bluuebunny/crossref_metadata_2025 huggingface dataset:
Metatranscriptomic Analysis of Larval Guts from Field-Collected and Laboratory-Reared Spodoptera frugiperda from the South American Subtropical Region
Authors: McCarthy Christina B. , Cabrera Natalia A. , Virla Eduardo G.
Published: July 2015

This is the first study to report a high-throughput approach integrating gene expression data from
Spodoptera frugiperda
guts and their associated metatranscriptomes. Our datasets provide information on the potential effects of environmental conditions on the expression profile of
S. frugiperda
larval guts, their associated metatranscriptome, and putative interactions between them.
Complete Genome Sequence of an Atypical Dengue Virus Serotype 2 Lineage Isolated in Brazil
Authors: Salvador Felipe Scassi , Amorim Jaime Henrique , Alves Rubens Prince Santos , Pereira Sara A. , Ferreira Luis Carlos Souza , Romano Camila Malta
Published: July 2015

Here, we report the complete polyprotein sequence of a dengue virus 2 strain isolated in Brazil. This virus belongs to the American genotype and has the ability to cause neurovirulence in immunocompetent adult mice. The data presented here may help understand the genetic determinants responsible for neurovirulence.
Complete Genome Sequence of a Phenanthrene Degrader,
Mycobacterium
sp. Strain EPa45 (NBRC 110737), Isolated from a Phenanthrene-Degrading Consortium
Authors: Kato Hiromi , Ogawa Natsumi , Ohtsubo Yoshiyuki , Oshima Kenshiro , Toyoda Atsushi , Mori Hiroshi , Nagata Yuji , Kurokawa Ken , Hattori Masahira , Fujiyama Asao , Tsuda Masataka
Published: July 2015

A phenanthrene degrader,
Mycobacterium
sp. EPa45, was isolated from a phenanthrene-degrading consortium. Here, we report the complete genome sequence of EPa45, which has a 6.2-Mb single circular chromosome. We propose a phenanthrene degradation pathway in EPa45 based on the complete genome sequence.
De Novo
Whole-Genome Sequence and Annotation of a
Leishmania
Strain Isolated from a Case of Post-Kala-Azar Dermal Leishmaniasis
Authors: Gupta Anil Kumar , Srivastava Saumya , Singh Amit , Singh Sarman
Published: July 2015

The pathogenesis of post-kala-azar dermal leishmaniasis (PKDL) is complex. Only 5 to 10% of kala-azar patients develop this dermal complication, and it is not known whether this is due to changes in the parasite genome or some host factors. Here, we report the whole-genome sequence and annotated genes of the whole genome of the PKDL strain.
Draft Genome Sequence of a Novel Nicotine-Degrading Bacterium, Pseudomonas plecoglossicida TND35
Authors: Raman Gurusamy , Sakthivel Natarajan , Park SeonJoo
Published: July 2015

Pseudomonas plecoglossicida
TND35 is a potent nicotine-degrading bacterium. The draft genome sequence of strain TND35 contains 6,209,227 bp, 5,511 coding genes, and a G+C content of 62.3%. It encompasses genes related to catabolism of nicotine,
N
-heterocyclic aromatic compounds, heavy metal degradation, and butanol biosynthesis.
Anaemia and related nutrient deficiencies after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis
Authors: Weng Ting-Chia , Chang Chia-Hsuin , Dong Yaa-Hui , Chang Yi-Cheng , Chuang Lee-Ming
Published: July 2015

Objective

To obtain a pooled risk estimate on the long-term impact of anaemia and related nutritional deficiencies in patients receiving Roux-en-Y gastric bypass (RYGB) surgery.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, EMBASE and Cochrane databases were searched to identify English reports published before 16 May 2014.

Eligibility criteria

Articles with case numbers >100, follow-up period >12 months, and complete data from both before and after surgery were selected. Outcomes of interest were changes in baseline measurements of proportion of patients with anaemia, by haemoglobin, haematocrit, ferritin, iron, vitamin B12and folate levels.

Data collection and analysis

Two reviewers independently reviewed data and selected six prospective and nine retrospective studies with a total of 5909 patients. A random effect model with inverse variance weighting was used to calculate summary estimates of outcomes at 6, 12, 24 and 36 months postoperatively.

Results

Proportion of patients with anaemia was 12.2% at baseline, which, respectively, increased to 20.9% and 25.9% at 12 and 24 months follow-up, consistent with decreases in haemoglobin and haematocrit levels. Although the serum iron level did not change substantially after surgery, the frequency of patients with ferritin deficiency increased from 7.9% at baseline to 13.4% and 23.0% at 12 and 24 months, respectively, postoperation. Vitamin B12deficiency increased from 2.3% at baseline to 6.5% at 12 months after surgery in those subjects receiving RYGB. There was no obvious increase in folate deficiency.

Conclusions

RYGB surgery is associated with an increased risk of anaemia and deficiencies of iron and vitamin B12, but not folate. Ferritin is more sensitive when serum iron level is within normal range.
Alcohol detoxification in Ysbyty Gwynedd: Two small sips or one big gulp? Two-step screening more reliable for identification of alcohol dependency syndrome at risk of delirium tremens for routine care
Authors: Salman Muhammad , Subbe Christian
Published: July 2015

Compliance with pathways for hospitalised patients with alcohol dependency syndrome is often poor. A pathway for recognition and treatment of alcohol dependency was redesigned as part of a 12 month service improvement project in the acute medical unit using plan, do, study, act (PDSA) cycles.

A needs assessment was undertaken: Audit data from 2013 showed over-prescription of chlordiazepoxide for detoxification treatment (DT) leading to prolonged hospital admissions with an average length of stay of 5.5 days in 2012/2013.

Acceptability of screening tools was tested: Common screening tools (CEWA, AUDIT) were rejected by junior doctors due to the high number of questions as too cumbersome for routine practice. Compliance with usage in random samples over a three month period was persistently <10%. Testing of an abbreviated AUDIT questionnaire with only two questions and a specified threshold showed a AUROC of 1 (p<0.001 for correct identification).

The screening tool was implemented in several PDSAs cycles. After the final cycle a random sample of 100 patients was reviewed for pathway compliance over a three months period. Eighty-six patients were screened with the two-question tool of these 18 were identified as possible risk. Of these 16 patients had the full AUDIT questionnaire, only eight with elevated values were started on DT. Overall compliance with the pathway increased to 84%.
Specialist palliative care improves the quality of life in advanced neurodegenerative disorders: NE-PAL, a pilot randomised controlled study
Authors: Veronese Simone , Gallo G , Valle A , Cugno C , Chiò A , Calvo A , Cavalla P , Zibetti M , Rivoiro C , Oliver D J
Published: July 2015

Background

This study analysed the impact on palliative care outcomes of a new specialist palliative care service for patients severely affected by amyotrophic lateral sclerosis (ALS/MND), multiple sclerosis, Parkinson's disease and related disorders (multiple system atrophy progressive supranuclear palsy, MSA-PSP).

Methods

The design followed the Medical Research Council Framework for the evaluation of complex interventions. A phase II randomised controlled trial (RCT) was undertaken comparing an immediate referral to the service (FT, fast track) to a 16-week wait (standard track (ST), standard best practice) using a parallel arm design. The main outcome measures were Quality of Life (measured with Schedule for the Evaluation of Individual Quality of Life Direct Weight, SEIQoL-DW) and burden of the carers (Caregivers Burden Inventory, CBI), with secondary outcomes of symptoms, psychosocial and spiritual issues.

Results

50 patients severely affected by neurodegenerative conditions and their informal family carers were randomised: 25 FT, 25 ST. At baseline (T0), there were no differences between groups. 4 patients died during the follow-up (2 FT, 2 ST) and 2 FT patients dropped out before the end of the study. After 16 weeks (T1), FT participants scored significant improvement in the SEIQoL-DW index, pain dyspnoea sleep disturbance and bowel symptoms.

Conclusions

This exploratory RCT provides evidence that no harm was experienced by SPCS for patients severely affected by neurodegenerative disorders. There was an improvement in quality of life and physical symptoms for neurological patients in palliative care. Caregiver burden was not affected by the service.
Why don't end-of-life conversations go viral? A review of videos on YouTube
Authors: Mitchell Imogen A , Schuster Anne L R , Lynch Thomas , Smith Katherine Clegg , Bridges John F P , Aslakson Rebecca A
Published: July 2015

Objective

To identify videos on YouTube concerning advance care planning (ACP) and synthesise existing video content and style elements.

Methods

Informed by stakeholder engagement, two researchers searched YouTube for ACP videos using predefined search terms and snowballing techniques. Videos identified were reviewed and deemed ineligible for analysis if they: targeted healthcare professionals; contained irrelevant content; focused on viewers under the age of 18; were longer than 7 min in duration; received fewer than 150 views; were in a language other than English; or were a duplicate version. For each video, two investigators independently extracted general information as well as video content and stylistic characteristics.

Results

The YouTube search identified 23 100 videos with 213 retrieved for assessment and 42 meeting eligibility criteria. The majority of videos had been posted to YouTube since 2010 and produced by organisations in the USA (71%). Viewership ranged from 171 to 10 642. Most videos used a documentary style and featured healthcare providers (60%) rather than patients (19%) or families (45%). A minority of videos (29%) used upbeat or hopeful music. The videos frequently focused on completing legal medical documents (86%).

Conclusions

None of the ACP videos on YouTube went viral and a relatively small number of them contained elements endorsed by stakeholders. In emphasising the completion of legal medical documents, videos may have failed to support more meaningful ACP. Further research is needed to understand the features of videos that will engage patients and the wider community with ACP and palliative and end-of-life care conversations.
Body size and body composition: a comparison of children in India and the UK through infancy and early childhood
Authors: D'Angelo S , Yajnik C S , Kumaran K , Joglekar C , Lubree H , Crozier S R , Godfrey K M , Robinson S M , Fall C H D , Inskip H M
Published: July 2015

Background

Indian babies are characterised by the ‘thin-fat phenotype’ which comprises a ‘muscle-thin but adipose’ body composition compared with European babies. This body phenotype is of concern because it is associated with an increased risk of diabetes and cardiovascular disease. We examined whether the ‘thin-fat phenotype’ persists through early childhood, comparing Indian children with white Caucasians in the UK at birth, infancy and childhood, using comparable measurement protocols.

Methods

We used data from two cohorts, the Pune Maternal Nutrition Study (N=631) and the Southampton Women's Survey (N=2643). Measurements of weight, head circumference, mid-upper arm circumference, height, triceps and subscapular skinfold thickness were compared at birth, 1, 2, 3 and 6 years of age. SD scores were generated for the Pune children, using the Southampton children as a reference. Generalised estimating equations were used to examine the changes in SD scores across the children's ages.

Results

The Indian children were smaller at birth in all body measurements than the Southampton children and became relatively even smaller from birth to 2 years, before ‘catching up’ to some extent at 3 years, and more so by 6 years. The deficit for both skinfolds was markedly less than for other measurements at all ages; triceps skinfold showed the least difference between the two cohorts at birth, and subscapular skinfold at all ages after birth.

Conclusions

The ‘thin-fat phenotype’ previously found in Indian newborns, remains through infancy and early childhood. Despite being shorter and lighter than UK children, Indian children are relatively adipose.
Maternal mental health and risk of child protection involvement: mental health diagnoses associated with increased risk
Authors: O'Donnell Melissa , Maclean Miriam J , Sims Scott , Morgan Vera A , Leonard Helen , Stanley Fiona J
Published: July 2015

Background

Previous research shows that maternal mental illness is an important risk factor for child maltreatment. This study aims to quantify the relationship between maternal mental health and risk of child maltreatment according to the different types of mental health diagnoses.

Methods

The study used a retrospective cohort of children born in Western Australia between 1990 and 2005, with deidentified linked data from routine health and child protection collections.

Results

Nearly 1 in 10 children (9.2%) of mothers with a prior mental health contact had a maltreatment allegation. Alternatively, almost half the children with a maltreatment allegation had a mother with a mental health contact. After adjusting for other risk factors, a history of mental health contacts was associated with a more than doubled risk of allegations (HR=2.64, 95% CI 2.50 to 2.80). Overall, all mental health diagnostic groups were associated with an increased risk of allegations. The greatest risk was found for maternal intellectual disability, followed by disorders of childhood and psychological development, personality disorders, substance-related disorders, and organic disorders. Maltreatment allegations were substantiated at a slightly higher rate than for the general population.

Conclusions

Our study shows that maternal mental health is an important factor in child protection involvement. The level of risk varies across diagnostic groups. It is important that mothers with mental health issues are offered appropriate support and services. Adult mental health services should also be aware and discuss the impact of maternal mental health on the family and children's safety and well-being.
Republished: The clinical spectrum of pulmonary aspergillosis
Authors: Kosmidis Chris , Denning David W
Published: July 2015

The clinical presentation of Aspergillus lung disease is determined by the interaction between fungus and host. Invasive aspergillosis develops in severely immunocompromised patients, including those with neutropenia, and increasingly in the non-neutropenic host, including lung transplant recipients, the critically ill patients and patients on steroids. A high index of suspicion is required in patients without the classical risk factors as early presentation is usually silent and non-specific, pyrexia uncommon and timely treatment is crucial for survival. Invasive aspergillosis has also been diagnosed in normal hosts after massive exposure to fungal spores. Chronic pulmonary aspergillosis affects patients without obvious immune compromise, but with an underlying lung condition such as COPD or sarcoidosis, prior or concurrent TB or non-tuberculous mycobacterial disease. Aspergillus bronchitis may be responsible for persistent respiratory symptoms in patients with Aspergillus detected repeatedly in sputum without evidence of parenchymal Aspergillus disease, especially in patients with bronchiectasis and cystic fibrosis. Allergic bronchopulmonary aspergillosis affects patients with asthma and cystic fibrosis, and is important to recognise as permanent lung or airways damage may accrue if untreated. Changes in the classification of Aspergillus allergic lung disease have been proposed recently. Cases of extrinsic allergic alveolitis and chronic pulmonary aspergillosis have been observed after Aspergillus exposure. Asymptomatic colonisation of the respiratory tract needs close monitoring as it can lead to clinical disease especially with ongoing immunosuppression. The various syndromes should be viewed as a semicontinuous spectrum of disease and one form may evolve into another depending on the degree of ongoing immunosuppression.
Republished: Genetic investigations in childhood deafness
Authors: Parker Michael , Bitner-Glindzicz Maria
Published: July 2015

Permanent childhood sensorineural hearing loss, is one of the most common birth defects in developed countries. It is important to identify the aetiology of hearing loss for many reasons, as there may be important health surveillance implications particularly with syndromic causes. Non-syndromic sensorineural hearing loss is a highly heterogeneous genetic condition, meaning that it may be caused by any one of numerous genes, with very few phenotypic distinctions between the different genetic types. This has previously presented significant challenges for genetic testing. However, the introduction of new technologies should enable more comprehensive testing in the future, bringing significant benefits to more affected children and their families.
Three-dimensional effects in low-strain integrity testing of piles: analytical solution
Authors: Zheng Changjie , Kouretzis George P. , Ding Xuanming , Liu Hanlong , Poulos Harry G.
Published: July 2015

The interpretation of low-strain integrity tests of piles is commonly based on methods developed around the one-dimensional wave propagation theory. In reality, waves resulting from the impact of a hammer on a pile head propagate in three dimensions, and the validity of the plane-front assumption is rather questionable for cases where the size of the hammer is small relative to that of the pile. This paper presents an analytical model of the dynamic response of a pile to an impact load on its head, considering propagation of waves in both vertical and radial directions. The proposed formulation applies to a pile of finite length embedded in multilayered elastic soil, and allows for considering both shape and material pile defects, by reducing locally the radius of the pile cross section or the Young’s modulus of its material. Arithmetic examples are used to depict the effect of high-frequency interferences on the interpretation of pile integrity tests, which can only be accounted for in the three-dimensional formulation of the problem, and lead to practical suggestions for the interpretation of such tests.
Empowering Patients and Caregivers to Manage Healthcare Via Streamlined Presentation of Web Objects Selected by Modeling Learning Benefits Obtained by Similar Peers
Authors: Champaign John , Cohen Robin , Lam Disney Yan
Published: July 2015

In this article, we introduce a framework for selecting web objects (texts, videos, simulations) from a large online repository to present to patients and caregivers, in order to assist in their healthcare. Motivated by the paradigm of peer-based intelligent tutoring, we model the learning gains achieved by users when exposed to specific web objects in order to recommend those objects most likely to deliver benefit to new users. We are able to show that this streamlined presentation leads to effective knowledge gains, both through a process of simulated learning and through a user study, for the specific application of caring for children with autism. The value of our framework for peer-driven content selection of health information is emphasized through two additional roles for peers: attaching commentary to web objects and proposing subdivided objects for presentation, both of which are demonstrated to deliver effective learning gains, in simulations. In all, we are offering an opportunity for patients to navigate the deep waters of excessive online information towards effective management of healthcare, through content selection influenced by previous peer experiences.
Polyhedral AST Generation Is More Than Scanning Polyhedra
Authors: Grosser Tobias , Verdoolaege Sven , Cohen Albert
Published: July 2015

Abstract mathematical representations such as integer polyhedra have been shown to be useful to precisely analyze computational kernels and to express complex loop transformations. Such transformations rely on abstract syntax tree (AST) generators to convert the mathematical representation back to an imperative program. Such generic AST generators avoid the need to resort to transformation-specific code generators, which may be very costly or technically difficult to develop as transformations become more complex. Existing AST generators have proven their effectiveness, but they hit limitations in more complex scenarios. Specifically, (1) they do not support or may fail to generate control flow for complex transformations using piecewise schedules or mappings involving modulo arithmetic; (2) they offer limited support for the specialization of the generated code exposing compact, straightline, vectorizable kernels with high arithmetic intensity necessary to exploit the peak performance of modern hardware; (3) they offer no support for memory layout transformations; and (4) they provide insufficient control over the AST generation strategy, preventing their application to complex domain-specific optimizations.

We present a new AST generation approach that extends classical polyhedral scanning to the full generality of Presburger arithmetic, including existentially quantified variables and piecewise schedules, and introduce new optimizations for the detection of components and shifted strides. Not limiting ourselves to control flow generation, we expose functionality to generate AST expressions from arbitrary piecewise quasi-affine expressions, which enables the use of our AST generator for data-layout transformations. We complement this with support for specialization by polyhedral unrolling, user-directed versioning, and specialization of AST expressions according to the location at which they are generated, and we complete this work with fine-grained user control over the AST generation strategies used. Using this generalized idea of AST generation, we present how to implement complex domain-specific transformations without the need to write specialized code generators, but instead relying on a generic AST generator parametrized to a specific problem domain.
Identifying Opportunities for Valuable Encounters
Authors: Mayer Julia M. , Jones Quentin , Hiltz Starr Roxanne
Published: July 2015

Mobile social matching systems have the potential to transform the way we make new social ties, but only if we are able to overcome the many challenges that exist as to how systems can utilize contextual data to recommend interesting and relevant people to users and facilitate valuable encounters between strangers. This article outlines how context and mobility influence people's motivations to meet new people and presents innovative design concepts for mediating mobile encounters through context-aware social matching systems. Findings from two studies are presented. The first, a survey study (n = 117) explored the concept of contextual rarity of shared user attributes as a measure to improve desirability in mobile social matches. The second, an interview study (n = 58) explored people's motivations to meet others in various contexts. From these studies we derived a set of novel context-aware social matching concepts, including
contextual sociability and familiarity
as an indicator of opportune social context;
contextual engagement
as an indicator of opportune personal context; and
contextual rarity, oddity,
and
activity partnering
as an indicator of opportune relational context. The findings of these studies establish the importance of different contextual factors and frame the design space of context-aware social matching systems.
Model Checking Distributed Mandatory Access Control Policies
Authors: Alexander Perry , Pike Lee , Loscocco Peter , Coker George
Published: July 2015

This work examines the use of model checking techniques to verify system-level security properties of a collection of interacting virtual machines. Specifically, we examine how local access control policies implemented in individual virtual machines and a hypervisor can be shown to satisfy global access control constraints. The SAL model checker is used to model and verify a collection of stateful domains with protected resources and local MAC policies attempting to access needed resources from other domains. The model is described along with verification conditions. The need to control state-space explosion is motivated and techniques for writing theorems and limiting domains explored. Finally, analysis results are examined along with analysis complexity.
TCP Stretch Acknowledgements and Timestamps
Authors: Ding Hao , Rabinovich Michael
Published: July 2015

This paper examines several TCP characteristics and their effect on existing passive RTT measurement techniques. In particular, using packet traces from three geographically distributed vantage points, we find relatively low use of TCP timestamps and significant presence of stretch acknowledgements. While the former simply affects the applicability of some measurement techniques, the latter may in principle affect the accuracy of RTT estimation. Using these insights, we quantify implications of common methodologies for passive RTT measurement. In particular, we show that, unlike delayed TCP acknowledgement, stretch acknowledgments do not distort RTT estimations.
Lessons Learned From Using the RIPE Atlas Platform for Measurement Research
Authors: Bajpai Vaibhav , Eravuchira Steffie Jacob , Schönwälder Jürgen
Published: July 2015

We reflect upon our experience in using the RIPE Atlas platform for measurement-based research. We show how in addition to credits, control checks using rate limits are in place to ensure that the platform does not get overloaded with measurements. We show how the Autonomous System (AS)-based distribution of RIPE Atlas probes is heavily skewed which limits possibilities of measurements sourced from a specific origin-AS. We discuss the significance of probe calibration and how we leverage it to identify load issues in older hardware versions (38.6% overall as of Sep 2014) of probes. We show how performance measurement platforms (such as RIPE Atlas, SamKnows, BISmark and Dasu) can benefit from each other by demonstrating two example use-cases. We also open discussion on how RIPE Atlas deployment can be made more useful by relaying more probe metadata information back to the scientific community and by strategically deploying probes to reduce the inherent sampling bias embedded in probe-based measurement platforms.
Reduced FoxO3a expression causes low autophagy in idiopathic pulmonary fibrosis fibroblasts on collagen matrices
Authors: Im Jintaek , Hergert Polla , Nho Richard Seonghun
Published: July 2015

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal lung disease, and fibroblasts derived from patients with IPF are resistant to type I collagen matrix-induced cell death. The alteration of the PTEN-Akt axis permits IPF fibroblasts to maintain a pathological phenotype on collagen by suppressing autophagy. However, the precise underlying mechanism by which the Akt downstream molecule suppresses autophagic activity remains elusive. FoxO3a is a direct target of Akt and is implicated with the transcriptional activation of autophagy. Therefore, we investigated whether reduced FoxO3a expression causes abnormally low autophagy in IPF fibroblasts on collagen. We found that FoxO3a mRNA and protein levels are low in IPF fibroblasts, which subsequently suppresses the autophagosomal marker LC3B expression on collagen matrix. In contrast, the majority of control fibroblasts showed an increase in FoxO3a and LC3B expression at both the mRNA and protein levels. The luciferase assay confirmed that FoxO3a binds to the promoter region of LC3B and transcriptionally activates LC3B. The overexpression of wild-type FoxO3a increased LC3B mRNA and protein expression in IPF fibroblasts, whereas the dominant negative FoxO3a decreased the LC3B level in control fibroblasts. The inhibition of autophagic activity sensitized control fibroblasts to collagen matrix-induced cell death. In contrast, enhanced viability was found when autophagic function was inhibited in IPF fibroblasts. Our study showed that aberrantly low FoxO3a expression participates in reducing autophagic activity via transcriptional suppression of LC3B in IPF fibroblasts on collagen. This suggests that low autophagic activity by the alteration of FoxO3a may contribute to IPF progression.
Impact of bifurcation dual stenting on endothelial shear stress
Authors: Chen Henry Y. , Koo Bon-Kwon , Kassab Ghassan S.
Published: July 2015

Despite advances in percutaneous coronary interventions and the introduction of drug eluding stents, in-stent restenosis and stent thrombosis remain a clinically significant problem for bifurcations. The aim of this study is to determine the effect of dual bifurcation stenting on hemodynamic parameters known to influence restenosis and thrombosis. We hypothesized that double stenting, especially with a longer side branch (SB) stent, likely has a negative effect on wall shear stress (WSS), WSS gradient (WSSG), and oscillatory shear index (OSI). To test this hypothesis, we developed computational models of dual stents at bifurcations and non-Newtonian blood simulations. The models were then interfaced, meshed, and solved in a validated finite-element package. Longer and shorter stents at the SB and provisional stenting were compared. It was found that stents placed in the SB at a bifurcation lowered WSS, but elevated WSSG and OSI. Dual stenting with longer SB stent had the most adverse impact on SB endothelial WSS, WSSG, and OSI, with low WSS region up to 50% more than the case with shorter SB stent. The simulations also demonstrated flow disturbances resulting from SB stent struts protruding into the main flow field near the carina, which may have implications on stent thrombosis. The simulations predict a negative hemodynamic role for SB stenting, which is exaggerated with a longer stent, consistent with clinical trial findings that dual-stenting is comparable or inferior to provisional stenting.
Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats
Authors: Laughlin M. Harold , Padilla Jaume , Jenkins Nathan T. , Thorne Pamela K. , Martin Jeffrey S. , Rector R. Scott , Akter Sadia , Davis J. Wade
Published: July 2015

Using next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology we assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles of Otsuka Long Evans Tokushima Fatty (OLETF) rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). We hypothesized that the greatest effects of exercise would be in the gastrocnemius arterioles. Results show that EX caused the largest number of changes in gene expression in the soleus and white gastrocnemius 2a arterioles with little to no changes in the feed arteries. In contrast, SPRINT caused substantial changes in gene expression in the feed arteries. IPA canonical pathway analysis revealed 18 pathways with significant changes in gene expression when analyzed across vessels and revealed that EX induces increased expression of the following genes in all arterioles examined: Shc1, desert hedgehog protein (Dhh), adenylate cyclase 4 (Adcy4), G protein binding protein, alpha (Gnat1), and Bcl2l1 and decreased expression of ubiquitin D (Ubd) and cAMP response element modulator (Crem). EX increased expression of endothelin converting enzyme (Ece1), Hsp90b, Fkbp5, and Cdcl4b in four of five arterioles. SPRINT had effects on expression of Crem, Dhh, Bcl2l1, and Ubd that were similar to EX. SPRINT also increased expression of Nfkbia, Hspa5, Tubb 2a and Tubb 2b, and Fkbp5 in all five arterioles and increased expression of Gnat1 in all but the soleus second-order arterioles. Many contractile and/or structural protein genes were increased by SPRINT in the gastrocnemius feed artery, but the same genes exhibited decreased expression in red gastrocnemius arterioles. We conclude that training-induced changes in arteriolar gene expression patterns differ by muscle fiber type composition and along the arteriolar tree.
Exercise training causes differential changes in gene expression in diaphragm arteries and 2A arterioles of obese rats
Authors: Laughlin M. Harold , Padilla Jaume , Jenkins Nathan T. , Thorne Pamela K. , Martin Jeffrey S. , Rector R. Scott , Akter Sadia , Davis J. Wade
Published: July 2015

We employed next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology to assess the effects of two different exercise training protocols on transcriptional profiles in diaphragm second-order arterioles (D2a) and in the diaphragm feed artery (DFA) from Otsuka Long Evans Tokushima Fatty (OLETF) rats. Arterioles were isolated from the diaphragm of OLETF rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). Our hypothesis was that exercise training would have similar effects on gene expression in the diaphragm and soleus muscle arterioles because diaphragm blood flow increases during exercise to a similar extent as in soleus. Results reveal that several canonical pathways that were significantly altered by exercise in limb skeletal muscles were not among the pathways significantly changed in the diaphragm arterioles including actin cytoskeleton signaling, role of NFAT in regulation of immune response, protein kinase A signaling, and protein ubiquitination pathway. EX training altered the expression of a smaller number of genes than did SPRINT in the DFA but induced a larger number of genes with altered expression in the D2a than did SPRINT. In fact, FDR differential expression analysis (FDR, 10%) indicated that only two genes exhibited altered expression in D2a of SPRINT rats. Very few of the genes that exhibited altered expression in the DFA or D2a were also altered in limb muscle arterioles. Finally, results indicate that the 2a arterioles of soleus muscle (S2a) from endurance-trained animals and the DFA of SPRINT animals exhibited the largest number of genes with altered expression.
Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity
Authors: Donia Marco , Andersen Rikke , Kjeldsen Julie W. , Fagone Paolo , Munir Shamaila , Nicoletti Ferdinando , Andersen Mads Hald , thor Straten Per , Svane Inge Marie
Published: July 2015

In the absence of a local inflammatory response, expression of MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive expression of MHC class II. In a set of primary melanoma cell populations and correspondingly expanded autologous tumor-infiltrating lymphocytes (TIL), we show how MHC class II expression on melanoma cells associates with strong MHC class II–restricted CD4+ T-cell responses that are specific for tumors. Notably, we found that tumor-specific CD4+ T-cell responses were dominated by TNF production. TNF reduced CD8+ T-cell activation in IFNγ-rich environments resembling a tumor site. Conversely, direct CD4+ T-cell responses had no influence on either the proliferation or viability of melanoma cells. Taken together, our results illustrate a novel immune escape mechanism that can be activated by aberrant expression of MHC class II molecules, which by attracting tumor-specific CD4+ T cells elicit a local inflammatory response dominated by TNF that, in turn, inhibits cytotoxic CD8+ T-cell responses Cancer Res; 75(18); 3747–59. ©2015 AACR.
Serum Calcium and Serum Albumin Are Biomarkers That Can Discriminate Malignant from Benign Pelvic Masses
Authors: Kelly Michael G. , Winkler Stuart S. , Lentz Samuel S. , Berliner Steve H. , Swain Melissa F. , Skinner Halcyon G. , Schwartz Gary G.
Published: July 2015

Background: Biomarkers that aid in the differential diagnosis of malignant pelvic masses from benign ones prior to surgery are needed in order to triage women with malignant masses to appropriate specialist care. Because high albumin-adjusted serum calcium predicted ovarian cancer among women without evidence of disease, we hypothesized that it might predict cancer among women with pelvic masses that were evident radiographically.

Methods: We studied a cohort of 514 women with pelvic masses who underwent resection at Wake Forest University Baptist Medical Center from July 2009 through June 2013. We divided patients into a “training” set, to identify associations in the data, and a “testing” set, to confirm them. Data were obtained from medical records. A best fit model was selected using the Akaike Information Criterion.

Results: Albumin-adjusted serum calcium was significantly higher in women with malignant versus benign masses (P = 0.0004). High normocalcemia, i.e., an albumin-adjusted serum calcium ≥ 10 mg/dL, occurred in 53% of women with malignant tumors versus 12% of benign tumors. High normocalcemia was associated with an approximately 14-fold increased risk of malignancy. The best fit model (Overa) included albumin, calcium, and nonlinear terms. Overa achieved an area under the curve of 0.83 with a sensitivity of 72% and specificity of 83%, a positive predictive value of 71% and a negative predictive value of 85%.

Conclusions: A model using serum calcium and serum albumin to predict malignancy in women with pelvic masses has high sensitivity and is economical.

Impact: Our model can help triage women with ovarian cancer to appropriate surgical care. Cancer Epidemiol Biomarkers Prev; 24(10); 1593–8. ©2015 AACR.
Tumor-Related Molecular Mechanisms of Oxaliplatin Resistance
Authors: Martinez-Balibrea Eva , Martínez-Cardús Anna , Ginés Alba , Ruiz de Porras Vicenç , Moutinho Catia , Layos Laura , Manzano José Luis , Bugés Cristina , Bystrup Sara , Esteller Manel , Abad Albert
Published: July 2015

Oxaliplatin was the first platinum drug with proven activity against colorectal tumors, becoming a standard in the management of this malignancy. It is also considered for the treatment of pancreatic and gastric cancers. However, a major reason for treatment failure still is the existence of tumor intrinsic or acquired resistance. Consequently, it is important to understand the molecular mechanisms underlying the appearance of this phenomenon to find ways of circumventing it and to improve and optimize treatments. This review will be focused on recent discoveries about oxaliplatin tumor-related resistance mechanisms, including alterations in transport, detoxification, DNA damage response and repair, cell death (apoptotic and nonapoptotic), and epigenetic mechanisms. Mol Cancer Ther; 14(8); 1767–76. ©2015 AACR.
IL6 Mediates Immune and Colorectal Cancer Cell Cross-talk via miR-21 and miR-29b
Authors: Patel Saroor A.A. , Gooderham Nigel J.
Published: July 2015

Tumors are surrounded and infiltrated by a variety of stromal cell types, including fibroblasts, immune cells, and vascular endothelial cells, which interact with malignant cells to generate the tumor microenvironment (TME). This complex environment is thought to be regulated by the tumor in order to promote its survival and progression and thus constitutes a potential target for cancer therapy. However, intercellular communication within the microenvironment is not yet well understood. The current study investigates the mechanism by which cancer and immune cells communicate using an in vitro coculture model. It is demonstrated that IL6, a proinflammatory cytokine, secreted by immune cells promotes colorectal cancer cell invasiveness. In addition, in the presence of IL6, the cancer cells were able to secrete circulating miRNAs miR-21 and miR-29b to further induce immune cell IL6 production. Activated immune cells were also found to release miR-21 into the TME. Taken together, these mechanistic findings provide a better understanding of intercellular communication between immune and cancer cells in the TME and offer insight into some of the key players that mediate this cross-talk.

Implications: This study demonstrates that cocultured cancer and immune cells communicate via IL6 and circulating miRNAs to sustain chronic inflammation and promote prometastatic cancer cell behavior. In addition, critical players are identified that mediate intercellular communication in the TME and suggest possible therapeutic approaches that target the microenvironment. Mol Cancer Res; 13(11); 1502–8. ©2015 AACR.
Long-Term Functional, Cosmetic and Sexual Outcomes of Hypospadias Correction Performed in Childhood
Authors: Thiry S. , Saussez T. , Dormeus S. , Tombal B. , Wese F.X. , Feyaerts A.
Published: July 2015

Objective: Hypospadias surgery, especially when performed early in life, may have a significant impact on the urinary and sexual functions in an adult. Because the literature is still limited, this paper assesses long-term functional, cosmetic and sexual results of hypospadias repair performed in childhood. Patients and Methods: The study includes 275 patients older than 12 years treated for a hypospadias by an Onlay, Mathieu, Duplay, or Duckett's technique between January 1990 and December 2000. Flowmetry results were retrospectively obtained from patients' charts. The Paediatric Penile Perception Score (PPPS), the Hypospadias Objective Scoring Evaluation (HOSE) and the IIEF-5 score (when older than 16 years old) questionnaires were used to assess cosmetic and sexual results. The PPPS is designed to assess both penile self-perception with regard to meatus, glans, skin and general appearance. The HOSE is a five-point scoring system designed to allow an objective appraisal of the outcome of hypospadias repair, based on evaluating meatal location, meatal shape, urinary stream, straightness of erection, and the presence and complexity of any complicating urethral fistula. Results: Qmax were within age-adjusted references, independent of the surgical technique, with median (range) Qmax of 18.8 ml/s (range 3-45, n = 136). Patients expressed a high satisfaction for every single item of the penile perception scale (PPPS), with mean values between 2 (satisfied) and 3 (very satisfied). Eighty-two percent were satisfied or very satisfied of the overall evaluation of penile appearance. Eighty-one percent of patients had a normal erectile function (IIEF-5 >22; n = 35/43). Conclusions: Taking into account the limitation of a small number of patients resulting from a low 21% questionnaire's response rate, the results of this study align with previous reports from the literature and confirms that hypospadias repair using standard techniques results in acceptable functional, cosmetic and sexual outcomes. This study highlights the need of developing a set of standard approved outcomes assessments tools for evaluating the long-term impact of hypospadias repair performed in infancy.
Release of Cell-Free Ice Nucleators from Three Recombinant Ice+Zymomonas mobilis Strains
Authors: Varsaki Athanasia , Perisynakis Angelos , Drainas Constantin
Published: July 2015

Background/Aims: This work is a study of the ability of three recombinant Zymomonas mobilis strains to release ice nucleators into their growth medium. Methods: The recombinant ice+Z. mobilis cells were tested for their ability to produce cell-free ice nucleators, under three different growth temperatures and three different glucose concentrations. Results: Cell-free ice nucleators were obtained from all the recombinant ice+Z. mobilis cells tested. The cell-free ice nucleation activity was not affected by the glucose concentration in the growth medium or the growth temperature. The freezing temperature threshold was below -7.6°C, demonstrating a class C nucleating structure of the ice nucleation protein. The size of the ice nucleators was less than 0.22 μm and their density was estimated as 1.024 ± 0.004 g/ml by Percoll density centrifugation. The properties of the detected ice nucleators, in addition to the absence of pyruvate decarboxylase activity in the spent medium (a cytosolic marker), support that the cell-free ice nucleation activity was due to the extracellular release of ice nucleators. Conclusion: These findings indicate that the recombinant ice+Z. mobilis cells could be valuable for future use as a source of active cell-free ice nucleation protein.
Prevalence of Spinal Cord Injury in Iran: A 3-Source Capture-Recapture Study
Authors: Jazayeri Seyed Behzad , Ataeepour Mehdi , Rabiee Helale , Motevalian Seyed Abbas , Saadat Soheil , Vaccaro Alexander R. , Rahimi-Movaghar Vafa
Published: July 2015

Background: Epidemiologic data of spinal cord injured (SCI) patients are necessary for prevention policymaking and improvement of social and healthcare support to patients. This study was designed to estimate the prevalence of traumatic and non-traumatic SCI in Iran in a three-source capture-recapture study. Methods: Three organizations, which provide supports to SCI patients were identified. Demographic data of patients in each organization was obtained. Datasets were formed and matching data were found. Matched data were incorporated into STATA 12 for log linear analyses. Results of sensitivity analyses were used to estimate total number of SCI patients in Iran. Veterans of Iraq-Iran conflict were added as separate data source to final results. Results: The prevalence of traumatic and non-traumatic SCI patients is 296.87 (95% confidence intervals (CI): 292.04-302.48) per million in Tehran and Alborz provinces. The prevalence of SCI in Iran is an estimated 318.45 (95% CI: 312.98-324.54) per million. Conclusion: The prevalence of SCI in Iran is among the lowest figures reported in the literature. The supporting organizations in Iran do not have details about the cause, level and severity of SCI patients. A national study to register SCI patients' data is needed.
Weight Loss, Dietary Intake and Pulse Wave Velocity
Authors: Petersen Kristina , Blanch Natalie , Keogh Jennifer , Clifton Peter
Published: July 2015

We have recently conducted a meta-analysis to determine the effect of weight loss achieved by an energy-restricted diet with or without exercise, anti-obesity drugs or bariatric surgery on pulse wave velocity (PWV) measured at all arterial segments. Twenty studies, including 1,259 participants, showed that modest weight loss (8% of the initial body weight) caused a reduction in PWV measured at all arterial segments. However, due to the poor methodological design of the included studies, the results of this meta-analysis can only be regarded as hypothesis generating and highlight the need for further research in this area. In the future, well-designed randomised controlled trials are required to determine the effect of diet-induced weight loss on PWV and the mechanisms involved. In addition, there is observational evidence that dietary components such as fruit, vegetables, dairy foods, sodium, potassium and fatty acids may be associated with PWV, although evidence from well-designed intervention trials is lacking. In the future, the effect of concurrently improving dietary quality and achieving weight loss should be assessed in randomised controlled trials.