prior to the scheduled FET. Each session lasted 30 min and was repeated every other day. 3D power Doppler ultrasound parameters, HOXA10 protein expression and rates of embryo implantation, clinical pregnancy and live birth were compared.

Results

There were no significant differences between the two groups in endometrial thickness or endometrial volume. The ultrasonographic endometrial triple-line pattern was present more often in the TEAS group (p=0.002). The TEAS group had a greater endometrial and subendometrial vascularisation index (VI) than the mock TEAS group (p=0.001 and p<0.001, respectively) on 3D ultrasound and increased endometrial HOXA10 expression (p=0.001) immediately prior to FET. Subsequently, the rates of embryo implantation, clinical pregnancy and live birth rates were all higher in the TEAS group than in the mock TEAS group (p=0.024, p=0.038 and p=0.033, respectively).

Conclusions

In patients undergoing FET, TEAS may have beneficial effects on endometrial HOXA10 expression and ultrasound markers of endometrial receptivity. These findings may explain the improvement in clinical outcome of FET associated with the use of TEAS.

Trial Registration Number

ChiCTR-TRC-14004448.
Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders: protocol for a network meta-analysis of randomised trials
Authors: Pagsberg A K , Tarp S , Glintborg D , Stenstrøm A D , Fink-Jensen A , Correll C U , Christensen R
Published: October 2014

Introduction

Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative effectiveness studies in children and adolescents are limited in number and size, and only a few meta-analyses based on conventional methodologies have been conducted.

Methods and analyses

We will conduct a network meta-analysis of all randomised controlled trials (RCTs) that evaluate antipsychotic therapies for EOS to determine which compounds are efficacious, and to determine the relative efficacy and safety of these treatments when compared in a network meta-analysis.

Unlike a contrast-based (standard) meta-analysis approach, an arm-based network meta-analysis enables statistical inference from combining both direct and indirect comparisons within anempirical Bayesframework. We will acquire eligible studies through a systematic search of MEDLINE, the Cochrane Central Registry of Controlled Trials, Clinicaltrials.gov and Centre for Reviews and Dissemination databases. Eligible studies should randomly allocate children and adolescents presenting with schizophrenia or a related non-affective psychotic condition to an intervention group or to a control group. Two reviewers will—independently and in duplicate—screen titles and abstracts, complete full text reviews to determine eligibility, and subsequently perform data abstraction and assess risk of bias of eligible trials. We will conduct meta-analyses to establish the effect of all reported therapies on patient-relevant efficacy and safety outcomes when possible.

Ethics and dissemination

No formal ethical procedures regarding informed consent are required as no primary data collection is undertaken. The review will help facilitate evidence-based management, identify key areas for future research, and provide a framework for conducting large systematic reviews combining direct and indirect comparisons. The study will be disseminated by peer-reviewed publication and conference presentation.

Trial registration number

PROSPERO CRD42013006676.
Validity and accuracy of maternal tactile assessment for fever in under-five children in North Central Nigeria: a cross-sectional study
Authors: Abdulkadir Mohammed Baba , Johnson Wahab Babatunde Rotimi , Ibraheem Rasheedah Mobolaji
Published: October 2014

Objectives

This study seeks to determine not only the reliability of parental touch in detecting fever as compared to rectal thermometry in under-five children, but also the sociodemographic factors that may predict its reliability.

Setting

The study was carried out in the Emergency Paediatric Unit of a tertiary hospital in North Central Nigeria.

Participants

409 children aged less than 5 years with a history of fever in the 48 h prior to presentation and their mothers were recruited consecutively. All the children recruited completed the study. Children with clinical parameters suggestive of shock, and those who were too ill, were excluded from the study.

Primary and secondary outcome measures

The primary outcome was the proportion of mothers who could accurately predict if their child was febrile or not (defined by rectal temperature) using tactile assessment only. Secondary outcomes were the validity and accuracy of touch in detecting fever and factors related to its accuracy.

Results

About 85% of the children were febrile using rectal thermometry. The sensitivity, specificity, positive predictive and negative predictive values for touch as a screening tool were 63%, 54%, 88.3% and 21%, respectively. High maternal socioeconomic status and low maternal age influenced positively the accuracy of touch in correctly determining the presence or absence of fever.

Conclusions

This study has shown that tactile assessment of temperature is not reliable and that absence of fever in a previously febrile child should be confirmed by objective methods of temperature measurement.
Finding your Way in the Fog
Authors: Vaquero Luis M. , Rodero-Merino Luis
Published: October 2014

The cloud is migrating to the edge of the network, where routers themselves may become the virtualisation infrastructure, in an evolution labelled as "the fog". However, many other complementary technologies are reaching a high level of maturity. Their interplay may dramatically shift the information and communication technology landscape in the following years, bringing separate technologies into a common ground. This paper offers a comprehensive definition of the fog, comprehending technologies as diverse as cloud, sensor networks, peer-to-peer networks, network virtualisation functions or configuration management techniques. We highlight the main challenges faced by this potentially breakthrough technology amalgamation.
ROCK-dependent ATP5D modulation contributes to the protection of notoginsenoside NR1 against ischemia-reperfusion-induced myocardial injury
Authors: He Ke , Yan Li , Pan Chun-Shui , Liu Yu-Ying , Cui Yuan-Chen , Hu Bai-He , Chang Xin , Li Quan , Sun Kai , Mao Xiao-Wei , Fan Jing-Yu , Han Jing-Yan
Published: October 2014

Cardiac ischemia-reperfusion (I/R) injury remains a challenge for clinicians, which initiates with energy metabolism disorder. The present study was designed to investigate the protective effect of notoginsenoside R1 (NR1) on I/R-induced cardiac injury and underlying mechanism. Male Sprague-Dawley rats were subjected to 30-min occlusion of the left coronary anterior descending artery followed by reperfusion with or without NR1 pretreatment (5 mg·kg−1·h−1). In vitro, H9c2 cells were cultured under oxygen and glucose deprivation/reoxygenation conditions after NR1 (0.1 mM), Rho kinase (ROCK) inhibitor Y-27632 (10 μM), or RhoA/ROCK activator U-46619 (10 nM) administration. Myocardial infarct size, myocardial histology, and cardiac function were evaluated. Myofibril and mitochondria morphology were observed by transmission electron microscopy. F-actin and apoptosis were determined by immunofluorescence and TUNEL staining. ATP and AMP content were assessed by ELISA. Phosphorylated-AMP-activated protein kinase, ATP synthase subunits, apoptosis-related molecules, and the level and activity of ROCK were determined by Western blot analysis. We found that NR1 pretreatment ameliorated myocardial infarction, histological injury, and cardiac function induced by I/R. Furthermore, similar to the effect of Y-27632, NR1 improved H9c2 cell viability, maintained actin skeleton and mitochondria morphology, and attenuated apoptosis induced by oxygen and glucose deprivation/reoxygenation. Importantly, NR1 prevented energy abnormity, inhibited the expression and activation of ROCK, and restored the expression of the mitochondrial ATP synthase δ-subunit both in vivo and in vitro, whereas U-46619 suppressed the effect of NR1. These results prove NR1 as an agent able to prevent I/R-induced energy metabolism disorder via inhibiting ROCK and enhancing mitochondrial ATP synthase δ-subunits, which at least partially contributes to its protection against cardiac I/R injury.
Distinct temporal phases of microvascular rarefaction in skeletal muscle of obese Zucker rats
Authors: Frisbee Jefferson C. , Goodwill Adam G. , Frisbee Stephanie J. , Butcher Joshua T. , Brock Robert W. , Olfert I. Mark , DeVallance Evan R. , Chantler Paul D.
Published: October 2014

Evolution of metabolic syndrome is associated with a progressive reduction in skeletal muscle microvessel density, known as rarefaction. Although contributing to impairments to mass transport and exchange, the temporal development of rarefaction and the contributing mechanisms that lead to microvessel loss are both unclear and critical areas for investigation. Although previous work suggests that rarefaction severity in obese Zucker rats (OZR) is predicted by the chronic loss of vascular nitric oxide (NO) bioavailability, we have determined that this hides a biphasic development of rarefaction, with both early and late components. Although the total extent of rarefaction was well predicted by the loss in NO bioavailability, the early pulse of rarefaction developed before a loss of NO bioavailability and was associated with altered venular function (increased leukocyte adhesion/rolling), and early elevation in oxidant stress, TNF-α levels, and the vascular production of thromboxane A2 (TxA2). Chronic inhibition of TNF-α blunted the severity of rarefaction and also reduced vascular oxidant stress and TxA2 production. Chronic blockade of the actions of TxA2 also blunted rarefaction, but did not impact oxidant stress or inflammation, suggesting that TxA2 is a downstream outcome of elevated reactive oxygen species and inflammation. If chronic blockade of TxA2 is terminated, microvascular rarefaction in OZR skeletal muscle resumes, but at a reduced rate despite low NO bioavailability. These results suggest that therapeutic interventions against inflammation and TxA2 under conditions where metabolic syndrome severity is moderate or mild may prevent the development of a condition of accelerated microvessel loss with metabolic syndrome.
Animal models of bronchopulmonary dysplasia. The term mouse models
Authors: Berger Jessica , Bhandari Vineet
Published: October 2014

The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante- and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.
Animal models of bronchopulmonary dysplasia. The term rat models
Authors: O'Reilly Megan , Thébaud Bernard
Published: October 2014

Bronchopulmonary dysplasia (BPD) is the chronic lung disease of prematurity that affects very preterm infants. Although advances in perinatal care have enabled the survival of infants born as early as 23–24 wk of gestation, the challenge of promoting lung growth while protecting the ever more immature lung from injury is now bigger. Consequently, BPD remains one of the most common complications of extreme prematurity and still lacks specific treatments. Progress in our understanding of BPD and the potential of developing therapeutic strategies have arisen from large (baboons, sheep, and pigs) and small (rabbits, rats, and mice) animal models. This review focuses specifically on the use of the rat to model BPD and summarizes how the model is used in various research studies and the advantages and limitations of this particular model, and it highlights recent therapeutic advances in BPD by using this rat model.
Patient-Derived Ovarian Tumor Xenografts Recapitulate Human Clinicopathology and Genetic Alterations
Authors: Ricci Francesca , Bizzaro Francesca , Cesca Marta , Guffanti Federica , Ganzinelli Monica , Decio Alessandra , Ghilardi Carmen , Perego Patrizia , Fruscio Robert , Buda Alessandro , Milani Rodolfo , Ostano Paola , Chiorino Giovanna , Bani Maria Rosa , Damia Giovanna , Giavazzi Raffaella
Published: October 2014

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. On the basis of its histopathology and molecular-genomic changes, ovarian cancer has been divided into subtypes, each with distinct biology and outcome. The aim of this study was to develop a panel of patient-derived EOC xenografts that recapitulate the molecular and biologic heterogeneity of human ovarian cancer. Thirty-four EOC xenografts were successfully established, either subcutaneously or intraperitoneally, in nude mice. The xenografts were histologically similar to the corresponding patient tumor and comprised all the major ovarian cancer subtypes. After orthotopic transplantation in the bursa of the mouse ovary, they disseminate into the organs of the peritoneal cavity and produce ascites, typical of ovarian cancer. Gene expression analysis and mutation status indicated a high degree of similarity with the original patient and discriminate different subsets of xenografts. They were very responsive, responsive, and resistant to cisplatin, resembling the clinical situation in ovarian cancer. This panel of patient-derived EOC xenografts that recapitulate the recently type I and type II classification serves to study the biology of ovarian cancer, identify tumor-specific molecular markers, and develop novel treatment modalities. Cancer Res; 74(23); 6980–90. ©2014 AACR.
Molecular Modulation of Estrogen-Induced Apoptosis by Synthetic Progestins in Hormone Replacement Therapy: An Insight into the Women's Health Initiative Study
Authors: Sweeney Elizabeth E. , Fan Ping , Jordan V. Craig
Published: October 2014

Hormone replacement therapy (HRT) is widely used to manage menopausal symptoms in women and can be comprised of an estrogen alone or an estrogen combined with a progestin. The Women's Health Initiative demonstrated in their randomized trials that estrogen alone HRT decreases the risk of breast cancer in postmenopausal women, whereas combined estrogen plus a progestin (medroxyprogesterone acetate, MPA) HRT increases this risk. Long-term estrogen-deprived MCF-7:5C cells were used to model the postmenopausal breast cancer cell environment. MPA is able to modify E2-induced apoptosis in MCF-7:5C cells. MPA, similar to dexamethasone, increases glucocorticoid receptor (GR) transcriptional activity, increases SGK1, a GR target gene, and can be blocked by RU486 (an antiglucocorticoid), suggesting that it functions through the GR. Norethindrone acetate (NETA), another progestin used in HRT, acts like an estrogen at high doses, upregulating estrogen receptor target genes and generating apoptosis in MCF-7:5C cells. The data suggest that women taking HRT comprising an estrogen plus MPA may have an increased risk of breast cancer due to MPA acting as a glucocorticoid and blunting E2-induced apoptosis in this environment. Therefore, perhaps other approved progestins (e.g., NETA) should be considered as alternatives to MPA. Cancer Res; 74(23); 7060–8. ©2014 AACR.
Chemotherapeutic Agents Subvert Tumor Immunity by Generating Agonists of Platelet-Activating Factor
Authors: Sahu Ravi P. , Ocana Jesus A. , Harrison Kathleen A. , Ferracini Matheus , Touloukian Christopher E. , Al-Hassani Mohammed , Sun Louis , Loesch Mathew , Murphy Robert C. , Althouse Sandra K. , Perkins Susan M. , Speicher Paul J. , Tyler Douglas S. , Konger Raymond L. , Travers Jeffrey B.
Published: October 2014

Oxidative stress suppresses host immunity by generating oxidized lipid agonists of the platelet-activating factor receptor (PAF-R). Because many classical chemotherapeutic drugs induce reactive oxygen species (ROS), we investigated whether these drugs might subvert host immunity by activating PAF-R. Here, we show that PAF-R agonists are produced in melanoma cells by chemotherapy that is administered in vitro, in vivo, or in human subjects. Structural characterization of the PAF-R agonists induced revealed multiple oxidized glycerophosphocholines that are generated nonenzymatically. In a murine model of melanoma, chemotherapeutic administration could augment tumor growth by a PAF-R–dependent process that could be blocked by treatment with antioxidants or COX-2 inhibitors or by depletion of regulatory T cells. Our findings reveal how PAF-R agonists induced by chemotherapy treatment can promote treatment failure. Furthermore, they offer new insights into how to improve the efficacy of chemotherapy by blocking its heretofore unknown impact on PAF-R activation. Cancer Res; 74(23); 7069–78. ©2014 AACR.
Therapeutic Strategies Utilized in the Setting of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Yu Helena A. , Riely Gregory J. , Lovly Christine M.
Published: October 2014

Patients with EGFR-mutant lung cancer derive significant therapeutic benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). Unfortunately, acquired resistance is an inevitable consequence of this treatment strategy, with a broad variety of resistance mechanisms including acquired EGFR mutations (e.g., T790M) and activation of bypass signaling pathways, such as MET and HER2. Several therapeutic strategies hypothesized to delay or overcome resistance have been tested in clinical trials, including “next-generation” EGFR TKIs and rational combinations of targeted agents. However, to date, there are no FDA-approved therapies for patients with acquired resistance to first-line EGFR TKI therapy. There remains a critical need for more effective and better tailored treatments in this setting to match treatments to the individual patient and specific resistance mechanism at hand. In this review, we discuss known mechanisms of resistance to first-line EGFR TKI therapy and describe previous and ongoing strategies to overcome resistance. Clin Cancer Res; 20(23); 5898–907. ©2014 AACR.
Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma
Authors: Pickering Curtis R. , Zhou Jane H. , Lee J. Jack , Drummond Jennifer A. , Peng S. Andrew , Saade Rami E. , Tsai Kenneth Y. , Curry Jonathan L. , Tetzlaff Michael T. , Lai Stephen Y. , Yu Jun , Muzny Donna M. , Doddapaneni Harshavardhan , Shinbrot Eve , Covington Kyle R. , Zhang Jianhua , Seth Sahil , Caulin Carlos , Clayman Gary L. , El-Naggar Adel K. , Gibbs Richard A. , Weber Randal S. , Myers Jeffrey N. , Wheeler David A. , Frederick Mitchell J.
Published: October 2014

Purpose: Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal disease. Very little is currently known about the mutations that drive aggressive cSCC.

Experimental Design: Whole-exome sequencing was performed on 39 cases of aggressive cSCC to identify driver genes and novel therapeutic targets. Significantly, mutated genes were identified with MutSig or complementary methods developed to specifically identify candidate tumor suppressors based upon their inactivating mutation bias.

Results: Despite the very high-mutational background caused by UV exposure, 23 candidate drivers were identified, including the well-known cancer-associated genes TP53, CDKN2A, NOTCH1, AJUBA, HRAS, CASP8, FAT1, and KMT2C (MLL3). Three novel candidate tumor suppressors with putative links to cancer or differentiation, NOTCH2, PARD3, and RASA1, were also identified as possible drivers in cSCC. KMT2C mutations were associated with poor outcome and increased bone invasion.

Conclusions: The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor-suppressor genes. These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC. Clin Cancer Res; 20(24); 6582–92. ©2014 AACR.
A Tale of Two Receptors: Insulin and Insulin-Like Growth Factor Signaling in Cancer
Authors: Yee Douglas
Published: October 2014

Inhibition of the type I IGF receptor (IGF1R) has been the focus of numerous clinical trials. Two reports in this issue describe the results of phase I trials of an IGF1R tyrosine kinase inhibitor OSI-906. This commentary will describe the complex endocrine changes induced by these types of agents. Clin Cancer Res; 21(4); 667–9. ©2014 AACR.

See related articles by Jones et al., p. 693, and Puzanov et al., p. 701
Clinically Relevant microRNAs in Ovarian Cancer
Authors: Zhang Shu , Lu Zhen , Unruh Anna K. , Ivan Cristina , Baggerly Keith A. , Calin George A. , Li Zongfang , Bast Robert C. , Le Xiao-Feng
Published: October 2014

microRNAs (miRNAs/miRs) belong to a class of small noncoding RNAs that can negatively regulate messenger RNA (mRNA) expression of target genes. miRNAs are involved in multiple aspects of ovarian cancer cell dysfunction and the phenotype of ovarian cancer cells can be modified by targeting miRNA expression. miRNA profiling has detected a number of candidate miRNAs with the potential to regulate many important biologic functions in ovarian cancer, but their role still needs to be clarified, given the remarkable heterogeneity among ovarian cancers and the context-dependent role of miRNAs. This review summarizes the data collected from The Cancer Genome Atlas (TCGA) and several other genome-wide projects to identify dysregulated miRNAs in ovarian cancers. Copy number variations (CNVs), epigenetic alterations, and oncogenic mutations are also discussed that affect miRNA levels in ovarian disease. Emphasis is given to the role of particular miRNAs in altering expression of genes in human ovarian cancers with the potential to provide diagnostic, prognostic, and therapeutic targets. Particular attention has been given to TP53, BRCA1/2, CA125 (MUC16), HE4 (WFDC2), and imprinted genes such as ARHI (DIRAS3). A better understanding of the abnormalities in miRNA expression and downstream transcriptional and biologic consequences will provide leads for more effective biomarkers and translational approaches in the management of ovarian cancer. Mol Cancer Res; 13(3); 393–401. ©2014 AACR.
Trends in Early Aspirin Use Among Patients With Acute Myocardial Infarction in China, 2001–2011: The China PEACE‐Retrospective AMI Study
Authors: Gao Yan , Masoudi Frederick A. , Hu Shuang , Li Jing , Zhang Haibo , Li Xi , Desai Nihar R. , Krumholz Harlan M. , Jiang Lixin ,   the China PEACE Collaborative Group
Published: October 2014

Background

Aspirin is an effective, safe, and inexpensive early treatment of acute myocardial infarction (
AMI
) with few barriers to administration, even in countries with limited healthcare resources. However, the rates and recent trends of aspirin use for the early treatment of
AMI
in China are unknown.

Methods and Results

Using data from the China Patient‐centered Evaluative Assessment of Cardiac Events Retrospective Study of Acute Myocardial Infarction (China
PEACE
‐Retrospective
AMI
Study), we identified a cohort of 14 041 patients with
AMI
eligible for early aspirin therapy. Early use of aspirin for
AMI
increased over time (78.4% in 2001, 86.5% in 2006, and 90.0% in 2011). However, about 15% of hospitals had a rate of use of <80% in 2011. Treatment was less likely in patients who were older, presented with cardiogenic shock at admission, presented without chest discomfort, had a final diagnosis of non‐
ST
‐segment elevation acute myocardial infarction, or did not receive reperfusion therapy. Hospitalization in rural regions was also associated with aspirin underuse.

Conclusions

Despite improvements in early use of aspirin for
AMI
in China, there remains marked variation in practice and opportunities for improvement that are concentrated in some hospitals and patient groups.

Clinical Trial Registration

URL:
ClinicalTrials.gov
Unique identifier: NCT01624883.
The making of ‘professional amateurs’
Authors: Andreassen Tone Alm , Breit Eric , Legard Sveinung
Published: October 2014

The aim of this article is, through empirical material from Norway, to grasp a particular form of non-profit professionalization spurred by the incorporation of policies of service user involvement in health care and in social services. By drawing on perspectives from the research on professionalization, our ambition is to increase the understanding of the nature of this form of professionalization, how it differs from other kinds of professionalization in the non-profit sector and why it achieves its distinctive features. We denote the professionalization of service users’ work as representatives, as the making of ‘professional amateurs’ to capture its paradoxical nature – that while the process of professionalization resembles occupational professionalization, the voluntary workers who are becoming professionalized are still amateurs. It is professionalization in the form of increasing the competence of the voluntary workers, not professionalization through transforming voluntary work tasks into occupations and paid employment. It is a form of competence fundamentally resting on personal experience with the issues with which the work is concerned, not a competence to be achieved solely through education and professional training.
From school to fitting work
Authors: Levels Mark , van der Velden Rolf , Di Stasio Valentina
Published: October 2014

Although optimal labour market allocation of school leavers benefits individuals, employers and societies, a substantial part of European school leavers do not find a job that matches their field or level of education. This paper explores the extent to which horizontal and vertical education-to-job matches of European school leavers from secondary education is associated with the level of stratification, standardization, and the level of vocational orientation and institutional linkages of education systems. We combine notions of signalling theory, human capital theory and job matching theory to formulate hypotheses about how education systems affect horizontal and vertical education-to-job matches. We use micro-data on 30,805 school leavers in 20 European countries from the 2009 Ad Hoc Module of the European Labour Force Survey and data on system characteristics. Using multi-level logistic regression, we show that the level of stratification of secondary education is associated with better vertical job matches. We also find that the positive relation between being vocationally trained and education-to-job matches is stronger in systems with stronger institutional linkages. The positive relation between being vocationally trained and vertical job matches is less strong in more vocational oriented systems. Theoretical and practical implications are discussed.
Dignity and Dreams
Authors: Sykes Jennifer , Križ Katrin , Edin Kathryn , Halpern-Meekin Sarah
Published: October 2014

Money has meaning that shapes its uses and social significance, including the monies low-income families draw on for survival: wages, welfare, and the Earned Income Tax Credit (EITC). This study, based on in-depth interviews with 115 low-wage EITC recipients, reveals the EITC is an unusual type of government transfer. Recipients of the EITC say they value the debt relief this government benefit brings. However, they also perceive it as a just reward for work, which legitimizes a temporary increase in consumption. Furthermore, unlike other means-tested government transfers, the credit is seen as a springboard for upward mobility. Thus, by conferring dignity and spurring dreams, the EITC enhances feelings of citizenship and social inclusion.
Tracheal Size Variability Is Associated With Sex
Authors: Karmakar Arunabha , Pate Mariah B. , Solowski Nancy L. , Postma Gregory N. , Weinberger Paul M.
Published: October 2014

Purpose:

Whereas selection of endotracheal tube (ETT) size in pediatric patients benefits from predictive nomograms, adult ETT sizing is relatively arbitrary. We sought to determine associations between cervical tracheal cross-sectional area (CTCSA) and clinical variables.

Methods:

One hundred thirty-two consecutive patients undergoing noncontrasted chest computed tomography (CT) at a single tertiary care institution from January 2010 to June 2011 were reviewed. Patients with improper CT technique, endotracheal intubation, and pulmonary/tracheal pathology were excluded. Tracheal luminal diameters in anteroposterior (D1) and transverse (D2) were measured 2 cm inferior to the cricoid and used to determine CTCSA = π*D1*D2*¼. The demographic variables of age, height, weight, and body mass index (BMI) were tested for association with CTCSA by Spearman correlation. Wilcoxon rank-sum test was used to compare CTCSA by race and sex. Multivariate linear regression was performed including all clinical variables.

Results:

There were 91 patients who met inclusion criteria. There was no correlation between age, weight, or BMI and CTCSA. There was a significant positive correlation between patient height and CTCSA ( P = .001, R = 0.35); however, this was confounded by sex. Female patients had significantly smaller CTCSA (mean = 241 mm2) compared to male patients (mean = 349 mm2, P < .001). Multivariate linear regression stratified by sex revealed that height is correlated with CTCSA only in males ( P = .028). Males also had more variability in CTCSA (SD 118.6) compared to females (SD 65.5).

Conclusion:

Our data suggest that selection of ETT size in male patients should include height as a predictive factor. For female patients, it may be appropriate to select a uniformly smaller diameter ETT size.
Sexual Harassment in Middle and High School Children and Effects on Physical and Mental Health
Authors: Eom Elizabeth , Restaino Stephen , Perkins Amy M. , Neveln Nicole , Harrington John W.
Published: October 2014

Sexual harassment can be physical interaction and touching, as well as, psychological, environmental, or via Internet and text messaging. An online survey in an urban clinic asked children, aged 12 to 18 years the following: demographic data, height and weight, chronic medical conditions, healthcare use, questions concerning sexual harassment—witnessed and exposure, and finally questions from the Pediatric Symptom Checklist (PSC-35). Overall, 124 of 210 (59%) of the 12- to 18-year-olds surveyed had experienced sexual harassment, with the predominance being female 69% (80/116) versus 48% (49/92) male. Participants who had experienced sexual harassment were significantly more likely to score positive for psychological impairment than those who had not experienced sexual harassment (chi-square test P < .001; odds ratio: 4.7 (95% confidence interval, 1.9-11.8). There was a borderline significant association between elevated body mass index and having experienced sexual harassment (2-sample t test P = .08). Sexual harassment has a direct correlation to psychological impairment in adolescents, especially females.