bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol Loading Reprograms the MicroRNA-143/145–Myocardin Axis to Convert Aortic Smooth Muscle Cells to a Dysfunctional Macrophage-Like Phenotype
Authors: Vengrenyuk Yuliya , Nishi Hitoo , Long Xiaochun , Ouimet Mireille , Savji Nazir , Martinez Fernando O. , Cassella Courtney P. , Moore Kathryn J. , Ramsey Stephen A. , Miano Joseph M. , Fisher Edward A. 
Published: January 2015

Objective—
We previously showed that cholesterol loading in vitro converts mouse aortic vascular smooth muscle cells (VSMC) from a contractile state to one resembling macrophages. In human and mouse atherosclerotic plaques, it has become appreciated that ≈40% of cells classified as macrophages by histological markers may be of VSMC origin. Therefore, we sought to gain insight into the molecular regulation of this clinically relevant process.

Approach and Results—
VSMC of mouse (or human) origin were incubated with cyclodextrin–cholesterol complexes for 72 hours, at which time the expression at the protein and mRNA levels of contractile-related proteins was reduced and of macrophage markers increased. Concurrent was downregulation of miR-143/145, which positively regulate the master VSMC differentiation transcription factor myocardin. Mechanisms were further probed in mouse VSMC. Maintaining the expression of myocardin or miR-143/145 prevented and reversed phenotypic changes caused by cholesterol loading. Reversal was also seen when cholesterol efflux was stimulated after loading. Notably, despite expression of macrophage markers, bioinformatic analyses showed that cholesterol-loaded cells remained closer to the VSMC state, consistent with impairment in classical macrophage functions of phagocytosis and efferocytosis. In apoE-deficient atherosclerotic plaques, cells positive for VSMC and macrophage markers were found lining the cholesterol-rich necrotic core.

Conclusions—
Cholesterol loading of VSMC converts them to a macrophage-appearing state by downregulating the miR-143/145–myocardin axis. Although these cells would be classified by immunohistochemistry as macrophages in human and mouse plaques, their transcriptome and functional properties imply that their contributions to atherogenesis would not be those of classical macrophages.
Systems Biology With High-Throughput Sequencing Reveals Genetic Mechanisms Underlying the Metabolic Syndrome in the Lyon Hypertensive Rat
Authors: Wang Jinkai , Ma Man Chun John , Mennie Amanda K. , Pettus Janette M. , Xu Yang , Lin Lan , Traxler Matthew G. , Jakoubek Jessica , Atanur Santosh S. , Aitman Timothy J. , Xing Yi , Kwitek Anne E. 
Published: January 2015

Background—
The metabolic syndrome (MetS) is a collection of co-occurring complex disorders including obesity, hypertension, dyslipidemia, and insulin resistance. The Lyon hypertensive and Lyon normotensive rats are models of MetS sensitivity and resistance, respectively. To identify genetic determinants and mechanisms underlying MetS, an F2 intercross between Lyon hypertensive and Lyon normotensive was comprehensively studied.

Methods and Results—

Multidimensional data were obtained including genotypes of 1536 single-nucleotide polymorphisms, 23 physiological traits, and >150 billion nucleotides of RNA-seq reads from the livers of F2 intercross offspring and parental rats. Phenotypic and expression quantitative trait loci (eQTL) were mapped. Application of systems biology methods identified 17 candidate MetS genes. Several putative causal
cis
-eQTL were identified corresponding with phenotypic QTL loci. We found an eQTL hotspot on rat chromosome 17 that is causally associated with multiple MetS-related traits and found
RGD1562963
, a gene regulated in
cis
by this eQTL hotspot, as the most likely eQTL driver gene directly affected by genetic variation between Lyon hypertensive and Lyon normotensive rats.

Conclusions—
Our study sheds light on the intricate pathogenesis of MetS and demonstrates that systems biology with high-throughput sequencing is a powerful method to study the pathogenesis of complex genetic diseases.
Redescription of Palaemon antennarius H. Milne Edwards, 1837 and Palaemon migratorius (Heller, 1862) (Crustacea, Decapoda, Palaemonidae) and description of two new species of the genus from the circum-Mediterranean area
Authors: TZOMOS THEODOROS , KOUKOURAS ATHANASIOS 
Published: January 2015

Palaemon antennarius H. Milne Edwards, 1837 and Palaemon migratorius (Heller, 1862) are redescribed and differentiated from other circum-Mediterranean members of the genus on the basis of the following characters: (a) lack of mandibular palp, (b) form of first maxilliped endites, (c) form of maxillula palp, (d) number and length of plumose setae at the distal end of telson, and (e) shape of the fifth abdominal pleuron. In addition, two new species of the genus, P. colossus sp. nov. and P. minos sp. nov., are described from Rhodes and Crete, respectively. The new species are distinguished from the hitherto known congeners by the following set of key characters: (a) shape of the fifth abdominal pleuron, (b) number and length of the plumose setae at the distal end of the telson, (c) shape of the endopod of the first pleopod, (d) form of thoracic and abdominal sternal armature and (e) number of the lanceolate setae on the ventral margins of telson.
Uncertainties of Temperature Measurements on Snow-Covered Land and Sea Ice from In Situ and MODIS Data during BROMEX
Authors: Hall Dorothy K. , Nghiem Son V. , Rigor Ignatius G. , Miller Jeffrey A. 
Published: January 2015

AbstractThe Bromine, Ozone, and Mercury Experiment (BROMEX) was conducted in March and April of 2012 near Barrow, Alaska, to investigate impacts of Arctic sea ice reduction on chemical processes. During BROMEX, multiple sensors were deployed to measure air and surface temperature. The uncertainties in temperature measurement on snow-covered land and sea ice surfaces were examined using in situ data and temperature measurements that were derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) and are part of the Terra and Aqua ice-surface temperature and land-surface temperature (LST) standard data products. Following an ~24-h cross-calibration study, two Thermochrons (small temperature-sensing devices) were deployed at each of three field sites: a sea ice site in the Chukchi Sea, a mixed-cover site, and a homogeneous tundra site. At each site, one Thermochron was shielded from direct sunlight and one was left unshielded, and they were placed on top of the snow or ice. The best agreement between the Thermochron- and MODIS-derived temperatures was found between the shielded Thermochrons and the Aqua MODIS LSTs, with an average agreement of 0.6° ± 2.0°C (sample size of 84) at the homogeneous tundra site. The results highlight some uncertainties associated with obtaining consistent air and surface temperature measurements in the harsh Arctic environment, using both in situ and satellite sensors. It is important to minimize uncertainties that could introduce biases in long-term temperature trends.
Increasing the Skill of Probabilistic Forecasts: Understanding Performance Improvements from Model-Error Representations
Authors: Berner J. , Fossell K. R. , Ha S.-Y. , Hacker J. P. , Snyder C. 
Published: January 2015

Abstract
Four model-error schemes for probabilistic forecasts over the contiguous United States with the WRF-ARW mesoscale ensemble system are evaluated in regard to performance. Including a model-error representation leads to significant increases in forecast skill near the surface as measured by the Brier score. Combining multiple model-error schemes results in the best-performing ensemble systems, indicating that current model error is still too complex to be represented by a single scheme alone.
To understand the reasons for the improved performance, it is examined whether model-error representations increase skill merely by increasing the reliability and reducing the bias—which could also be achieved by postprocessing—or if they have additional benefits.
Removing the bias results overall in the largest skill improvement. Forecasts with model-error schemes continue to have better skill than without, indicating that their benefit goes beyond bias reduction.
Decomposing the Brier score into its components reveals that, in addition to the spread-sensitive reliability, the resolution component is significantly improved. This indicates that the benefits of including a model-error representation go beyond increasing reliability. This is further substantiated when all forecasts are calibrated to have similar spread. The calibrated ensembles with model-error schemes consistently outperform the calibrated control ensemble.
Including a model-error representation remains beneficial even if the ensemble systems are calibrated and/or debiased. This suggests that the merits of model-error representations go beyond increasing spread and removing the mean error and can account for certain aspects of structural model uncertainty.
Predictability of Persistent Thailand Rainfall during the Mature Monsoon Season in 2011 Using Statistical Downscaling of CGCM Seasonal Prediction
Authors: Imada Yukiko , Kanae Shinjiro , Kimoto Masahide , Watanabe Masahiro , Ishii Masayoshi 
Published: January 2015

Abstract
Predictability of above-normal rainfall over Thailand during the rainy season of 2011 was investigated with a one-tier seasonal prediction system based on an atmosphere–ocean coupled general circulation model (CGCM) combined with a statistical downscaling method. The statistical relationship was derived using singular value decomposition analysis (SVDA) between observed regional rainfall and the hindcast of tropical sea surface temperature (SST) from the seasonal prediction system, which has an ability to forecast oceanic variability for lead times up to several months. The downscaled product of 2011 local rainfall was obtained by combining rainfall patterns derived from significant modes of SVDA. This method has the advantage in terms of flexibility that phenomenon-based statistical relationships, such as teleconnections associated with El Niño–Southern Oscillation (ENSO), Indian Ocean dipole (IOD), or the newly recognized central Pacific El Niño, are considered separately in each SVDA mode. The downscaled prediction initialized from 1 August 2011 reproduced the anomalously intense precipitation pattern over Indochina including northern Thailand during the latter half of the rainy season, even though the direct hindcast from the CGCM failed to predict the local rainfall distribution and intensity. Further analysis revealed that this method is applicable to the other recent events such as heavy rainfall during the rainy seasons of 2002 and 2008 in Indochina.
The Use of Cryotherapy for Papilloma and Early Laryngeal Cancers
Authors: Benninger Michael S. , Derakhshan Adeeb , Milstein Claudio F. 
Published: January 2015

Study Design: Retrospective chart review. Objective: To determine the efficacy of adjuvant cryotherapy in the treatment of early glottic cancer and laryngeal papillomatosis. Summary of Background Data: The use of cryotherapy in conjunction with traditional modalities has recently been proposed to improve voice outcomes in patients with early laryngeal cancer as compared to pretreatment conditions. This study investigates its utility in improving oncological outcomes and decreasing recurrences of laryngeal papillomatosis. Methods: Patients with either early glottic cancer or laryngeal papillomatosis that received cryotherapy as part of their surgical regimen were investigated. All patients were seen at a large tertiary care center within a 10-year window. Demographic data were collected and all postoperative notes were reviewed. Recurrences of the laryngeal cancer were noted, as was the duration of time between successive papillomatosis operations. Results: The charts of 54 glottic cancer and 29 papillomatosis patients that received cryotherapy were reviewed. One patient from the papillomatosis cohort was excluded from statistical analysis due to lack of follow-up. Overall, 16 (30%) of the laryngeal cancer patient experienced a malignant recurrence. The overall 5-year survival of these patients was 98% and the 5-year disease-free survival was 74%. The use of adjuvant cryotherapy in the treatment of laryngeal papillomatosis extended the duration of time between surgeries by an average of 79 days ( P = .23). Conclusion: The use of adjuvant cryotherapy in the treatment of early glottic cancer does not improve the rate of carcinoma recurrences. Additionally, cryotherapy does not result in a statistically significant increase in the duration of disease-free period for laryngeal papillomatosis patients, although the observed increase may be clinically important.
Consistent Ipsilateral Development of the Posterior Extension of the Quadrangular Cartilage and Bony Spur Formation in Nasal Septal Deviation
Authors: Saedi Babak , Rashan Ali R. , Lipan Michael , Nayak Jayakar V. , Most Sam P. 
Published: January 2015

ObjectiveSeptal spurs are exceedingly common structural deformities that contribute to nasal obstruction and often require surgical correction. The posterior extension of the quadrangular cartilage (PEQC) and its relationship with septal spurs have not been previously examined. We seek to examine the anatomic and histologic relationship of the PEQC and concurrent septal spurs in patients undergoing septoplasty.Study DesignProspective cohort study.SettingFacial plastic and rhinology center in tertiary hospital setting.Subject and MethodsThirty patients with septal deviation are described in this series. The quadrangular cartilage and associated septal spur were removed en bloc from patients undergoing septoplasty. The length of the PEQC, the side of spur deviation, and the relationship of the PEQC to the spur (ipsilateral vs contralateral) were recorded.ResultsThe mean length of the PEQC, beyond the bony‐cartilaginous junction, was 30.06 ± 6.06 mm. The PEQC was present on the ipsilateral side of the spur deviation in all 30 patients (100%).ConclusionAt sites of septal spur formation, the quadrangular cartilage possesses an average 3‐cm extension beyond its junction with the bony components of the septum. This cartilaginous extension is exclusively found on the same side of spur deviation. These findings have implications on our understanding of the ontogeny of commonly found septal spurs and deviations, as well as treatment strategies and cartilage graft harvesting.
Comparison of Hybrid Laryngotracheal Reconstruction to Traditional Single‐ and Double‐Stage Laryngotracheal Reconstruction
Authors: Raol Nikhila , Rogers Derek , Setlur Jennifer , Hartnick Christopher J. 
Published: January 2015

Objectives(1) To describe outcomes from and modifications to the hybrid laryngotracheal reconstruction (LTR) technique and (2) to compare this technique to traditional single‐ and double‐stage LTR (ssLTR/dsLTR).Study DesignChart review with case series.SettingTertiary care otolaryngology specialty hospital.SubjectsAll patients under 18 years of age who underwent LTR by a single surgeon from July 1, 2009, to December 31, 2013.MethodsCharts were assessed for age, gender, etiology of stenosis, type of reconstruction, comorbidities, length of stay, complications, and tracheostomy status. Analysis was performed using Kruskal‐Wallis and Wilcoxon rank sum analysis.ResultsForty‐four patients were identified, with 13 hybrid LTRs, 27 ssLTRs, and 4 dsLTRs. Of the hybrid LTRs, an overall decannulation rate of 76.9% was noted, comparable to those for dsLTR. The hybrid LTR technique offered a significantly shorter period of narcotic use when compared to ssLTR (median 15 vs 21 days, P <. 01). No patients in the hybrid LTR group developed supraglottic granulation tissue. There was no statistically significant difference in median length of stay for ssLTRs, dsLTRs, and hybrid LTRs (P =. 38).ConclusionThe hybrid LTR technique is well tolerated and useful in patients of all ages. Narcotics can be weaned more quickly due to the presence of a secure airway at all times via the existing tracheostomy. Use of a long stent prevents formation of granulation tissue that may be seen with a suprastomal stent. This technique should be considered in patients with high‐grade stenosis with a preexisting tracheostomy.
CT characteristics in 24 patients with POEMS syndrome
Authors: Shi Xiaofeng , Hu Shudong , Luo Xianfu , Luo Ming , You Haiyan , Zhu Yan , Xi Xiaodong 
Published: January 2015

Background POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes) syndrome is a complicated and rare disease. Systematic research on computed tomography (CT) imaging characteristics in POEMS syndrome is scanty. The role of CT in diagnosis needs to be assessed. Purpose To retrospectively analyze the CT imaging features in 24 patients with POEMS syndrome and evaluate the role of CT in diagnosis of this disease. Material and Methods Twenty-four patients with confirmed POEMS syndrome were included in the study. Chest and abdominal CT images were analyzed. Results The three minor diagnostic criteria for POEMS syndrome (extravascular volume overload, organomegaly, and bone lesions) can be detected effectively by CT. Extravascular volume overload involved multiple serous cavities: hydrothorax, hydropericardium, and ascites, which were found in 79.2%, 41.7%, and 54.2% patients, respectively. The volume of effusion was small to moderate. Organomegaly involved multiorgans: hepatomegaly was found in 45.8% patients, splenomegaly in 54.2%, and lymphadenopathy in 75% patients. Hepatospleen exhibited moderate homogeneous enlargement without local enhanced signal after injection of contrast material. Bone lesions were classified into three groups: osteosclerotic, osteolytic, and mixed lesions. Osteosclerotic lesions, taking multiple, scattered, and variably sized high-density plaque-like appearance, were found in 20.8% patients. Osteolytic lesions, exhibiting punched-out low-density image, were found in 4.2% patients. Mixed ones, holding both common characteristics of them, were detected in 8.3% patients. These CT abnormalities disappeared after effective treatment. Conclusion CT plays vital role in the confirmation of the three minor diagnostic criteria for POEMS syndrome: extravascular volume overload, organomegaly, and bone lesions.
Clinical significance of CD44s, CD44v3 and CD44v6 in breast cancer
Authors: Wu Xiao-Jin , Li Xiao-Dong , Zhang Hanze , Zhang Xiaofei , Ning Zhong-Hua , Yin Yong-Mei , Tian Ye 
Published: January 2015

Objectives To evaluate levels of CD44 standard variant (CD44s), CD44 variant exon 3 (CD44v3) and CD44 variant exon 6 (CD44v6) protein in breast cancer tissue, and investigate their relationships with clinicopathological characteristics of the disease. Methods Immunohistochemistry for CD44s, CD44v3 and CD44v6 was retrospectively performed on formalin-fixed paraffin wax-embedded breast cancer tissue samples. Results Tumour tissue samples from 60 patients with breast cancer were included. There was a significant relationship between CD44s positivity and tumour diameter and lymph node involvement. CD44v6 positivity was significantly associated with tumour–node–metastasis (TNM) stage and lymph node involvement. There were significant negative correlations between CD44s immunopositivity, tumour diameter and TNM stage, and significant positive correlations between CD44v6 immunopositivity, tumour diameter and TNM stage. Conclusions CD44s and CD44v6 appear to play opposing roles in the development of breast cancer, but their precise functions and mechanisms of action remain unclear.
A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine
Authors: Neri Monica , Frustaci Alessandra , Milic Mirta , Valdiglesias Vanessa , Fini Massimo , Bonassi Stefano , Barbanti Piero 
Published: January 2015

Background Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. Methods Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. Results Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65–2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. Conclusions The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels.
Sleep and chronobiology in cluster headache
Authors: Barloese M , Lund N , Petersen A , Rasmussen M , Jennum P , Jensen R 
Published: January 2015

Background and aim M.R. present address: PAIN, National Institutes of Health, Bethesda, MD, USA Cluster headache (CH) is the headache disorder with the strongest chronobiological traits. The severe attacks of pain occur with diurnal and annual rhythmicity but the precise rhythm and involvement of potential zeitgebers is unknown. Patients complain of poor sleep quality yet this has never been studied. We investigated triggers, rhythms, sleep quality and chronotypes in CH. Methods Patients and controls completed questionnaires and structured interviews composed of new and previously validated parts including the Pittsburgh Sleep Quality Index (PSQI) and Morningness-Eveningness Questionnaire (MEQ). Patients were characterized by a CH index, a unified measure of headache burden. Results A total of 275 CH patients and 145 matched controls were included. The most common trigger was sleep (80%) and a relationship between clusters and daylight was identified. Of the patients, 82.2% reported diurnal and 56% annual rhythmicity. Patients reported impaired sleep quality (PSQI) ( p < 0.0001) and an inverse relationship between time passed since last attack and sleep quality was identified ( p < 0.0001). The CH index was positively related to the PSQI ( p < 0.0001). Conclusion Diurnally, CH exhibits a relationship with night-time and annually with daylight hours. Patients’ sleep quality is reduced compared with controls. Results suggest a complex relationship as sleep quality improves between clusters, but remains pathological.
Can nitric oxide induce migraine in normal individuals?
Authors: Olesen Jes , Ashina Messoud 
Published: January 2015

Introduction For many years, scientists have debated the possibility that an individual “migraine threshold” determines the likelihood with which individuals may express migraine attacks. Discussion Recent discoveries provided evidence for both genetic and environmental influences on individual migraine expression. The question is whether any person may express a migraine attack given a sufficiently strong stimulus or provocation. Here, we reviewed and discussed the ability of nitric oxide to induce migraine-like attacks in normal individuals. Conclusion Experimental data show that normal individuals may develop a migraine-like attack and that the human data point to different ways of further developing existing animal and human models.