bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemoprevention of Squamous Cell Carcinoma of the Head and Neck: No Time to Lose Momentum
Authors: Wirth Lori J. 
Published: January 2014

AbstractThe prospects for chemoprevention to reduce the incidence of squamous cell carcinoma of the head and neck (SCCHN) are great. The tissue at risk for harboring disease is relatively accessible for examination and biopsy. Patients appropriate for study can be easily identified by their risk factors and the presence of premalignant lesions. Our understanding of the pathogenesis of SCCHN is ever increasing, and offers new opportunities to explore strategies for prevention therapies. In this issue of Cancer Prevention Research, Saba and colleagues report on a phase Ib trial of celecoxib plus erlotinib to prevent progression to higher-grade dysplasia or invasive carcinoma in patients with oral premalignant lesions. The overall response rate was 57%, though by the time of last analysis, 85% of patients relapsed. In this commentary, challenges to the success of chemoprevention clinical trials for SCCHN, such as pitfalls in using surrogate biomarkers and reversal of histologic premalignant changes as study endpoints, are discussed. In addition, strategies to help ensure further development in the field of head and neck cancer prevention are reviewed. These include focusing efforts on tobacco cessation and human papillomavirus vaccination, targeting key molecular drivers of head and neck carcinogenesis, and focusing on combination strategies that have the potential to eradicate premalignant clones, even if some toxicity is encountered. Cancer Prev Res; 7(3); 279–82. ©2014 AACR.
Antiangiogenic Therapy Inhibits Venous Thrombus Resolution
Authors: Evans Colin E. , Grover Steven P. , Humphries Julia , Saha Prakash , Patel Anant P. , Patel Ashish S. , Lyons Oliver T. , Waltham Matt , Modarai Bijan , Smith Alberto 
Published: January 2014

Objective—
Venous thromboembolism is a common complication in patients with cancer, resulting in significant morbidity and mortality. Clinical studies suggest that the incidence of venous thromboembolic events increased after treatment of these patients with antiangiogenic agents. Thrombi resolve through a process of remodeling, involving the formation of microvascular channels within the thrombus. Our aim was to determine whether inhibiting angiogenesis affects venous thrombus resolution.

Approach and Results—

Thrombus was induced in the inferior vena cava of mice. These mice were treated with axitinib (50 mg/kg per day), 2-methoxyestradiol (2ME, 150 mg/kg per day), or vehicle control. Thrombus size, recanalization, neovascularization, inflammatory cell content, and collagen content were assessed after axitinib (days 3, 10, 17) and 2ME (day 10 only) treatment (n=6/group). Axitinib treatment resulted in reduced thrombus resolution (
P
<0.002) and vein recanalization (
P
<0.001) compared with vehicle-treated controls. This was associated with inhibition of organization as seen through reduced thrombus neovascularization (
P
<0.0001) and collagen (
P
<0.0001) content, as well as reduced macrophage accumulation in the thrombus (
P
<0.001). Treatment with a second antiangiogenic agent, 2ME, mirrored these findings, with a similar order of magnitude of effect of treatment over vehicle control in all of the parameters measured, with the exception of neutrophil content, which was significantly reduced after 2ME treatment but not affected by axitinib.

Conclusions—
Antiangiogenic therapy (using axitinib and 2ME) inhibits the resolution of venous thrombi, which could lead to persistent venous obstruction and the possibility of thrombus extension. This potential prolongation of venous occlusion by antiangiogenic agents should therefore be taken into consideration in trials of these agents and when managing the complications of venous thromboembolic events in patients with cancer.
Hurricane Eyewall Evolution in a Forced Shallow-Water Model
Authors: Hendricks Eric A. , Schubert Wayne H. , Chen Yu-Han , Kuo Hung-Chi , Peng Melinda S. 
Published: January 2014

Abstract
A forced shallow-water model is used to understand the role of diabatic and frictional effects in the generation, maintenance, and breakdown of the hurricane eyewall potential vorticity (PV) ring. Diabatic heating is parameterized as an annular mass sink of variable width and magnitude, and the nonlinear evolution of tropical storm–like vortices is examined under this forcing. Diabatic heating produces a strengthening and thinning PV ring in time due to the combined effects of the mass sink and radial PV advection by the induced divergent circulation. If the forcing makes the ring thin enough, then it can become dynamically unstable and break down into polygonal asymmetries or mesovortices. The onset of barotropic instability is marked by simultaneous drops in both the maximum instantaneous velocity and minimum pressure, consistent with unforced studies. However, in a sensitivity test where the heating is proportional to the relative vorticity, universal intensification occurs during barotropic instability, consistent with a recent observational study. Friction is shown to help stabilize the PV ring by reducing the eyewall PV and the unstable-mode barotropic growth rate. The radial location and structure of the heating is shown to be of critical importance for intensity variability. While it is well known that it is critical to heat in the inertially stable region inside the radius of maximum winds to spin up the hurricane vortex, these results demonstrate the additional importance of having the net heating as close as possible to the center of the storm, partially explaining why tropical cyclones with very small eyes can rapidly intensify to high peak intensities.
Traumatic intrathoracic tracheobronchial injuries: A study of 78 cases
Authors: Alassal Mohamed A , Ibrahim Bedir M , Elsadeck Nabil 
Published: January 2014

Background: Tracheobronchial injuries are encountered with increasing frequency because of improvements in pre-hospital care. We reviewed our experience of these injuries to determine how to better recognize them and facilitate their correct management. Methods: Patients with traumatic non-iatrogenic intrathoracic tracheobronchial injuries managed in 2 tertiary centers in Saudi Arabia between 2000 and 2012, were studied. Clinical presentation, diagnostic evaluation, management, and outcome were reviewed. Results: 78 patients with tracheobronchial injuries were included in this study. They were divided into 2 groups according to the management strategy. Forty-seven patients who were managed conservatively, and 31 underwent surgery. Surgery allowed shorter intensive care unit and hospital stays; otherwise, the results were comparable between the two groups. Conclusions: Early recognition and expedient appropriate management are essential in these potentially lethal injuries. Operative management can be achieved with acceptable mortality, and conservative treatment should be considered as a valuable alternative to the well-established surgical treatment.
Nutraceuticals in the prophylaxis of pediatric migraine: Evidence-based review and recommendations
Authors: Orr Serena L , Venkateswaran Sunita 
Published: January 2014

Introduction The literature on complementary and alternative medicine (CAM) is expanding. One of the most common conditions for which CAM is studied in the pediatric population is migraine. Nutraceuticals are a form of CAM that is being used for pediatric migraine prophylaxis. Methods A literature search was carried out in order to identify both observational studies and randomized controlled trials on the use of nutraceuticals for the prophylaxis of pediatric migraine. Adult studies on included nutraceuticals were also reviewed. Review Thirty studies were reviewed on six different nutraceuticals: butterbur, riboflavin, ginkgolide B, magnesium, coenzyme Q10 and polyunsaturated fatty acids. Conclusion Overall, the quality of the evidence for the use of nutraceuticals in pediatric migraine prophylaxis is poor. Further research needs to be done in order to study the efficacy of nutraceuticals for the prophylaxis of pediatric migraine.
Familial hemiplegic migraine treated by sodium valproate and lamotrigine
Authors: Pelzer Nadine , Stam Anine H , Carpay Johannes A , Vries Boukje de , van den Maagdenberg Arn MJM , Ferrari Michel D , Haan Joost , Terwindt Gisela M 
Published: January 2014

Background Familial hemiplegic migraine (FHM) is a rare monogenic subtype of migraine with aura that includes motor auras. Prophylactic treatment of FHM often has marginal effects and involves a trial-and-error strategy based on therapeutic guidelines for non-hemiplegic migraine and on case reports in FHM. Methods We assessed the response to prophylactic medication in an FHM family and sequenced the FHM2 ATP1A2 gene in all available relatives. Results A novel p.Met731Val ATP1A2 mutation was identified. Attack frequency was reduced significantly with sodium valproate monotherapy ( n = 1) and attacks ceased completely with a combination of sodium valproate and lamotrigine ( n = 2). Conclusions We report dramatic prophylactic effects of sodium valproate and lamotrigine in an FHM2 family, making these drugs worth considering in the treatment of other FHM patients.
Development and refinement of new statistical methods for enhanced syndromic surveillance during the 2012 Olympic and Paralympic Games
Authors: Morbey Roger A , Elliot Alex J , Charlett Andre , Andrews Nick , Verlander Neville Q , Ibbotson Sue , Smith Gillian E 
Published: January 2014

Prior to the 2012 London Olympic and Paralympic Games, new statistical methods had to be developed for the enhanced syndromic surveillance during the Games. Different methods were developed depending on whether or not historical data were available. Practical solutions were needed to cope with the required daily reporting and data quality issues. During the Games, nearly 4800 signals were tested on average each day, generating statistical alarms that were assessed to provide information on areas of potential public health concern and reassurance that no major adverse incident had occurred. Graphical abstract
Anterior Cruciate Ligament Reconstruction Rehabilitation
Authors: Wright Rick W. , Haas Amanda K. , Anderson Joy , Calabrese Gary , Cavanaugh John , Hewett Timothy E. , Lorring Dawn , McKenzie Christopher , Preston Emily , Williams Glenn ,   the MOON Group, Amendola Annunziato , Andrish Jack T. , Brophy Robert H. , Cox Charles L. , Dunn Warren R. , Flanigan David C. , Hettrich Carolyn M. , Huston Laura J. , Jones Morgan H. , Kaeding Christopher C. , Lattermann Christian , Magnussen Robert A. , Marx Robert G. , Matava Matthew J. , McCarty Eric C. , Parker Richard D. , Reinke Emily K. , Smith Matthew V. , Spindler Kurt P. , Vidal Armando F. , Wolcott Michelle L. , Wolf Brian R. 
Published: January 2014

Context: Anterior cruciate ligament (ACL) reconstruction rehabilitation has evolved over the past 20 years. This evolution has been driven by a variety of level 1 and level 2 studies. Evidence Acquisition: The MOON Group is a collection of orthopaedic surgeons who have developed a prospective longitudinal cohort of the ACL reconstruction patients. To standardize the management of these patients, we developed, in conjunction with our physical therapy committee, an evidence-based rehabilitation guideline. Study Design: Clinical review. Level of Evidence: Level 2. Results: This review was based on 2 systematic reviews of level 1 and level 2 studies. Recently, the guideline was updated by a new review. Continuous passive motion did not improve ultimate motion. Early weightbearing decreases patellofemoral pain. Postoperative rehabilitative bracing did not improve swelling, pain range of motion, or safety. Open chain quadriceps activity can begin at 6 weeks. Conclusion: High-level evidence exists to determine appropriate ACL rehabilitation guidelines. Utilizing this protocol follows the best available evidence.
The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects
Authors: Colucci Giuseppe , Stutz Monika , Rochat Sophie , Conte Tiziana , Pavicic Marko , Reusser Marianne , Giabbani Evelyne , Huynh Anh , Thürlemann Charles , Keller Peter , Alberio Lorenzo 
Published: January 2014

Key PointsDDAVP is the drug of choice for mild hemophilia A and von Willebrand disease and (by unclear mechanisms) for platelet function disorders. In vivo DDAVP selectively and markedly enhances the ability to form procoagulant platelets by enhancing intracellular Na+ and Ca2+ fluxes.
Tracing retinal vessel trees by transductive inference
Authors: De Jaydeep , Li Huiqi , Cheng Li 
Published: January 2014

Abstract

Background
Structural study of retinal blood vessels provides an early indication of diseases such as diabetic retinopathy, glaucoma, and hypertensive retinopathy. These studies require accurate tracing of retinal vessel tree structure from fundus images in an automated manner. However, the existing work encounters great difficulties when dealing with the crossover issue commonly-seen in vessel networks.

Results
In this paper, we consider a novel graph-based approach to address this tracing with crossover problem: After initial steps of segmentation and skeleton extraction, its graph representation can be established, where each segment in the skeleton map becomes a node, and a direct contact between two adjacent segments is translated to an undirected edge of the two corresponding nodes. The segments in the skeleton map touching the optical disk area are considered as root nodes. This determines the number of trees to-be-found in the vessel network, which is always equal to the number of root nodes. Based on this undirected graph representation, the tracing problem is further connected to the well-studied transductive inference in machine learning, where the goal becomes that of properly propagating the tree labels from those known root nodes to the rest of the graph, such that the graph is partitioned into disjoint sub-graphs, or equivalently, each of the trees is traced and separated from the rest of the vessel network. This connection enables us to address the tracing problem by exploiting established development in transductive inference. Empirical experiments on public available fundus image datasets demonstrate the applicability of our approach.

Conclusions
We provide a novel and systematic approach to trace retinal vessel trees with the present of crossovers by solving a transductive learning problem on induced undirected graphs.
Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals
Authors: Uesaka Masahiro , Nishimura Osamu , Go Yasuhiro , Nakashima Kinichi , Agata Kiyokazu , Imamura Takuya 
Published: January 2014

Abstract

Background
The majority of non-coding RNAs (ncRNAs) involved in mRNA metabolism in mammals have been believed to downregulate the corresponding mRNA expression level in a pre- or post-transcriptional manner by forming short or long ncRNA-mRNA duplex structures. Information on non-duplex-forming long ncRNAs is now also rapidly accumulating. To examine the directional properties of transcription at the whole-genome level, we performed directional RNA-seq analysis of mouse and chimpanzee tissue samples.

Results
We found that there is only about 1% of the genome where both the top and bottom strands are utilized for transcription, suggesting that RNA-RNA duplexes are not abundantly formed. Focusing on transcription start sites (TSSs) of protein-coding genes revealed that a significant fraction of them contain switching-points that separate antisense- and sense-biased transcription, suggesting that head-to-head transcription is more prevalent than previously thought. More than 90% of head-to-head type promoters contain CpG islands. Moreover, CCG and CGG repeats are significantly enriched in the upstream regions and downstream regions, respectively, of TSSs located in head-to-head type promoters. Genes with tissue-specific promoter-associated ncRNAs (pancRNAs) show a positive correlation between the expression of their pancRNA and mRNA, which is in accord with the proposed role of pancRNA in facultative gene activation, whereas genes with constitutive expression generally lack pancRNAs.

Conclusions
We propose that single-stranded ncRNA resulting from head-to-head transcription at GC-rich sequences regulates tissue-specific gene expression.
Integrated transcriptome analysis of mouse spermatogenesis
Authors: Margolin Gennady , Khil Pavel P , Kim Joongbaek , Bellani Marina A , Camerini-Otero R Daniel 
Published: January 2014

Abstract

Background
Differentiation of primordial germ cells into mature spermatozoa proceeds through multiple stages, one of the most important of which is meiosis. Meiotic recombination is in turn a key part of meiosis. To achieve the highly specialized and diverse functions necessary for the successful completion of meiosis and the generation of spermatozoa thousands of genes are coordinately regulated through spermatogenesis. A complete and unbiased characterization of the transcriptome dynamics of spermatogenesis is, however, still lacking.

Results
In order to characterize gene expression during spermatogenesis we sequenced eight mRNA samples from testes of juvenile mice from 6 to 38 days post partum. Using gene expression clustering we defined over 1,000 novel meiotically-expressed genes. We also developed a computational de-convolution approach and used it to estimate cell type-specific gene expression in pre-meiotic, meiotic and post-meiotic cells. In addition, we detected 13,000 novel alternative splicing events around 40% of which preserve an open reading frame, and found experimental support for 159 computational gene predictions. A comparison of RNA polymerase II (Pol II) ChIP-Seq signals with RNA-Seq coverage shows that gene expression correlates well with Pol II signals, both at promoters and along the gene body. However, we observe numerous instances of non-canonical promoter usage, as well as intergenic Pol II peaks that potentially delineate unannotated promoters, enhancers or small RNA clusters.

Conclusions
Here we provide a comprehensive analysis of gene expression throughout mouse meiosis and spermatogenesis. Importantly, we find over a thousand of novel meiotic genes and over 5,000 novel potentially coding isoforms. These data should be a valuable resource for future studies of meiosis and spermatogenesis in mammals.
Genome sequence of Anopheles sinensis provides insight into genetics basis of mosquito competence for malaria parasites
Authors: Zhou Dan , Zhang Donghui , Ding Guohui , Shi Linna , Hou Qing , Ye Yuting , Xu Yang , Zhou Huayun , Xiong Chunrong , Li Shengdi , Yu Jing , Hong Shanchao , Yu Xinyou , Zou Ping , Chen Chen , Chang Xuelian , Wang Weijie , Lv Yuan , Sun Yan , Ma Lei , Shen Bo , Zhu Changliang 
Published: January 2014

Abstract

Background

Anopheles sinensis is an important mosquito vector of Plasmodium vivax, which is the most frequent and widely distributed cause of recurring malaria throughout Asia, and particularly in China, Korea, and Japan.

Results
We performed 454 next-generation sequencing and obtained a draft sequence of A. sinensis assembled into scaffolds spanning 220.8 million base pairs. Analysis of this genome sequence, we observed expansion and contraction of several immune-related gene families in anopheline relative to culicine mosquito species. These differences suggest that species-specific immune responses to Plasmodium invasion underpin the biological differences in susceptibility to Plasmodium infection that characterize these two mosquito subfamilies.

Conclusions
The A. sinensis genome produced in this study, provides an important resource for analyzing the genetic basis of susceptibility and resistance of mosquitoes to Plasmodium parasites research which will ultimately facilitate the design of urgently needed interventions against this debilitating mosquito-borne disease.
Massive deregulation of miRNAs from nuclear reprogramming errors during trophoblast differentiation for placentogenesis in cloned pregnancy
Authors: Hossain Md Munir , Tesfaye Dawit , Salilew-Wondim Dessie , Held Eva , Pröll Maren J , Rings Franca , Kirfel Gregor , Looft Christian , Tholen Ernst , Uddin Jasim , Schellander Karl , Hoelker Michael 
Published: January 2014

Abstract

Background
Low efficiency of Somatic Cell Nuclear Transfer (NT) has been widely addressed with high incidence of placental abnormalities due to genetic and epigenetic modifications. MiRNAs are shown to be major regulators of such modifications. The present study has been carried out to identify the expression patterns of 377 miRNAs, their functional associations and mechanism of regulation in bovine placentas derived from artificial insemination (AI), in vitro production (IVP) and NT pregnancies.

Results
This study reveals a massive deregulation of miRNAs as chromosomal cluster or miRNA families without sex-linkage in NT and in-vitro derived IVP placentas. Cell specific localization miRNAs in blastocysts and expression profiling of embryos and placentas at different developmental stages identified that the major deregulation of miRNAs exhibited in placentas at day 50 of pregnancies is found to be less dependent on global DNA methylation, rather than on aberrant miRNA biogenesis molecules. Among them, aberrant AGO2 expression due to hypermethylation of its promoter was evident. Along with other factors, aberrant AGO2 expression was observed to be associated with multiple defects in trophoblast differentiation through deregulation of miRNAs mediated mechanisms.

Conclusion
These aberrant miRNA activities might be associated with genetic and epigenetic modifications in abnormal placentogenesis due to maldifferentiation of early trophoblast cell lineage in NT and IVP pregnancies. This study provides the first insight into genome wide miRNA expression, their role in regulation of trophoblast differentiation as well as abnormal placental development in Somatic Cell Nuclear Transfer pregnancies to pave the way to improve the efficiency of cloning by nuclear transfer.