bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smooth Muscle Cell Deletion of Low-Density Lipoprotein Receptor–Related Protein 1 Augments Angiotensin II–Induced Superior Mesenteric Arterial and Ascending Aortic Aneurysms
Authors: Davis Frank M. , Rateri Debra L. , Balakrishnan Anju , Howatt Deborah A. , Strickland Dudley K. , Muratoglu Selen C. , Haggerty Christopher M. , Fornwalt Brandon K. , Cassis Lisa A. , Daugherty Alan 
Published: November 2014

Objective—
Low-density lipoprotein receptor–related protein 1 (LRP1), a multifunctional protein involved in endocytosis and cell signaling pathways, leads to several vascular pathologies when deleted in vascular smooth muscle cells (SMCs). The purpose of this study was to determine whether LRP1 deletion in SMCs influenced angiotensin II–induced arterial pathologies.

Approach and Results—

LRP1 protein abundance was equivalent in selected arterial regions, but SMC-specific LRP1 depletion had no effect on abdominal and ascending aortic diameters in young mice. To determine the effects of LRP1 deficiency on angiotensin II vascular responses, SMC-specific LRP1 (smLRP1
+/+
) and smLRP1-deficient (smLRP1
−/−
) mice were infused with saline, angiotensin II, or norepinephrine. Several smLRP
−/−
mice died of superior mesenteric arterial (SMA) rupture during angiotensin II infusion. In surviving mice, angiotensin II profoundly augmented SMA dilation in smLRP1
−/−
mice. SMA dilation was blood pressure dependent as demonstrated by a similar response during norepinephrine infusion. SMA dilation was also associated with profound macrophage accumulation, but minimal elastin fragmentation. Angiotensin II infusion led to no significant differences in abdominal aorta diameters between smLRP1
+/+
and smLRP1
−/−
mice. In contrast, ascending aortic dilation was exacerbated markedly in angiotensin II–infused smLRP1
−/−
mice, but norepinephrine had no significant effect on either aortic region. Ascending aortas of smLRP1
−/−
mice infused with angiotensin II had minimal macrophage accumulation but significantly increased elastin fragmentation and mRNA abundance of several LRP1 ligands including MMP-2 (matrix metalloproteinase-2) and uPA (urokinase plasminogen activator).

Conclusions—

smLRP1 deficiency had no effect on angiotensin II–induced abdominal aortic aneurysm formation. Conversely, angiotensin II infusion in smLRP1
−/−
mice exacerbated SMA and ascending aorta dilation. Dilation in these 2 regions had differential association with blood pressure and divergent pathological characteristics.
Mortality From Thoracic Aortic Diseases and Associations With Cardiovascular Risk Factors
Authors: Sidloff David , Choke Edward , Stather Philip , Bown Matthew , Thompson John , Sayers Robert 
Published: November 2014

Background—
Temporal trends in mortality from thoracic aortic disease are unclear. This study examined trends in mortality from thoracic aortic aneurysm (TAA) and aortic dissection (AD) with the aim of identifying associations with trends in established cardiovascular risk factors.

Methods and Results—

TAA and AD mortality (1994–2010) using
International Classification of Diseases
codes was extracted from the World Health Organization mortality database and age standardized. World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Eighteen World Health Organization member states were included (Europe=13, Australasia=2, North America=2, Asia=1). Ecological regression was performed of temporal trends in cardiovascular risk factors (1946–2010) and independent correlations to mortality trends. TAA and AD mortality trends show substantial heterogeneity but are generally declining. TAA mortality has increased in Hungary, Romania, Japan, and Denmark, and AD mortality has increased in Romania and Japan; therefore, the mortality decline is not universal. A linear relationship exists between trends in systolic blood pressure, cholesterol, and body mass index and mortality from TAA. Body mass index demonstrated a negative linear association with female AD mortality, whereas trends in systolic blood pressure demonstrated a positive linear relationship with male AD mortality. Trends in smoking prevalence were not associated with TAA or AD mortality trends.

Conclusions—
This population-level ecological regression provides evidence that mortality secondary to TAA and mortality secondary to AD are both in decline. Differences between countries could be explained by population-level changes in common cardiovascular risk factors. Public health measures could further reduce mortality from TAA and AD.
Transnasal Endoscopic Treatment of Orbital Complications of Acute Sinusitis
Authors: Teinzer Fabian , Stammberger Heinz , Tomazic Peter Valentin 
Published: November 2014

Objective: Orbital complications of acute sinusitis can be severe. Nowadays, surgical drainage of intraorbital abscess formations is performed endoscopically in the majority of cases. This study aims to illustrate the Graz experience in the endoscopic treatment of orbital complications and to present our treatment algorithm. Methods: In a retrospective study, 53 patients were examined who were referred to the Department of General Otorhinolaryngology of the ENT-University Hospital Graz from 2000 to 2011. Results: Of 53 patients, men were affected more frequently than women (n = 37, 69.81% vs n = 16, 30.19%). The following diagnoses were obtained: 9 preseptal cellulitis, 7 orbital cellulitis, 14 subperiosteal abscesses, and 23 orbital abscesses. In 16 patients, a conservative therapy was administered; 37 patients underwent surgery, most of them purely endoscopically (n = 31, 83.78%). Two of the patients who underwent conservative treatment and 7 of those who underwent surgery experienced a recurrence (n = 9, 16.98%). Conclusion: Based on analysis of our recurrences, we have tried to create the optimal treatment algorithm as a point of reference in the management of orbital complications of acute sinusitis. In this way, 7 of 9 recurrences could have been avoided, equaling a hypothetical recurrence rate of 3.77% instead of 16.98% (hypothetical success rate 96.23%).
Predicting Depression and Quality of Life among Long‐term Head and Neck Cancer Survivors
Authors: Moubayed Sami P. , Sampalis John S. , Ayad Tareck , Guertin Louis , Bissada Eric , Gologan Olguta E. , Soulières Denis , Lambert Louise , Filion Edith , Nguyen‐Tan Phuc Felix , Christopoulos Apostolos 
Published: November 2014

ObjectiveThe aim of this study is to identify clinical factors that are predictive of depression and quality of life (QOL) among long‐term survivors of head and neck squamous cell carcinoma and to develop predictive scores using these factors.Study DesignCohort studySettingTertiary referral center.Subjects and MethodsA total of 209 posttreatment (median follow‐up, 38.7 months) head and neck cancer patients were prospectively evaluated using the Hospital Anxiety Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, and the EORTC Quality of Life Questionnaire Head and Neck 35, and pretreatment patient‐related, tumor‐related, and treatment‐related predictors were identified using chart review. Bivariate (χ2 and t test) and multivariate (linear regression) analyses were used to construct predictive models.ResultsSignificant pretreatment predictors of depression were identified on multivariate analysis as smoking at diagnosis, >14 alcoholic drinks per week, T3 or T4 status, and >3 medications (P <. 001). Two or more of these factors yielded an 82.3% sensitivity in detecting significant depressive symptoms (defined as a HADS cutoff score of 5). Significant predictors of fatigue, global health/QOL, social contact, speech, pain, swallowing, and xerostomia were also identified.ConclusionPretreatment predictors of long‐term depression and QOL have been defined using multivariate models, and an easily applicable predictive score of long‐term depression is proposed. Potential eventual clinical applications include prophylactic intervention in at‐risk patients.
Myocardial performance is impaired in patients with branch retinal vein occlusion
Authors: Kaderli Berkant , Kaderli Aysel Aydin , Gullulu Sumeyye , Inan Umit Ubeyt , Senturk Tunay , Aydinlar Ali , Yucel Ahmet Ali , Avci Remzi 
Published: November 2014

Objective To investigate whether the Tei index, which is an indicator of global myocardial function and an independent predictor of cardiac death, is increased in patients with branch retinal vein occlusion (BRVO). Methods The Tei index was used to evaluate myocardial performance, in addition to conventional echocardiographic evaluation of myocardial structural and functional changes, in patients with BRVO, patients with hypertension and healthy controls. Results Out of 36 patients with BRVO (18 female, 18 male; 17 hypertensive, 19 normotensive), 29 patients with hypertension (15 female, 14 male) and 28 healthy controls (15 female, 13 male), there were no significant between-group differences in age and sex. The mitral A wave was higher and mitral E/A ratio, mitral E wave and ejection time were lower, in patients with BRVO than in healthy controls. Mean Tei index was significantly higher in the BRVO group than in patients with hypertension or healthy controls. Compared with healthy controls, the Tei index was significantly higher in hypertensive and normotensive patients with BRVO. Conclusion Myocardial performance is decreased in patients with BRVO, independent of whether or not they have hypertension.
Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator
Authors: Kameda Takuro , Shide Kotaro , Yamaji Takumi , Kamiunten Ayako , Sekine Masaaki , Taniguchi Yasuhiro , Hidaka Tomonori , Kubuki Yoko , Shimoda Haruko , Marutsuka Kousuke , Sashida Goro , Aoyama Kazumasa , Yoshimitsu Makoto , Harada Taku , Abe Hiroo , Miike Tadashi , Iwakiri Hisayoshi , Tahara Yoshihiro , Sueta Mitsue , Yamamoto Shojiro , Hasuike Satoru , Nagata Kenji , Iwama Atsushi , Kitanaka Akira , Shimoda Kazuya 
Published: November 2014

Key Points
Loss of TET2 accelerates the degree of malignancy of MPNs in combination with JAK2V617F. Loss of TET2 sustains MPNs in combination with JAK2V617F.
ATL response to arsenic/interferon therapy is triggered by SUMO/PML/RNF4-dependent Tax degradation
Authors: Dassouki Zeina , Sahin Umut , El Hajj Hiba , Jollivet Florence , Kfoury Youmna , Lallemand-Breitenbach Valérie , Hermine Olivier , de Thé Hugues , Bazarbachi Ali 
Published: November 2014

Key Points
Survival of ATL cells depends on continuous Tax expression. Arsenic/interferon combination induces SUMO/PML/RNF4-mediated Tax degradation.
How we treat chronic graft-versus-host disease
Authors: Flowers Mary E. D. , Martin Paul J. 
Published: November 2014

Abstract
Chronic graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The 2-year cumulative incidence of chronic GVHD requiring systemic treatment is ∼30% to 40% by National Institutes of Health criteria. The risk of chronic GVHD is higher and the duration of treatment is longer after HCT with mobilized blood cells than with marrow cells. Clinical manifestations can impair activities of daily living and often linger for years. Hematology and oncology specialists who refer patients to centers for HCT are often subsequently involved in the management of chronic GVHD when patients return to their care after HCT. Treatment of these patients can be optimized under shared care arrangements that enable referring physicians to manage long-term administration of immunosuppressive medications and supportive care with guidance from transplant center experts. Keys to successful collaborative management include early recognition in making the diagnosis of chronic GVHD, comprehensive evaluation at the onset and periodically during the course of the disease, prompt institution of systemic and topical treatment, appropriate monitoring of the response, calibration of treatment intensity over time in order to avoid overtreatment or undertreatment, and the use of supportive care to prevent complications and disability.
Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia
Authors: Stieglitz Elliot , Troup Camille B. , Gelston Laura C. , Haliburton John , Chow Eric D. , Yu Kristie B. , Akutagawa Jon , Taylor-Weiner Amaro N. , Liu Y. Lucy , Wang Yong-Dong , Beckman Kyle , Emanuel Peter D. , Braun Benjamin S. , Abate Adam , Gerbing Robert B. , Alonzo Todd A. , Loh Mignon L. 
Published: November 2014

Key PointsMutations in SETBP1 can be detected using droplet digital polymerase chain reaction in at least 30% of patients with JMML and are associated with a dismal prognosis. Patients harboring rare cells with mutant SETBP1 at diagnosis should be considered candidates for swift hematopoietic stem cell transplant.
Serum 25-hydroxyvitamin D levels and lung function in adults with asthma: the HUNT Study
Authors: Larose Tricia L. , Langhammer Arnulf , Chen Yue , Camargo Carlos A. , Romundstad Pål , Mai Xiao-Mei 
Published: November 2014

The association between vitamin D status and lung function in adults with asthma remains unclear.We studied this cross-sectional association and possible modification by sex and allergic rhinitis in 760 adults (aged 19–55 years) with self-reported asthma in the Nord-Trøndelag Health Study. Serum 25-hydroxyvitamin D (25(OH)D) level <50 nmol·L−1was considered deficient. Lung function measurements included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % predicted and FEV1/FVC ratio. Multiple linear regression models were used to estimate adjusted regression coefficients (β) and 95% confidence intervals.44% of asthma adults had serum 25(OH)D levels <50 nmol·L−1. Its associations with lung function measures seemed to be modified by sex and allergic rhinitis (p<0.03 for three-way interaction term). Overall, a serum 25(OH)D level <50 nmol·L−1was not associated with lung function measurements in subjects with allergic rhinitis in this asthma cohort. In men with asthma but without allergic rhinitis, however, a serum 25(OH)D level <50 nmol·L−1was significantly associated with lower FEV1/FVC ratio (β=−8.60%; 95% CI: −16.95%– −0.25%).Low serum 25(OH)D level was not associated with airway obstruction in most asthma adults with the exception of men with asthma but without allergic rhinitis.
CMOS-compatible metal-stabilized nanostructured Si as anodes for lithium-ion microbatteries
Authors: Lee Gibaek , Schweizer Stefan L , Wehrspohn Ralf B 
Published: November 2014

Abstract
The properties of fully complementary metal-oxide semiconductor (CMOS)-compatible metal-coated nanostructured silicon anodes for Li-ion microbatteries have been studied. The one-dimensional nanowires on black silicon (nb-Si) were prepared by inductively coupled plasma (ICP) etching and the metal (Au and Cu) coatings by successive magnetron sputtering technique. The Cu-coated nb-Si show the most promising electrochemical performance enhancements for the initial specific capacity as well as their cyclability compared to pristine nb-Si. The electrochemical and microstructural properties before and after cycling of the metal-coated nb-Si compared to their pristine counterparts are discussed in detail.
The associations of leg lean mass with foot pain, posture and function in the Framingham foot study
Authors: McLean Robert R , Dufour Alyssa B , Katz Patricia P , Hillstrom Howard J , Hagedorn Thomas J , Hannan Marian T 
Published: November 2014

AbstractBackgroundFoot disorders are common in older adults and associated with impaired lower extremity function. Reduced muscle mass may play a role in the etiology of foot disorders and consequent poor function.MethodsWe examined the association of leg lean mass with foot pain, posture and function among 1,795 individuals (mean age 67 years) from the population‐based Framingham Foot Study (2002‐2008). Pain was assessed via questionnaire, and a pressure mat classified foot posture (arch: high, low, referent) during standing and function (pronation, supination, referent) during gait. Leg lean mass was measured by whole body dual energy x‐ray absorptiometry.ResultsIn age‐ and body mass index‐adjusted logistic (pain) and multinomial logistic (posture, function) regression models, a 1‐standard deviation increase in leg lean mass was associated with lower odds of foot pain (OR = 0.76, 95% CI: 0.68, 0.86) and pronation (OR = 0.76, 95% CI: 0.67, 0.85), and higher odds of supination (OR = 1.17, 95% CI: 1.04, 1.31). Adjustment for sex attenuated these associations. Higher leg lean mass was associated with lower odds of high arch, even after adjustment for sex (OR = 0.73, 95% CI: 0.60, 0.89).ConclusionsThough not related to foot pain or function, reduced leg lean mass was associated with extreme foot posture in older adults. Loss of muscle mass with aging may thus play a role in the etiology of functional impairment due to foot disorders.
Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis
Authors: Wynne James W , Shiell Brian J , Marsh Glenn A , Boyd Victoria , Harper Jennifer A , Heesom Kate , Monaghan Paul , Zhou Peng , Payne Jean , Klein Reuben , Todd Shawn , Mok Lawrence , Green Diane , Bingham John , Tachedjian Mary , Baker Michelle L , Matthews David , Wang Lin-Fa 
Published: November 2014

Abstract
Background
Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV).

Results
The host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death.

Conclusions
This is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis.
Genomic epidemiology of a protracted hospital outbreak caused by multidrug-resistant Acinetobacter baumanniiin Birmingham, England
Authors: Halachev Mihail R , Chan Jacqueline Z-M , Constantinidou Chrystala I , Cumley Nicola , Bradley Craig , Smith-Banks Matthew , Oppenheim Beryl , Pallen Mark J 
Published: November 2014

Abstract
Background
Multidrug-resistant Acinetobacter baumannii commonly causes hospital outbreaks. However, within an outbreak, it can be difficult to identify the routes of cross-infection rapidly and accurately enough to inform infection control. Here, we describe a protracted hospital outbreak of multidrug-resistant A. baumannii, in which whole-genome sequencing (WGS) was used to obtain a high-resolution view of the relationships between isolates.

Methods
To delineate and investigate the outbreak, we attempted to genome-sequence 114 isolates that had been assigned to the A. baumannii complex by the Vitek2 system and obtained informative draft genome sequences from 102 of them. Genomes were mapped against an outbreak reference sequence to identify single nucleotide variants (SNVs).

Results
We found that the pulsotype 27 outbreak strain was distinct from all other genome-sequenced strains. Seventy-four isolates from 49 patients could be assigned to the pulsotype 27 outbreak on the basis of genomic similarity, while WGS allowed 18 isolates to be ruled out of the outbreak. Among the pulsotype 27 outbreak isolates, we identified 31 SNVs and seven major genotypic clusters. In two patients, we documented within-host diversity, including mixtures of unrelated strains and within-strain clouds of SNV diversity. By combining WGS and epidemiological data, we reconstructed potential transmission events that linked all but 10 of the patients and confirmed links between clinical and environmental isolates. Identification of a contaminated bed and a burns theatre as sources of transmission led to enhanced environmental decontamination procedures.

Conclusions
WGS is now poised to make an impact on hospital infection prevention and control, delivering cost-effective identification of routes of infection within a clinically relevant timeframe and allowing infection control teams to track, and even prevent, the spread of drug-resistant hospital pathogens.
Linking hypothetical knowledge patterns to disease molecular signatures for biomarker discovery in Alzheimer’s disease
Authors: Malhotra Ashutosh , Younesi Erfan , Bagewadi Shweta , Hofmann-Apitius Martin 
Published: November 2014

Abstract
Background
A number of compelling candidate Alzheimer’s biomarkers remain buried within the literature. Indeed, there should be a systematic effort towards gathering this information through approaches that mine publicly available data and substantiate supporting evidence through disease modeling methods. In the presented work, we demonstrate that an integrative gray zone mining approach can be used as a way to tackle this challenge successfully.

Methods
The methodology presented in this work combines semantic information retrieval and experimental data through context-specific modeling of molecular interactions underlying stages in Alzheimer’s disease (AD). Information about putative, highly speculative AD biomarkers was harvested from the literature using a semantic framework and was put into a functional context through disease- and stage-specific models. Staging models of AD were further validated for their functional relevance and novel biomarker candidates were predicted at the mechanistic level.

Results
Three interaction models were built representing three stages of AD, namely mild, moderate, and severe stages. Integrated analysis of these models using various arrays of evidence gathered from experimental data and published knowledge resources led to identification of four candidate biomarkers in the mild stage. Mode of action of these candidates was further reasoned in the mechanistic context of models by chains of arguments. Accordingly, we propose that some of these ‘emerging’ potential biomarker candidates have a reasonable mechanistic explanation and deserve to be investigated in more detail.

Conclusions
Systematic exploration of derived hypothetical knowledge leads to generation of a coherent overview on emerging knowledge niches. Integrative analysis of this knowledge in the context of disease mechanism is a promising approach towards identification of candidate biomarkers taking into consideration the complex etiology of disease. The added value of this strategy becomes apparent particularly in the area of biomarker discovery for neurodegenerative diseases where predictive biomarkers are desperately needed.